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Won Bae Kim  (Kim WB) 95 Articles
Thyroid
Big Data Articles (National Health Insurance Service Database)
Recent Changes in the Incidence of Thyroid Cancer in Korea between 2005 and 2018: Analysis of Korean National Data
Yun Mi Choi, Jiwoo Lee, Mi Kyung Kwak, Min Ji Jeon, Tae Yong Kim, Eun-Gyoung Hong, Won Bae Kim, Won Gu Kim
Endocrinol Metab. 2022;37(5):791-799.   Published online October 11, 2022
DOI: https://doi.org/10.3803/EnM.2022.1533
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AbstractAbstract PDFPubReader   ePub   CrossRef-TDMCrossref - TDM
Background
In this study, we evaluated the recent changes in the standardized, age-specific, stage-specific incidence rates (IRs) of thyroid cancer in Korea and compared them with the incidence data reported by the Surveillance, Epidemiology, and End Results Program.
Methods
The analysis was conducted using the incidence data (2005 to 2018) from the Statistics Korea and Korea Central Cancer Registry.
Results
The age-standardized IR (SIR) of thyroid cancer increased from 24.09 per 100,000 in 2005 to 74.83 in 2012 (annual percent change [APC], 14.5). From 2012 to 2015, the SIR decreased to 42.52 (APC, –17.9) and then remained stable until 2018 (APC, 2.1). This trend was similar in both men and women. Regarding age-specific IRs, the IRs for ages of 30 years and older showed a trend similar to that of the SIR; however, for ages below 30 years, no significant reduction was observed from the vertex of IR in 2015. Regarding stage-specific IRs, the increase was more prominent in those with regional disease (APC, 17.4) than in those with localized disease until 2012; then, the IR decreased until 2015 (APC, –16.1). The average APC from 2005 to 2018 increased in men, those under the age of 30 years, and those with regional disease.
Conclusion
The SIR in Korea peaked in 2012 and decreased until 2015 and then remained stable until 2018. However, in young individuals under the age of 30 years, the IR did not significantly decrease but tended to increase again. In terms of stage-specific IRs, the sharpest increase was seen among those with regional disease.
Miscellaneous
Active Surveillance as an Effective Management Option for Low-Risk Papillary Thyroid Microcarcinoma
Min Ji Jeon, Won Gu Kim, Tae Yong Kim, Young Kee Shong, Won Bae Kim
Endocrinol Metab. 2022;37(1):180-180.   Published online February 28, 2022
DOI: https://doi.org/10.3803/EnM.2022.103
Corrects: Endocrinol Metab 2021;36(4):717
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  • Lateral Involvement in Different Sized Papillary Thyroid Carcinomas Patients with Central Lymph Node Metastasis: A Multi-Center Analysis
    Yu Heng, Zheyu Yang, Pengyu Cao, Xi Cheng, Lei Tao
    Journal of Clinical Medicine.2022; 11(17): 4975.     CrossRef
Miscellaneous
Protocol for a Korean Multicenter Prospective Cohort Study of Active Surveillance or Surgery (KoMPASS) in Papillary Thyroid Microcarcinoma
Min Ji Jeon, Yea Eun Kang, Jae Hoon Moon, Dong Jun Lim, Chang Yoon Lee, Yong Sang Lee, Sun Wook Kim, Min-Hee Kim, Bo Hyun Kim, Ho-Cheol Kang, Minho Shong, Sun Wook Cho, Won Bae Kim
Endocrinol Metab. 2022;37(1):181-182.   Published online February 28, 2022
DOI: https://doi.org/10.3803/EnM.2022.104
Corrects: Endocrinol Metab 2021;36(2):359
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Thyroid
Clinical Characteristics and Prognosis of Coexisting Thyroid Cancer in Patients with Graves’ Disease: A Retrospective Multicenter Study
Jee Hee Yoon, Meihua Jin, Mijin Kim, A Ram Hong, Hee Kyung Kim, Bo Hyun Kim, Won Bae Kim, Young Kee Shong, Min Ji Jeon, Ho-Cheol Kang
Endocrinol Metab. 2021;36(6):1268-1276.   Published online November 26, 2021
DOI: https://doi.org/10.3803/EnM.2021.1227
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  • 4 Citations
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   CrossRef-TDMCrossref - TDM
Background
The association between Graves’ disease (GD) and co-existing thyroid cancer is still controversial and most of the previously reported data have been based on surgically treated GD patients. This study investigated the clinicopathological findings and prognosis of concomitant thyroid cancer in GD patients in the era of widespread application of ultrasonography.
Methods
Data of GD patients who underwent thyroidectomy for thyroid cancer between 2010 and 2019 in three tertiary hospitals in South Korea (Asan Medical Center, Chonnam National University Hwasun Hospital, and Pusan National University Hospital) were collected and analyzed retrospectively. In the subgroup analysis, aggressiveness and clinical outcomes of thyroid cancer were compared nodular GD and non-nodular GD groups according to the presence or absence of the thyroid nodules other than thyroid cancer (index nodules).
Results
Of the 15,159 GD patients treated at the hospitals during the study period, 262 (1.7%) underwent thyroidectomy for coexisting thyroid cancer. Eleven patients (4.2%) were diagnosed with occult thyroid cancer and 182 patients (69.5%) had microcarcinomas. No differences in thyroid cancer aggressiveness, ultrasonographic findings, or prognosis were observed between the nodular GD and non-nodular GD groups except the cancer subtype. In the multivariate analysis, only lymph node (LN) metastasis was an independent prognostic factor for recurrent/persistent disease of thyroid cancer arising in GD (P=0.020).
Conclusion
The prevalence of concomitant thyroid cancer in GD patients was considerably lower than in previous reports. The clinical outcomes of thyroid cancer in GD patients were also excellent but, more cautious follow-up is necessary for patients with LN metastasis in the same way as for thyroid cancer in non-GD patients.

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  • Outcomes of Surgical Treatment for Graves’ Disease: A Single-Center Experience of 216 Cases
    Hanxing Sun, Hui Tong, Xiaohui Shen, Haoji Gao, Jie Kuang, Xi Chen, Qinyu Li, Weihua Qiu, Zhuoran Liu, Jiqi Yan
    Journal of Clinical Medicine.2023; 12(4): 1308.     CrossRef
  • Table of Contents

    Clinical Thyroidology.2022; 34(2): 48.     CrossRef
  • Predisposition to and Prognosis of Thyroid Cancer May Not Be Affected by Graves’ Disease, But Some Questions Still Remain
    Yanrui Huang, Haixia Guan
    Clinical Thyroidology.2022; 34(2): 59.     CrossRef
  • A Comparative Follow-Up Study of Patients with Papillary Thyroid Carcinoma Associated or Not with Graves’ Disease
    Andrea Marongiu, Susanna Nuvoli, Andrea De Vito, Maria Rondini, Angela Spanu, Giuseppe Madeddu
    Diagnostics.2022; 12(11): 2801.     CrossRef
Thyroid
Clinicopathological Characteristics and Disease-Free Survival in Patients with Hürthle Cell Carcinoma: A Multicenter Cohort Study in South Korea
Meihua Jin, Eun Sook Kim, Bo Hyun Kim, Hee Kyung Kim, Yea Eun Kang, Min Ji Jeon, Tae Yong Kim, Ho-Cheol Kang, Won Bae Kim, Young Kee Shong, Mijin Kim, Won Gu Kim
Endocrinol Metab. 2021;36(5):1078-1085.   Published online October 28, 2021
DOI: https://doi.org/10.3803/EnM.2021.1151
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   CrossRef-TDMCrossref - TDM
Background
Hürthle cell carcinoma (HCC), a type of thyroid carcinoma, is rare in South Korea, and few studies have investigated its prognosis.
Methods
This long-term multicenter retrospective cohort study evaluated the clinicopathological features and clinical outcomes in patients with HCC who underwent thyroid surgery between 1996 and 2009.
Results
The mean age of the 97 patients included in the study was 50.3 years, and 26.8% were male. The mean size of the primary tumor was 3.2±1.8 cm, and three (3.1%) patients had distant metastasis at initial diagnosis. Ultrasonographic findings were available for 73 patients; the number of nodules with low-, intermediate-, and high suspicion was 28 (38.4%), 27 (37.0%), and 18 (24.7%), respectively, based on the Korean-Thyroid Imaging Reporting and Data System. Preoperatively, follicular neoplasm (FN) or suspicion for FN accounted for 65.2% of the cases according to the Bethesda category, and 13% had malignancy or suspicious for malignancy. During a median follow-up of 8.5 years, eight (8.2%) patients had persistent/recurrent disease, and none died of HCC. Older age, gross extrathyroidal extension (ETE), and widely invasive types of tumors were significantly associated with distant metastasis (all P<0.01). Gross ETE (hazard ratio [HR], 27.7; 95% confidence interval [CI], 2.2 to 346.4; P=0.01) and widely invasive classification (HR, 6.5; 95% CI, 1.1 to 39.4; P=0.04) were independent risk factors for poor disease-free survival (DFS).
Conclusion
The long-term prognosis of HCC is relatively favorable in South Korea from this study, although this is not a nation-wide data, and gross ETE and widely invasive cancer are significant prognostic factors for DFS. The diagnosis of HCC by ultrasonography and cytopathology remains challenging.

Citations

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  • Hürthle Cell Carcinoma: Single Center Analysis and Considerations for Surgical Management Based on the Recent Literature
    Costanza Chiapponi, Milan J.M. Hartmann, Matthias Schmidt, Michael Faust, Christiane J. Bruns, Anne M. Schultheis, Hakan Alakus
    Frontiers in Endocrinology.2022;[Epub]     CrossRef
Thyroid
Active Surveillance as an Effective Management Option for Low-Risk Papillary Thyroid Microcarcinoma
Min Ji Jeon, Won Gu Kim, Tae Yong Kim, Young Kee Shong, Won Bae Kim
Endocrinol Metab. 2021;36(4):717-724.   Published online August 11, 2021
DOI: https://doi.org/10.3803/EnM.2021.1042
Correction in: Endocrinol Metab 2022;37(1):180
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AbstractAbstract PDFPubReader   ePub   CrossRef-TDMCrossref - TDM
Active surveillance (AS) for low-risk papillary thyroid microcarcinoma (PTMC) has been accepted worldwide as safe and effective. Despite the growing acceptance of AS in the management of low-risk PTMCs, there are barriers to AS in real clinical settings, and it is important to understand and establish appropriate AS protocol from initial evaluation to follow-up. PTMC management strategies should be decided upon after careful consideration of patient and tumor characteristics by a multidisciplinary team of thyroid cancer specialists. Patients should understand the risks and benefits of AS, participate in decision-making and follow structured monitoring strategies. In this review, we discuss clinical outcomes of AS from previous studies, optimal indications and follow-up strategies for AS, and unresolved questions about AS.

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  • Serum thyroglobulin testing after thyroid lobectomy in patients with 1–4 cm papillary thyroid carcinoma
    Ahreum Jang, Meihua Jin, Chae A Kim, Min Ji Jeon, Yu-Mi Lee, Tae-Yon Sung, Tae Yong Kim, Won Bae Kim, Young Kee Shong, Won Gu Kim
    Endocrine.2023;[Epub]     CrossRef
  • Papillary Thyroid Microcarcinoma: Active Surveillance Against Surgery. Considerations of an Italian Working Group From a Systematic Review
    Giuseppina Orlando, Gregorio Scerrino, Alessandro Corigliano, Irene Vitale, Roberta Tutino, Stefano Radellini, Francesco Cupido, Giuseppa Graceffa, Gianfranco Cocorullo, Giuseppe Salamone, Giuseppina Melfa
    Frontiers in Oncology.2022;[Epub]     CrossRef
  • Prognosis of Patients with 1–4 cm Papillary Thyroid Cancer Who Underwent Lobectomy: Focus on Gross Extrathyroidal Extension Invading Only the Strap Muscles
    Ahreum Jang, Meihua Jin, Won Woong Kim, Min Ji Jeon, Tae-Yon Sung, Dong Eun Song, Tae Yong Kim, Ki-Wook Chung, Won Bae Kim, Young Kee Shong, Yu-Mi Lee, Won Gu Kim
    Annals of Surgical Oncology.2022; 29(12): 7835.     CrossRef
Clinical Study
Protocol for a Korean Multicenter Prospective Cohort Study of Active Surveillance or Surgery (KoMPASS) in Papillary Thyroid Microcarcinoma
Min Ji Jeon, Yea Eun Kang, Jae Hoon Moon, Dong Jun Lim, Chang Yoon Lee, Yong Sang Lee, Sun Wook Kim, Min-Hee Kim, Bo Hyun Kim, Ho-Cheol Kang, Minho Shong, Sun Wook Cho, Won Bae Kim
Endocrinol Metab. 2021;36(2):359-364.   Published online March 23, 2021
DOI: https://doi.org/10.3803/EnM.2020.890
Correction in: Endocrinol Metab 2022;37(1):181
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AbstractAbstract PDFPubReader   ePub   CrossRef-TDMCrossref - TDM
Background
A Korean Multicenter Prospective cohort study of Active Surveillance or Surgery (KoMPASS) for papillary thyroid microcarcinomas (PTMCs) has been initiated. The aim is to compare clinical outcomes between active surveillance (AS) and an immediate lobectomy for low-risk PTMCs. We here outline the detailed protocol for this study.
Methods
Adult patients with a cytopathologically confirmed PTMC sized 6.0 to 10.0 mm by ultrasound (US) will be included. Patients will be excluded if they have a suspicious extra-thyroidal extension or metastasis of a PTMC or multiple thyroid nodules or other thyroid diseases which require a total thyroidectomy. Printed material describing the prognosis of PTMCs, and the pros and cons of each management option, will be provided to eligible patients to select their preferred intervention. For the AS group, thyroid US, thyroid function, and quality of life (QoL) parameters will be monitored every 6 months during the first year, and then annually thereafter. Disease progression will be defined as a ≥3 mm increase in maximal diameter of a PTMC, or the development of new thyroid cancers or metastases. If progression is detected, patients should undergo appropriate surgery. For the lobectomy group, a lobectomy with prophylactic central neck dissection will be done within 6 months. After initial surgery, thyroid US, thyroid function, serum thyroglobulin (Tg), anti-Tg antibody, and QoL parameters will be monitored every 6 months during the first year and annually thereafter. Disease progression will be defined in these cases as the development of new thyroid cancers or metastases.
Conclusion
KoMPASS findings will help to confirm the role of AS, and develop individualized management strategies, for low-risk PTMCs.

Citations

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  • Thyroid-Stimulating Hormone, Age, and Tumor Size are Risk Factors for Progression During Active Surveillance of Low-Risk Papillary Thyroid Microcarcinoma in Adults
    Yasuhiro Ito, Akira Miyauchi, Makoto Fujishima, Takuya Noda, Tsutomu Sano, Takahiro Sasaki, Taketoshi Kishi, Tomohiko Nakamura
    World Journal of Surgery.2023; 47(2): 392.     CrossRef
  • Thyroid FNA cytology: The Eastern versus Western perspectives
    Mitsuyoshi Hirokawa, Manon Auger, Chan Kwon Jung, Fabiano Mesquita Callegari
    Cancer Cytopathology.2023;[Epub]     CrossRef
  • Thermal ablation for papillary thyroid microcarcinoma located in the isthmus: a study with 3 years of follow-up
    Lin Zheng, Fang-yi Liu, Jie Yu, Zhi-gang Cheng, Xiao-ling Yu, Xiao-cong Dong, Zhi-yu Han, Ping Liang
    Future Oncology.2022; 18(4): 471.     CrossRef
  • Trends in the Management of Localized Papillary Thyroid Carcinoma in the United States (2000–2018)
    Elisa Pasqual, Julie Ann Sosa, Yingxi Chen, Sara J. Schonfeld, Amy Berrington de González, Cari M. Kitahara
    Thyroid.2022; 32(4): 397.     CrossRef
  • Management of Low-Risk Thyroid Cancers: Is Active Surveillance a Valid Option? A Systematic Review of the Literature
    Renato Patrone, Nunzio Velotti, Stefania Masone, Alessandra Conzo, Luigi Flagiello, Chiara Cacciatore, Marco Filardo, Vincenza Granata, Francesco Izzo, Domenico Testa, Stefano Avenia, Alessandro Sanguinetti, Andrea Polistena, Giovanni Conzo
    Journal of Clinical Medicine.2021; 10(16): 3569.     CrossRef
  • Cost-Effectiveness Analysis of Active Surveillance Compared to Early Surgery in Small Papillary Thyroid Cancer: A Systemic Review
    Han-sang Baek, Chai-ho Jeong, Jeonghoon Ha, Ja-Seong Bae, Jeong-soo Kim, Dong-Jun Lim, Chul-Min Kim
    Cancer Management and Research.2021; Volume 13: 6721.     CrossRef
  • Active Surveillance as an Effective Management Option for Low-Risk Papillary Thyroid Microcarcinoma
    Min Ji Jeon, Won Gu Kim, Tae Yong Kim, Young Kee Shong, Won Bae Kim
    Endocrinology and Metabolism.2021; 36(4): 717.     CrossRef
Clinical Study
Gender-Dependent Reference Range of Serum Calcitonin Levels in Healthy Korean Adults
Eyun Song, Min Ji Jeon, Hye Jin Yoo, Sung Jin Bae, Tae Yong Kim, Won Bae Kim, Young Kee Shong, Hong-Kyu Kim, Won Gu Kim
Endocrinol Metab. 2021;36(2):365-373.   Published online April 7, 2021
DOI: https://doi.org/10.3803/EnM.2020.939
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   CrossRef-TDMCrossref - TDM
Background
Serum calcitonin measurement contains various clinical and methodological aspects. Its reference level is wide and unclear despite sensitive calcitonin kits are available. This study aimed to identify the specific reference range in the healthy Korean adults.
Methods
Subjects were ≥20 years with available calcitonin (measured by a two-site immunoradiometric assay) data by a routine health checkup. Three groups were defined as all eligible subjects (group 1, n=10,566); subjects without self or family history of thyroid disease (group 2, n=5,152); and subjects without chronic kidney disease, autoimmune thyroid disease, medication of proton pump inhibitor/H2 blocker/steroid, or other malignancies (group 3, n=4,638).
Results
This study included 6,341 male and 4,225 female subjects. Males had higher mean calcitonin than females (2.3 pg/mL vs. 1.9 pg/mL, P<0.001) in group 1. This gender difference remained similar in groups 2 and 3. Calcitonin according to age or body mass index was not significant in both genders. Higher calcitonin in smoking than nonsmoking men was observed but not in women. Sixty-nine subjects had calcitonin higher than the upper reference limit (10 pg/mL) and 64 of them had factors associated with hypercalcitoninemia besides medullary thyroid cancer. Our study suggests the reference intervals for men who were non, ex-, current smokers, and women (irrespective of smoking status) as <5.7, <7.1, <7.9, and <3.6 pg/mL, respectively.
Conclusion
Specific calcitonin reference range should be provided considering for sex and smoking status. Taking account for several factors known to induce hypercalcitoninemia can help interpret the gray zone of moderately elevated calcitonin.

Citations

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  • Presence or severity of Hashimoto’s thyroiditis does not influence basal calcitonin levels: observations from CROHT biobank
    M. Cvek, A. Punda, M. Brekalo, M. Plosnić, A. Barić, D. Kaličanin, L. Brčić, M. Vuletić, I. Gunjača, V. Torlak Lovrić, V. Škrabić, V. Boraska Perica
    Journal of Endocrinological Investigation.2022; 45(3): 597.     CrossRef
  • Environmental Factors That Affect Parathyroid Hormone and Calcitonin Levels
    Mirjana Babić Leko, Nikolina Pleić, Ivana Gunjača, Tatijana Zemunik
    International Journal of Molecular Sciences.2021; 23(1): 44.     CrossRef
Clinical Study
Clinical Outcomes after Early and Delayed Radioiodine Remnant Ablation in Patients with Low-Risk Papillary Thyroid Carcinoma: Propensity Score Matching Analysis
Jonghwa Ahn, Meihua Jin, Eyun Song, Min Ji Jeon, Tae Yong Kim, Jin-Sook Ryu, Won Bae Kim, Young Kee Shong, Ji Min Han, Won Gu Kim
Endocrinol Metab. 2020;35(4):830-837.   Published online November 18, 2020
DOI: https://doi.org/10.3803/EnM.2020.747
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   CrossRef-TDMCrossref - TDM
Background
The clinical outcomes of delayed radioiodine remnant ablation (RRA) therapy in patients with low-risk papillary thyroid carcinoma (PTC) are unclear. We aimed to evaluate the clinical impact of the interval between total thyroidectomy (TT) and RRA therapy in patients with low-risk PTC.
Methods
We included 526 patients who underwent TT and RRA for low-risk PTC with a primary tumor size of >1 cm between 2000 and 2012. Patients were divided into the early (<90 days) and the delayed (≥90 days) RRA groups based on the interval between TT and RRA. The results of diagnostic whole-body scan (DxWBS), ongoing risk stratification (ORS; response to therapy), and disease-free survival (DFS) were evaluated before and after propensity score matching (PSM).
Results
Among the 526 patients, 75 (14.3%) patients underwent delayed RRA; they had more cervical lymph node metastasis and received a higher RRA dose than those who underwent early RRA. The median follow-up period was 9.1 years after initial therapy, and the structural recurrence rate was 1.9%. In DxWBS, 60 patients had focal iodine uptake limited in operative bed, with no significant difference between groups. According to ORS, 78%, 20%, 1%, and 1% patients were classified into excellent, indeterminate, biochemical incomplete, and structural incomplete response groups, respectively. There was no significant difference in ORS or DFS between groups before and after PSM.
Conclusion
The timing of the first RRA had no clinical impact in patients with low-risk PTC. Thus, the clinical decision for RRA can be determined >3 months after TT considering other prognostic factors.

Citations

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  • Patient Preparation and Radiation Protection Guidance for Adult Patients Undergoing Radioiodine Treatment for Thyroid Cancer in the UK
    J. Wadsley, N. Armstrong, V. Bassett-Smith, M. Beasley, R. Chandler, L. Cluny, A.J. Craig, K. Farnell, K. Garcez, N. Garnham, K. Graham, A. Hallam, S. Hill, H. Hobrough, F. McKiddie, M.W.J. Strachan
    Clinical Oncology.2023; 35(1): 42.     CrossRef
  • Delay of initial radioactive iodine therapy beyond 3 months has no effect on clinical responses and overall survival in patients with thyroid carcinoma: A cohort study and a meta‐analysis
    Fang Cheng, Juan Xiao, Fengyan Huang, Chunchun Shao, Shouluan Ding, Canhua Yun, Hongying Jia
    Cancer Medicine.2022; 11(12): 2386.     CrossRef
  • Delayed (>3 Months) Postoperative Radioactive Iodine Ablation Does Not Impact Clinical Response or Survival in Differentiated Thyroid Cancers
    Tatiana Fedorova, Lilah F. Morris-Wiseman
    Clinical Thyroidology.2022; 34(10): 456.     CrossRef
Clinical Study
Clinical Outcomes of N1b Papillary Thyroid Cancer Patients Treated with Two Different Doses of Radioiodine Ablation Therapy
Meihua Jin, Jonghwa Ahn, Yu-Mi Lee, Tae-Yon Sung, Won Gu Kim, Tae Yong Kim, Jin-Sook Ryu, Won Bae Kim, Young Kee Shong, Min Ji Jeon
Endocrinol Metab. 2020;35(3):602-609.   Published online September 22, 2020
DOI: https://doi.org/10.3803/EnM.2020.741
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AbstractAbstract PDFPubReader   ePub   CrossRef-TDMCrossref - TDM
Background
The optimal dose of radioactive iodine (RAI) therapy for N1b papillary thyroid carcinoma (PTC) is controversial. We evaluated the clinical outcome of N1b PTC patients treated with either 100 or 150 mCi of RAI.
Methods
We retrospectively analyzed N1b PTC patients who underwent total thyroidectomy and postoperative RAI therapy at a tertiary referral center between 2012 and 2017. As the baseline characteristics differed between treatment groups, we performed exact matching for various pathological factors according to RAI dose. We evaluated the response to therapy and recurrence-free survival (RFS) in the matched patients. Structural recurrent/persistent disease was defined as new structural disease detected after initial therapy, which was confirmed by cytology or pathology.
Results
Of the total 436 patients, 37 (8.5%) received 100 mCi of RAI and 399 (91.5%) received 150 mCi of RAI. After an exact 1:3 matching, 34 patients in the 100 mCi group and 100 patients in the 150 mCi group remained. There was no significant difference in response to therapy between the groups in the matched population (P=0.63). An excellent response was achieved in 70.6% (n=24) of patients in the 100 mCi group and 76.0% (n=76) in the 150 mCi group. Two (5.9%) patients in the 100 mCi group and four (4.0%) in the 150 mCi group had recurrence and there was no significant difference in RFS between the groups in the matched population (P=0.351).
Conclusion
There were no differences in response to therapy and RFS in N1b PTC patients according to RAI dose.
Clinical Study
Clinical Implication of World Health Organization Classification in Patients with Follicular Thyroid Carcinoma in South Korea: A Multicenter Cohort Study
Meihua Jin, Eun Sook Kim, Bo Hyun Kim, Hee Kyung Kim, Hyon-Seung Yi, Min Ji Jeon, Tae Yong Kim, Ho-Cheol Kang, Won Bae Kim, Young Kee Shong, Mijin Kim, Won Gu Kim
Endocrinol Metab. 2020;35(3):618-627.   Published online September 22, 2020
DOI: https://doi.org/10.3803/EnM.2020.742
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AbstractAbstract PDFPubReader   ePub   CrossRef-TDMCrossref - TDM
Background
The study aimed to compare the prognostic value of the 4th edition of World Health Organization classification (WHO-2017) with the previous WHO classification (WHO-2004) for follicular thyroid carcinoma (FTC).
Methods
This multicenter retrospective cohort study included 318 patients with FTC from five tertiary centers who underwent thyroid surgery between 1996 and 2009. We evaluated the prognosis of patients with minimally invasive (MI), encapsulated angioinvasive (EA), and widely invasive (WI) FTC according to WHO-2017. Further, we evaluated the proportion of variation explained (PVE) and Harrell’s C-index to compare the predictability of disease-free survival (DFS) and disease-specific survival (DSS).
Results
In total, 227, 58, and 33 patients had MI-, EA-, and WI-FTC, respectively. During a median follow-up of 10.6 years, 46 (14.5%) patients had disease recurrence and 20 (6.3%) patients died from FTC. The 10-year DFS rates of patients with MI-, EA-, and WI-FTC were 91.1%, 78.2%, and 54.9%, respectively (P<0.001, PVE=7.1%, C-index=0.649). The corresponding 10-year DSS rates were 95.9%, 93.5%, and 73.5%, respectively (P<0.001, PVE=2.6%, C-index=0.624). The PVE and C-index values were higher using WHO-2017 than using WHO-2004 for the prediction of DFS, but not for DSS. In multivariate analysis, older age (P=0.02), gross extrathyroidal extension (ETE) (P=0.003), and distant metastasis (P<0.001) were independent risk factors for DSS.
Conclusion
WHO-2017 improves the predictability of DFS, but not DSS, in patients with FTC. Distant metastasis, gross ETE and older age (≥55 years) were independent risk factors for DSS.

Citations

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  • The Prognostic Impact of Extent of Vascular Invasion in Follicular Thyroid Carcinoma
    David Leong, Anthony J. Gill, John Turchini, Michael Waller, Roderick Clifton-Bligh, Anthony Glover, Mark Sywak, Stan Sidhu
    World Journal of Surgery.2023; 47(2): 412.     CrossRef
  • Molecular classification of follicular thyroid carcinoma based on TERT promoter mutations
    Hyunju Park, Hyeong Chan Shin, Heera Yang, Jung Heo, Chang-Seok Ki, Hye Seung Kim, Jung-Han Kim, Soo Yeon Hahn, Yun Jae Chung, Sun Wook Kim, Jae Hoon Chung, Young Lyun Oh, Tae Hyuk Kim
    Modern Pathology.2022; 35(2): 186.     CrossRef
  • Whole-genome Sequencing of Follicular Thyroid Carcinomas Reveal Recurrent Mutations in MicroRNA Processing Subunit DGCR8
    Johan O Paulsson, Nima Rafati, Sebastian DiLorenzo, Yi Chen, Felix Haglund, Jan Zedenius, C Christofer Juhlin
    The Journal of Clinical Endocrinology & Metabolism.2021; 106(11): 3265.     CrossRef
  • Clinicopathological Characteristics and Disease-Free Survival in Patients with Hürthle Cell Carcinoma: A Multicenter Cohort Study in South Korea
    Meihua Jin, Eun Sook Kim, Bo Hyun Kim, Hee Kyung Kim, Yea Eun Kang, Min Ji Jeon, Tae Yong Kim, Ho-Cheol Kang, Won Bae Kim, Young Kee Shong, Mijin Kim, Won Gu Kim
    Endocrinology and Metabolism.2021; 36(5): 1078.     CrossRef
Clinical Study
Quality of Life in Patients with Papillary Thyroid Microcarcinoma According to Treatment: Total Thyroidectomy with or without Radioactive Iodine Ablation
Jonghwa Ahn, Min Ji Jeon, Eyun Song, Tae Yong Kim, Won Bae Kim, Young Kee Shong, Won Gu Kim
Endocrinol Metab. 2020;35(1):115-121.   Published online March 19, 2020
DOI: https://doi.org/10.3803/EnM.2020.35.1.115
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AbstractAbstract PDFPubReader   ePub   CrossRef-TDMCrossref - TDM
Background

Recently, there has been some controversy regarding the role of radioactive iodine (RAI) ablation in the treatment of low-risk differentiated thyroid carcinoma (DTC), especially papillary thyroid microcarcinoma (PTMC). This study aimed to compare quality of life (QoL) parameters between patients with PTMC who underwent total thyroidectomy (TT) alone and those who underwent TT with RAI ablation.

Methods

In this cross-sectional study, patients with PTMC who underwent TT with/without RAI remnant ablation were prospectively enrolled between June 2016 and October 2017. All patients completed three questionnaires: the 12-item short-form health survey (SF-12), thyroid cancer-specific quality of life (THYCA-QoL) questionnaire, and fear of progression (FoP) questionnaire.

Results

The TT and TT with RAI groups comprised 107 and 182 patients, respectively. The TT with RAI group had significantly lower serum thyrotropin (TSH) levels than the TT group. However, after matching for TSH levels between the groups (n=100 in both groups), there were no significant differences in baseline characteristics. According to the SF-12, the score for general health was significantly lower in the TT with RAI group than in the TT group (P=0.047). The THYCA-QoL also showed a significant difference in the “felt chilly” score between groups (P=0.023). No significant differences in FoP scores were observed between the groups.

Conclusion

Patients with PTMC who underwent TT with RAI ablation experienced more health-related problems than those managed with TT alone. These findings support the idea that RAI ablation should be carefully considered in patients with low-risk DTCs.

Citations

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  • Review: Improving quality of life in patients with differentiated thyroid cancer
    Pia Pace-Asciak, Jonathon O. Russell, Ralph P. Tufano
    Frontiers in Oncology.2023;[Epub]     CrossRef
  • Health-Related Quality of Life and Thyroid Cancer-Specific Symptoms in Patients Treated for Differentiated Thyroid Cancer: A Single-Center Cross-Sectional Survey from Mainland China
    Changlian Chen, Jiayan Cao, Yueyang Wang, Xuya Han, Yaju Zhang, Shumei Zhuang
    Thyroid.2023;[Epub]     CrossRef
  • Risk of Adverse Pregnancy Outcomes in Young Women with Thyroid Cancer: A Systematic Review and Meta-Analysis
    Shinje Moon, Ka Hee Yi, Young Joo Park
    Cancers.2022; 14(10): 2382.     CrossRef
  • Health-related quality of life following FDG-PET/CT for cytological indeterminate thyroid nodules
    Elizabeth J de Koster, Olga Husson, Eveline W C M van Dam, G Sophie Mijnhout, Romana T Netea-Maier, Wim J G Oyen, Marieke Snel, Lioe-Fee de Geus-Oei, Dennis Vriens, _ _
    Endocrine Connections.2022;[Epub]     CrossRef
  • Is a four-week hormone suspension necessary for thyroid remnant ablation in low and intermediate risk patients? A pilot study with quality-of-life assessment
    Poliane A.L. Santos, Maria E.D.M. Flamini, Felipe A. Mourato, Fernando R.A. Lima, Joelan A.L. Santos, Fabiana F. Lima, Estelita T.B. Albuquerque, Alexandra C. De Freitas, Simone C.S. Brandão
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    Chang Myeon Song, Hyang Sook Bang, Hyung Gu Kim, Hae Jin Park, Kyung Tae
    Surgery.2021; 170(1): 99.     CrossRef
  • Protocol for a Korean Multicenter Prospective Cohort Study of Active Surveillance or Surgery (KoMPASS) in Papillary Thyroid Microcarcinoma
    Min Ji Jeon, Yea Eun Kang, Jae Hoon Moon, Dong Jun Lim, Chang Yoon Lee, Yong Sang Lee, Sun Wook Kim, Min-Hee Kim, Bo Hyun Kim, Ho-Cheol Kang, Minho Shong, Sun Wook Cho, Won Bae Kim
    Endocrinology and Metabolism.2021; 36(2): 359.     CrossRef
Thyroid
Unmet Clinical Needs in the Treatment of Patients with Thyroid Cancer
Won Bae Kim, Min Ji Jeon, Won Gu Kim, Tae Yong Kim, Young Kee Shong
Endocrinol Metab. 2020;35(1):14-25.   Published online March 19, 2020
DOI: https://doi.org/10.3803/EnM.2020.35.1.14
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AbstractAbstract PDFPubReader   ePub   CrossRef-TDMCrossref - TDM

The increased incidence of thyroid cancer is a worldwide phenomenon; however, the issue of overdiagnosis has been most prominent in South Korea. The age-standardized mortality rate of thyroid cancer in Korea steeply increased from 1985 to 2004 (from 0.17 per 100,000 to 0.85 per 100,000), and then decreased until 2015 to 0.42 per 100,000, suggesting that early detection reduced mortality. However, early detection of thyroid cancer may be cost-ineffective, considering its very high prevalence and indolent course. Therefore, risk stratification and tailored management are vitally important, but many prognostic markers can only be evaluated postoperatively. Discovery of preoperative marker(s), especially for small cancers, is the most important unmet clinical need for thyroid cancer. Herein, we discuss some such factors that we recently discovered. Another unmet clinical need is better treatment of radioiodine-refractory (RAIR) differentiated thyroid cancer (DTC) and undifferentiated cancers. Although sorafenib and lenvatinib are available, better drugs are needed. We found that phosphoglycerate dehydrogenase, a critical enzyme for serine biosynthesis, could be a novel therapeutic target, and that the lymphocyte-to-monocyte ratio is a prognostic marker of survival in patients with anaplastic thyroid carcinoma or RAIR DTC. Deeper insights are needed into tumor-host interactions in thyroid cancer to improve treatment.

Citations

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  • Lenvatinib Compared with Sorafenib as a First-Line Treatment for Radioactive Iodine-Refractory, Progressive, Differentiated Thyroid Carcinoma: Real-World Outcomes in a Multicenter Retrospective Cohort Study
    Mijin Kim, Meihua Jin, Min Ji Jeon, Eui Young Kim, Dong Yeob Shin, Dong Jun Lim, Bo Hyun Kim, Ho-Cheol Kang, Won Bae Kim, Young Kee Shong, Hee Kyung Kim, Won Gu Kim
    Thyroid.2023; 33(1): 91.     CrossRef
  • Transcriptomic Analysis of Papillary Thyroid Cancer: A Focus on Immune-Subtyping, Oncogenic Fusion, and Recurrence
    Seung-Jin Park, Yea Eun Kang, Jeong-Hwan Kim, Jong-Lyul Park, Seon-Kyu Kim, Seung-Woo Baek, In Sun Chu, Shinae Yi, Seong Eun Lee, Young Joo Park, Eun-Jae Chung, Jin Man Kim, Hye Mi Ko, Je-Ryong Kim, Seung-Nam Jung, Ho-Ryun Won, Jae Won Chang, Bon Seok Koo
    Clinical and Experimental Otorhinolaryngology.2022; 15(2): 183.     CrossRef
  • Prognosis of Patients with 1–4 cm Papillary Thyroid Cancer Who Underwent Lobectomy: Focus on Gross Extrathyroidal Extension Invading Only the Strap Muscles
    Ahreum Jang, Meihua Jin, Won Woong Kim, Min Ji Jeon, Tae-Yon Sung, Dong Eun Song, Tae Yong Kim, Ki-Wook Chung, Won Bae Kim, Young Kee Shong, Yu-Mi Lee, Won Gu Kim
    Annals of Surgical Oncology.2022; 29(12): 7835.     CrossRef
  • Carboxy terminus of HSP70 ‐interacting protein ( CHIP ) attenuates the stemness of thyroid cancer cells through decreasing OCT4 protein stability
    Ying Xu, Gang Xu, Huimin Dang, Wei Qu, Dan Chang, Xin He, Minmin Li, Qian Wang
    Environmental Toxicology.2021; 36(4): 686.     CrossRef
  • Lactate Dehydrogenase A as a Potential New Biomarker for Thyroid Cancer
    Eun Jeong Ban, Daham Kim, Jin Kyong Kim, Sang-Wook Kang, Jandee Lee, Jong Ju Jeong, Kee-Hyun Nam, Woong Youn Chung, Kunhong Kim
    Endocrinology and Metabolism.2021; 36(1): 96.     CrossRef
  • Clinical implications of age and excellent response to therapy in patients with high‐risk differentiated thyroid carcinoma
    Meihua Jin, Jonghwa Ahn, Yu‐Mi Lee, Tae‐Yon Sung, Dong Eun Song, Tae Yong Kim, Ki‐Wook Chung, Jin‐Sook Ryu, Won Bae Kim, Young Kee Shong, Min Ji Jeon, Won Gu Kim
    Clinical Endocrinology.2021; 95(6): 882.     CrossRef
  • CD73 Overexpression Promotes Progression and Recurrence of Papillary Thyroid Carcinoma
    Young Mun Jeong, Haejin Cho, Tae-Min Kim, Yourha Kim, Sora Jeon, Andrey Bychkov, Chan Kwon Jung
    Cancers.2020; 12(10): 3042.     CrossRef
  • The Role of Exosomes in Thyroid Cancer and Their Potential Clinical Application
    Kaixiang Feng, Runsheng Ma, Lele Zhang, Hongqiang Li, Yifeng Tang, Gongbo Du, Dongpeng Niu, Detao Yin
    Frontiers in Oncology.2020;[Epub]     CrossRef
Clinical Study
Modification of the Tumor-Node-Metastasis Staging System for Differentiated Thyroid Carcinoma by Considering Extra-Thyroidal Extension and Lateral Cervical Lymph Node Metastasis
Mijin Kim, Won Gu Kim, Min Ji Jeon, Hee Kyung Kim, Hyon-Seung Yi, Eun Sook Kim, Bo Hyun Kim, Won Bae Kim, Young Kee Shong, Ho-Cheol Kang, Tae Yong Kim
Endocrinol Metab. 2020;35(1):149-156.   Published online March 19, 2020
DOI: https://doi.org/10.3803/EnM.2020.35.1.149
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AbstractAbstract PDFPubReader   ePub   CrossRef-TDMCrossref - TDM
Background

Concerns have arisen about the classification of extra-thyroidal extension (ETE) and lateral cervical lymph node metastasis (N1b) in the 8th edition of the tumor-node-metastasis staging system (TNM-8). This study evaluated the prognostic validity of a modified-TNM staging system, focusing on ETE and N1b, in differentiated thyroid carcinoma (DTC) patients.

Methods

This multicenter retrospective cohort study included 4,878 DTC patients from five tertiary hospitals. In the modified-TNM, T3b in TNM-8 was down-staged to T2, and stage II was subdivided into stages IIA and IIB. Older patients with N1b were reclassified as stage IIB.

Results

The modified-TNM resulted in staging migration in 540 patients (11%) classified as stage II according to the TNM-8, with 75 (14%), 381 (71%), and 84 patients (16%) classified as stages I, IIA, and IIB, respectively. The 10-year disease-specific survival (DSS) rates in patients classified as stages I, II, III, and IV by TNM-8 were 99.8%, 95.9%, 81.0%, and 41.6%, respectively. The DSS rates of patients classified as stages I, IIA, IIB, III, and IV according to the modified-TNM were 99.8%, 96.4%, 93.3%, 81.0%, and 41.6%, respectively. DSS curves between stages on TNM-8 (P<0.001) and modified-TNM (P<0.001) differed significantly, but the modified-TNM discriminated better than TNM-8. The proportions of variation explained values of TNM-8 and modified-TNM were 6.3% and 6.5%, respectively.

Conclusion

Modification of the TNM staging system focusing on ETE and N1b could improve the prediction of DSS in patients with DTC. Further researches are needed to validate the prognostic accuracy of this modified-TNM staging system.

Citations

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  • Thyroid Collision Tumors: The Presence of the Medullary Thyroid Carcinoma Component Negatively Influences the Prognosis
    Ion Negura, Victor Ianole, Mihai Danciu, Cristina Preda, Diana Gabriela Iosep, Radu Dănilă, Alexandru Grigorovici, Delia Gabriela Ciobanu Apostol
    Diagnostics.2023; 13(2): 285.     CrossRef
  • Serum thyroglobulin testing after thyroid lobectomy in patients with 1–4 cm papillary thyroid carcinoma
    Ahreum Jang, Meihua Jin, Chae A Kim, Min Ji Jeon, Yu-Mi Lee, Tae-Yon Sung, Tae Yong Kim, Won Bae Kim, Young Kee Shong, Won Gu Kim
    Endocrine.2023;[Epub]     CrossRef
  • Prognostic Impact of Microscopic Extra-Thyroidal Extension (mETE) on Disease Free Survival in Patients with Papillary Thyroid Carcinoma (PTC)
    Nadia Bouzehouane, Pascal Roy, Myriam Decaussin-Petrucci, Mireille Bertholon-Grégoire, Chantal Bully, Agnès Perrin, Helene Lasolle, Jean-Christophe Lifante, Françoise Borson-Chazot, Claire Bournaud
    Cancers.2022; 14(11): 2591.     CrossRef
  • Impacts of the American Joint Committee on Cancer (AJCC) 8th edition tumor, node, metastasis (TNM) staging system on outcomes of differentiated thyroid cancer in Thai patients
    Yotsapon Thewjitcharoen, Waralee Chatchomchuan, Krittadhee Karndumri, Sriurai Porramatikul, Sirinate Krittiyawong, Ekgaluck Wanothayaroj, Siriwan Butadej, Soontaree Nakasatien, Veekij Veerasomboonsin, Auchai Kanchanapituk, Rajata Rajatanavin, Thep Himatho
    Heliyon.2021; 7(3): e06624.     CrossRef
Endocrine Research
Expression of NF2 Modulates the Progression of BRAFV600E Mutated Thyroid Cancer Cells
Mi-Hyeon You, Min Ji Jeon, Tae Yong Kim, Won Bae Kim, Young Kee Shong, Won Gu Kim
Endocrinol Metab. 2019;34(2):203-212.   Published online June 24, 2019
DOI: https://doi.org/10.3803/EnM.2019.34.2.203
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   CrossRef-TDMCrossref - TDM
Background

We previously reported the frequent neurofibromatosis 2 (NF2) gene mutations in anaplastic thyroid cancers in association with the BRAFV600E mutation. We aimed to investigate the role of NF2 in thyroid cancer with BRAF mutation.

Methods

To identify the function of NF2 in thyroid cancers, we investigated the changes in cell proliferation, colon formation, migration and invasion of thyroid cancer cells (8505C, BHT101, and KTC-1) with BRAFV600E mutation after overexpression and knock-down of NF2. We also examined how cell proliferation changed when NF2 was mutagenized. Human NF2 expression in papillary thyroid carcinoma (PTC) was analyzed using the The Cancer Genome Atlas (TCGA) data.

Results

First, NF2 was overexpressed in 8505C and KTC-1 cells. Compared to control, NF2 overexpressed group of both thyroid cancer cells showed significant inhibition in cell proliferation and colony formation. These results were also confirmed by cell migration and invasion assay. After knock-down of NF2 in 8505C cells, there were no significant changes in cell proliferation and colony formation, compared with the control group. However, after mutagenized S288* and Q470* sites of NF2 gene, the cell proliferation increased compared to NF2 overexpression group. In the analysis of TCGA data, the mRNA expression of NF2 was significantly decreased in PTCs with lateral cervical lymph node (LN) metastasis compared with PTCs without LN metastasis.

Conclusion

Our study suggests that NF2 might play a role as a tumor suppressor in thyroid cancer with BRAF mutation. More studies are needed to elucidate the mechanism how NF2 acts in thyroid cancer with BRAF mutation.

Citations

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  • Gene Editing with CRISPR/Cas Methodology and Thyroid Cancer: Where Are We?
    Cesar Seigi Fuziwara, Diego Claro de Mello, Edna Teruko Kimura
    Cancers.2022; 14(3): 844.     CrossRef
  • Extracellular Vesicles as Signal Carriers in Malignant Thyroid Tumors?
    Małgorzata Grzanka, Anna Stachurska-Skrodzka, Anna Adamiok-Ostrowska, Ewa Gajda, Barbara Czarnocka
    International Journal of Molecular Sciences.2022; 23(6): 3262.     CrossRef
  • Mitofusin-2 modulates the epithelial to mesenchymal transition in thyroid cancer progression
    Mi-Hyeon You, Min Ji Jeon, Seong ryeong Kim, Woo Kyung Lee, Sheue-yann Cheng, Goo Jang, Tae Yong Kim, Won Bae Kim, Young Kee Shong, Won Gu Kim
    Scientific Reports.2021;[Epub]     CrossRef
  • High Phosphoglycerate Dehydrogenase Expression Induces Stemness and Aggressiveness in Thyroid Cancer
    Min Ji Jeon, Mi-Hyeon You, Ji Min Han, Soyoung Sim, Hyun Ju Yoo, Woo Kyung Lee, Tae Yong Kim, Dong Eun Song, Young Kee Shong, Won Gu Kim, Won Bae Kim
    Thyroid.2020; 30(11): 1625.     CrossRef
Thyroid
Clinical Outcomes of Differentiated Thyroid Cancer Patients with Local Recurrence or Distant Metastasis Detected in Old Age
Ji Min Han, Ji Cheol Bae, Hye In Kim, Sam Kwon, Min Ji Jeon, Won Gu Kim, Tae Yong Kim, Young Kee Shong, Won Bae Kim
Endocrinol Metab. 2018;33(4):459-465.   Published online November 30, 2018
DOI: https://doi.org/10.3803/EnM.2018.33.4.459
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AbstractAbstract PDFPubReader   ePub   CrossRef-TDMCrossref - TDM
Background

Differentiated thyroid carcinoma (DTC) shows a very good prognosis, but older patients have a higher recurrence rate and those show poor prognosis than younger patients. The aim of this study was to determine the clinical outcomes of thyroid cancer patients who experienced recurrence in old age according to the treatment strategy used.

Methods

This retrospective observational cohort study was conducted at Asan Medical Center, Seoul, Korea. Among DTC patients with no evidence of disease after initial treatment, we enrolled 86 patients who experienced recurrence at an age >65 years from 1994 to 2012. Sixty-nine patients had local recurrence and 17 patients showed distant metastasis.

Results

The mean age of patients at recurrence was 72 years. Patients were followed up for a median of 4.1 years after recurrence. Sixty-three of the 69 patients with local recurrence received additional treatment, while the other six received conservative care. The cancer-specific mortality rate was 15.5% in the local recurrence group. Airway problems were the main cause of death in patients who did not receive further treatment for local recurrence. Among the 17 patients with distant metastasis, 10 underwent specific treatment for metastasis and seven received only supportive management. Seven of those 17 patients died, and the cancer-specific mortality rate was 35% in the distant metastasis group.

Conclusion

The overall cancer-specific mortality rate was 20% in DTC patients in whom recurrence was first detected at an age >65 years. Mortality due to uncontrolled local disease occurred frequently in patients who did not receive definitive management for recurrence.

Citations

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  • Identification of Circulating Tumor Cell Phenotype in Differentiated Thyroid Carcinoma
    Huiling Wang, Mian Lv, Yonghong Huang, Xiaoming Pan, Changyuan Wei
    Journal of Biomaterials and Tissue Engineering.2022; 12(4): 813.     CrossRef
  • Long-Term Outcomes and Prognoses of Elderly Patients (≥65-Years-Old) With Distant Metastases From Well-Differentiated Thyroid Cancer During Radioiodine Therapy and Follow-Up
    Zhong-Ling Qiu, Chen-Tian Shen, Zhen-Kui Sun, Hong-Jun Song, Chuang Xi, Guo-Qiang Zhang, Yang Wang, Quan-Yong Luo
    Frontiers in Endocrinology.2021;[Epub]     CrossRef
  • Head-to-Head Comparison of Neck 18F-FDG PET/MR and PET/CT in the Diagnosis of Differentiated Thyroid Carcinoma Patients after Comprehensive Treatment
    Yangmeihui Song, Fang Liu, Weiwei Ruan, Fan Hu, Muhsin H. Younis, Zairong Gao, Jie Ming, Tao Huang, Weibo Cai, Xiaoli Lan
    Cancers.2021; 13(14): 3436.     CrossRef
  • Highly sensitive electrochemical immunosensor using a protein-polyvinylidene fluoride nanocomposite for human thyroglobulin
    Maria Oneide Silva de Moraes, João de Deus Pereira de Moraes Segundo, Marcos Marques da Silva Paula, Maria Goreti Ferreira Sales, Walter Ricardo Brito
    Bioelectrochemistry.2021; 142: 107888.     CrossRef
Thyroid
Comparison of Immunohistochemistry and Direct Sanger Sequencing for Detection of the BRAFV600E Mutation in Thyroid Neoplasm
Hye-Seon Oh, Hyemi Kwon, Suyeon Park, Mijin Kim, Min Ji Jeon, Tae Yong Kim, Young Kee Shong, Won Bae Kim, Jene Choi, Won Gu Kim, Dong Eun Song
Endocrinol Metab. 2018;33(1):62-69.   Published online January 30, 2018
DOI: https://doi.org/10.3803/EnM.2018.33.1.62
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   CrossRef-TDMCrossref - TDM
Background

The BRAFV600E mutation is the most common genetic alteration identified in papillary thyroid carcinoma (PTC). Because of its costs effectiveness and sensitivity, direct Sanger sequencing has several limitations. The aim of this study was to evaluate the efficiency of immunohistochemistry (IHC) as an alternative method to detect the BRAFV600E mutation in preoperative and postoperative tissue samples.

Methods

We evaluated 71 patients who underwent thyroid surgery with the result of direct sequencing of the BRAFV600E mutation. IHC staining of the BRAFV600E mutation was performed in 49 preoperative and 23 postoperative thyroid specimens.

Results

Sixty-two patients (87.3%) had PTC, and of these, BRAFV600E was confirmed by direct sequencing in 57 patients (91.9%). In 23 postoperative tissue samples, the BRAFV600E mutation was detected in 16 samples (70%) by direct sequencing and 18 samples (78%) by IHC. In 24 fine needle aspiration (FNA) samples, BRAFV600E was detected in 18 samples (75%) by direct sequencing and 16 samples (67%) by IHC. In 25 core needle biopsy (CNB) samples, the BRAFV600E mutation was detected in 15 samples (60%) by direct sequencing and 16 samples (64%) by IHC. The sensitivity and specificity of IHC for detecting the BRAFV600E mutation were 77.8% and 66.7% in FNA samples and 99.3% and 80.0% in CNB samples.

Conclusion

IHC could be an alternative method to direct Sanger sequencing for BRAFV600E mutation detection both in postoperative and preoperative samples. However, application of IHC to detect the BRAFV600E mutation in FNA samples is of limited value compared with direct sequencing.

Citations

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  • An effective approach for BRAF V600E mutation analysis of routine thyroid fine needle aspirates
    Tanupriya Agrawal, Liqiang Xi, Winnifred Navarro, Mark Raffeld, Snehal B. Patel, Mark J. Roth, Joanna Klubo‐Gwiezdzinska, Armando C. Filie
    Cytopathology.2022; 33(3): 344.     CrossRef
  • A dual identification strategy based on padlock ligation and CRISPR/Cas14a for highly specific detection of BRAF V600E mutation in clinical samples
    Weicheng Shi, Yao Gong, Decai Zhang, Tiantian Yang, Ming Yi, Jingyi Tan, Shijia Ding, Wei Cheng
    Analytical Methods.2022; 14(19): 1913.     CrossRef
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    延泽 刘
    Advances in Clinical Medicine.2022; 12(09): 8499.     CrossRef
  • VE1 immunohistochemistry is an adjunct tool for detection of BRAF V600E mutation: Validation in thyroid cancer patients
    Faiza A. Rashid, Sobia Tabassum, Mosin S. Khan, Hifzur R. Ansari, Muhammad Asif, Ahmareen K. Sheikh, Syed Aga
    Journal of Clinical Laboratory Analysis.2021;[Epub]     CrossRef
  • BRAF testing in a South African cohort of MLH1 deficient endometrial carcinomas: lessons learnt
    Reubina Wadee, Wayne Grayson
    Southern African Journal of Gynaecological Oncology.2021; 13(1): 1.     CrossRef
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    Changwen Jing, Haixia Cao, Rong Ma, Jianzhong Wu, Zhuo Wang
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  • Development of a Molecular Assay for Detection and Quantification of the BRAF Variation in Residual Tissue From Thyroid Nodule Fine-Needle Aspiration Biopsy Specimens
    Guodong Fu, Ronald S. Chazen, Christina MacMillan, Ian J. Witterick
    JAMA Network Open.2021; 4(10): e2127243.     CrossRef
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    Faiza Rashid, Ghulam Bhat, Mosin Khan, Sobia Tabassum, Mohammad Bhat
    Molecular and Clinical Oncology.2021;[Epub]     CrossRef
  • Evaluation of the expression levels of BRAFV600E mRNA in primary tumors of thyroid cancer using an ultrasensitive mutation assay
    Tien Viet Tran, Kien Xuan Dang, Quynh Huong Pham, Ung Dinh Nguyen, Nhung Thi Trang Trinh, Luong Van Hoang, Son Anh Ho, Ba Van Nguyen, Duc Trong Nguyen, Dung Tuan Trinh, Dung Ngoc Tran, Arto Orpana, Ulf-Håkan Stenman, Jakob Stenman, Tho Huu Ho
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  • VE1 Immunohistochemistry Improves the Limit of Genotyping for Detecting BRAFV600E Mutation in Papillary Thyroid Cancer
    Sonam Choden, Somboon Keelawat, Chan Kwon Jung, Andrey Bychkov
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  • Comparison of Molecular Methods and BRAF Immunohistochemistry (VE1 Clone) for the Detection of BRAF V600E Mutation in Papillary Thyroid Carcinoma: A Meta-Analysis
    Kyle G. Parker, Michael G. White, Nicole A. Cipriani
    Head and Neck Pathology.2020; 14(4): 1067.     CrossRef
  • Next generation sequencing based detection of 15 target genes mutations in papillary thyroid carcinoma
    Zhuo Wang, Changwen Jing, Haixia Cao, SiWen Liu, Jianzhong Wu, Rong Ma
    Precision Medical Sciences.2020; 9(2): 90.     CrossRef
  • A Systematic Review and Meta-Analysis of the Diagnostic Performance of BRAF V600E Immunohistochemistry in Thyroid Histopathology
    Ranjit Singarayer, Ozgur Mete, Laure Perrier, Lehana Thabane, Sylvia L. Asa, Stan Van Uum, Shereen Ezzat, David P. Goldstein, Anna M. Sawka
    Endocrine Pathology.2019; 30(3): 201.     CrossRef
  • Comparison of droplet digital PCR and direct Sanger sequencing for the detection of the BRAF V600E mutation in papillary thyroid carcinoma
    Zhuo Wang, Kejing Sun, Changwen Jing, Haixia Cao, Rong Ma, Jianzhong Wu
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    Narittee Sukswai, Joseph D. Khoury
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  • Immunohistochemistry is a feasible method to screen BRAF V600E mutation in colorectal and papillary thyroid carcinoma
    Xiangyan Zhang, Lili Wang, Jigang Wang, Han Zhao, Jie Wu, Shuhong Liu, Lu Zhang, Yujun Li, Xiaoming Xing
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Clinical Study
Disease-Specific Mortality of Differentiated Thyroid Cancer Patients in Korea: A Multicenter Cohort Study
Min Ji Jeon, Won Gu Kim, Tae Hyuk Kim, Hee Kyung Kim, Bo Hyun Kim, Hyon-Seung Yi, Eun Sook Kim, Hosu Kim, Young Nam Kim, Eun Heui Kim, Tae Yong Kim, Sun Wook Kim, Ho-Cheol Kang, Jae Hoon Chung, Young Kee Shong, Won Bae Kim
Endocrinol Metab. 2017;32(4):434-441.   Published online November 22, 2017
DOI: https://doi.org/10.3803/EnM.2017.32.4.434
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AbstractAbstract PDFSupplementary MaterialPubReader   CrossRef-TDMCrossref - TDM
Background

Little is known regarding disease-specific mortality of differentiated thyroid cancer (DTC) patients and its risk factors in Korea.

Methods

We retrospectively reviewed a large multi-center cohort of thyroid cancer from six Korean hospitals and included 8,058 DTC patients who underwent initial surgery between 1996 and 2005.

Results

Mean age of patients at diagnosis was 46.2±12.3 years; 87% were females. Most patients had papillary thyroid cancer (PTC; 97%) and underwent total thyroidectomy (85%). Mean size of the primary tumor was 1.6±1.0 cm. Approximately 40% of patients had cervical lymph node (LN) metastases and 1.3% had synchronous distant metastases. During 11.3 years of follow-up, 150 disease-specific mortalities (1.9%) occurred; the 10-year disease-specific survival (DSS) rate was 98%. According to the year of diagnosis, the number of disease-specific mortality was not different. However, the rate of disease-specific mortality decreased during the study period (from 7.7% to 0.7%). Older age (≥45 years) at diagnosis, male, follicular thyroid cancer (FTC) versus PTC, larger tumor size (>2 cm), presence of extrathyroidal extension (ETE), lateral cervical LN metastasis, distant metastasis and tumor node metastasis (TNM) stage were independent risk factors of disease-specific mortality of DTC patients.

Conclusion

The rate of disease-specific mortality of Korean DTC patients was 1.9%; the 10-year DSS rate was 98% during 1996 to 2005. Older age at diagnosis, male, FTC, larger tumor size, presence of ETE, lateral cervical LN metastasis, distant metastasis, and TNM stages were significant risk factors of disease-specific mortality of Korean DTC patients.

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  • Log odds of negative lymph nodes/T stage ratio (LONT): A new prognostic tool for differentiated thyroid cancer without metastases in patients aged 55 and older
    Xuezhen Wang, Yufan Wu, Xiaoxia Li, Jinsheng Hong, Mingwei Zhang
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • Outcomes of Advanced Medullary Thyroid Carcinoma in the Era of Targeted Therapy
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Thyroid Stimulating Hormone Reference Range and Prevalence of Thyroid Dysfunction in the Korean Population: Korea National Health and Nutrition Examination Survey 2013 to 2015
Won Gu Kim, Won Bae Kim, Gyeongji Woo, Hyejin Kim, Yumi Cho, Tae Yong Kim, Sun Wook Kim, Myung-Hee Shin, Jin Woo Park, Hai-Lin Park, Kyungwon Oh, Jae Hoon Chung
Endocrinol Metab. 2017;32(1):106-114.   Published online January 23, 2017
DOI: https://doi.org/10.3803/EnM.2017.32.1.106
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AbstractAbstract PDFPubReader   CrossRef-TDMCrossref - TDM
Background

No nationwide epidemiological study evaluating the prevalence of subclinical and overt forms of hypothyroidism and hyperthyroidism has yet been conducted in Korea. This study aimed to evaluate the reference range of serum thyroid stimulating hormone (TSH) and the national prevalence of thyroid dysfunctions in Korea.

Methods

Nation-wide cross-sectional data were analyzed from a representative sample of the civilian, non-institutionalized Korean population (n=6,564) who underwent blood testing for thyroid function and anti-thyroid peroxidase antibody (TPOAb) as part of the Korea National Health and Nutrition Examination Survey VI (2013 to 2015).

Results

The reference interval of serum TSH in the Korean reference population was 0.62 to 6.68 mIU/L. Based on this reference interval, the prevalence of overt and subclinical hypothyroidism was 0.73% (males 0.40%, females 1.10%) and 3.10% (males 2.26%, females 4.04%), respectively. The prevalence of hypothyroidism increased with age until the age group between 50 to 59 years. Positive TPOAb were found in 7.30% of subjects (males 4.33%, females 10.62%). The prevalence of overt and subclinical hypothyroidism TPOAb-positive subjects was 5.16% and 10.88%, respectively. The prevalence of overt and subclinical hyperthyroidism was 0.54% (males 0.30%, females 0.81%) and 2.98% (males 2.43%, females, 3.59%), respectively.

Conclusion

The Serum TSH reference levels in the Korean population were higher than the corresponding levels in Western countries. Differences were found in the prevalence of hypothyroidism and hyperthyroidism according to age, sex, and TPOAb positivity. This study provides important baseline information for understanding patterns of thyroid dysfunction and diseases in Korea.

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    Endocrinology and Metabolism.2017; 32(2): 304.     CrossRef
  • Excessive Iodine Intake and Thyrotropin Reference Interval: Data from the Korean National Health and Nutrition Examination Survey
    Min Ji Jeon, Won Gu Kim, Hyemi Kwon, Mijin Kim, Suyeon Park, Hye-Seon Oh, Minkyu Han, Tae Yong Kim, Young Kee Shong, Won Bae Kim
    Thyroid.2017; 27(7): 967.     CrossRef
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    Hosu Kim, Tae Hyuk Kim, Hye In Kim, So Young Park, Young Nam Kim, Seonwoo Kim, Min-Ji Kim, Sang-Man Jin, Kyu Yeon Hur, Jae Hyeon Kim, Moon-Kyu Lee, Yong-Ki Min, Jae Hoon Chung, Mira Kang, Sun Wook Kim, Tatsuo Shimosawa
    PLOS ONE.2017; 12(7): e0182090.     CrossRef
  • Letter: Thyroid Stimulating Hormone Reference Range and Prevalence of Thyroid Dysfunction in the Korean Population: Korea National Health and Nutrition Examination Survey 2013 to 2015 (Endocrinol Metab 2017;32:106-14, Won Gu Kim et al.)
    Young Ki Lee, Dong Yeob Shin
    Endocrinology and Metabolism.2017; 32(2): 302.     CrossRef
  • Vitamin D deficiency affects thyroid autoimmunity and dysfunction in iodine-replete area: Korea national health and nutrition examination survey
    Mijin Kim, Eyun Song, Hye-Seon Oh, Suyeon Park, Hyemi Kwon, Min Ji Jeon, Won Gu Kim, Won Bae Kim, Young Kee Shong, Tae Yong Kim
    Endocrine.2017; 58(2): 332.     CrossRef
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    Stella C Pak, Yaseen Alastal, Zubair Khan, Umar Darr
    Euroasian Journal of Hepato-Gastroenterology.2017; 7(2): 163.     CrossRef
Clinical Study
Molecular Diagnosis Using Residual Liquid-Based Cytology Materials for Patients with Nondiagnostic or Indeterminate Thyroid Nodules
Hyemi Kwon, Won Gu Kim, Markus Eszlinger, Ralf Paschke, Dong Eun Song, Mijin Kim, Suyeon Park, Min Ji Jeon, Tae Yong Kim, Young Kee Shong, Won Bae Kim
Endocrinol Metab. 2016;31(4):586-591.   Published online November 4, 2016
DOI: https://doi.org/10.3803/EnM.2016.31.4.586
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AbstractAbstract PDFPubReader   CrossRef-TDMCrossref - TDM
Background

Molecular analysis for common somatic mutations in thyroid cancer can improve diagnostic accuracy of fine-needle aspiration cytology (FNAC) in the nondiagnostic or indeterminate category of thyroid nodules. In this study, we evaluated the feasibility of molecular diagnosis from residual liquid-based cytology (LBC) material after cytological diagnosis.

Methods

This prospective study enrolled 53 patients with thyroid nodules diagnosed as nondiagnostic, atypia of undetermined significance (AUS), or follicular lesion of undetermined significance (FLUS) after FNAC. DNAs and RNAs were isolated from residual LBC materials. BRAFV600E and RAS point mutations, PAX8/peroxisome proliferator-activated receptor γ (PPARγ), RET/PTC1, and RET/PTC3 rearrangements were evaluated by real-time polymerase chain reaction and pyrosequencing.

Results

All DNAs from 53 residual LBC samples could be analysed and point mutations were detected in 10 samples (19%). In 17 AUS nodules, seven samples (41%) had point mutations including BRAF (n=4), NRAS (n=2), and KRAS (n=1). In 20 FLUS nodules, three samples (15%) had NRAS point mutations. RNA from only one FLUS nodule could be analysed for rearrangements and there was no abnormality.

Conclusion

Molecular analysis for BRAF and RAS mutations was feasible in residual LBC materials and might be useful for diagnosis of indeterminate thyroid nodules.

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    Masahiro Itonaga, Reiko Ashida, Shin-Ichi Murata, Yasunobu Yamashita, Keiichi Hatamaru, Takashi Tamura, Yuki Kawaji, Yuudai Kayama, Tomoya Emori, Manabu Kawai, Hiroki Yamaue, Ibu Matsuzaki, Hirokazu Nagai, Yuichi Kinoshita, Ke Wan, Toshio Shimokawa, Masay
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    EMJ Oncology.2020;[Epub]     CrossRef
  • Preanalytic variables in quality and quantity of nucleic acids extracted from FNA specimens of thyroid gland nodules collected in CytoLyt: Cellularity and storage time
    Jonas J. Heymann, Lorene M. Yoxtheimer, Hyeon Jin Park, Evan M. Fernandez, Kirk E. Facey, Susan A. Alperstein, Hung V. Tran, Inji Baek, Theresa Scognamiglio, Hanna Rennert, Momin T. Siddiqui, Wei Song
    Cancer Cytopathology.2020; 128(9): 656.     CrossRef
  • Diagnostic accuracy of molecular testing with three molecular markers on thyroid fine‐needle aspiration cytology with abnormal category
    Hatice Seneldir, Gozde Kir, Tuce Soylemez, Rabia B. Girgin, Nurver Ozbay, Filiz Ozen, Handan Ankarali, Gurhan Bas, Orhan Alimoglu
    Diagnostic Cytopathology.2020; 48(6): 507.     CrossRef
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    Qiong Gan, Sinchita Roy-Chowdhuri
    Journal of the American Society of Cytopathology.2020; 9(5): 450.     CrossRef
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    Wenrui Ye, Brette Hannigan, Stephanie Zalles, Meenakshi Mehrotra, Bedia A. Barkoh, Michelle D. Williams, Maria E. Cabanillas, Beth Edeiken‐Monroe, Peter Hu, Dzifa Duose, Ignacio I. Wistuba, L. Jeffrey Medeiros, John Stewart, Rajyalakshmi Luthra, Sinchita
    Cancer Cytopathology.2019; 127(3): 146.     CrossRef
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    Sinchita Roy‐Chowdhuri
    Cancer Cytopathology.2019; 127(1): 15.     CrossRef
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    Yoko Sekita-Hatakeyama, Takeshi Nishikawa, Mao Takeuchi, Kouhei Morita, Maiko Takeda, Kinta Hatakeyama, Tokiko Nakai, Tomoko Uchiyama, Hiroe Itami, Tomomi Fujii, Akira Mitoro, Masayuki Sho, Chiho Ohbayashi, Giancarlo Troncone
    PLOS ONE.2018; 13(3): e0193692.     CrossRef
  • Comparison of Immunohistochemistry and Direct Sanger Sequencing for Detection of theBRAFV600EMutation in Thyroid Neoplasm
    Hye-Seon Oh, Hyemi Kwon, Suyeon Park, Mijin Kim, Min Ji Jeon, Tae Yong Kim, Young Kee Shong, Won Bae Kim, Jene Choi, Won Gu Kim, Dong Eun Song
    Endocrinology and Metabolism.2018; 33(1): 62.     CrossRef
  • Next-Generation Sequencing Identifies Gene Mutations That Are Predictive of Malignancy in Residual Needle Rinses Collected From Fine-Needle Aspirations of Thyroid Nodules
    Maren Y. Fuller, Dina Mody, April Hull, Kristi Pepper, Heather Hendrickson, Randall Olsen
    Archives of Pathology & Laboratory Medicine.2018; 142(2): 178.     CrossRef
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    Won-Young Lee
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  • Loss of c-KIT expression in thyroid cancer cells
    Sara Franceschi, Francesca Lessi, Federica Panebianco, Elena Tantillo, Marco La Ferla, Michele Menicagli, Paolo Aretini, Alessandro Apollo, Antonio Giuseppe Naccarato, Ivo Marchetti, Chiara Maria Mazzanti, Aamir Ahmad
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Endocrine Research
Comparison of Thyroglobulin Measurements Using Three Different Immunoassay Kits: A BRAMHS Tg-Plus RIA Kit, a BRAMHS hTg Sensitive Kryptor Kit, and a Beckman Coulter ACCESS Immunoassay Kit
Mijin Kim, Min Ji Jeon, Won Gu Kim, Jong Jin Lee, Jin-Sook Ryu, Eun-Jung Cho, Dae-Hyun Ko, Woochang Lee, Sail Chun, Won-Ki Min, Tae Yong Kim, Young Kee Shong, Won Bae Kim
Endocrinol Metab. 2016;31(3):462-468.   Published online August 2, 2016
DOI: https://doi.org/10.3803/EnM.2016.31.3.462
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  • 7 Citations
AbstractAbstract PDFPubReader   CrossRef-TDMCrossref - TDM
Background

Second-generation thyroglobulin immunometric assays (Tg-IMAs) have been developed with improved sensitivity. Our aim was to compare the diagnostic value of Tg-IMA measurements using a Kryptor (BRAHMS AG) kit (Tg-K) and an ACCESS (Beckman Coulter) kit (Tg-A) with that of the first-generation Tg measurement using a Tg-plus (BRAHMS AG) kit (Tg+).

Methods

We enrolled 82 differentiated thyroid cancer patients who underwent total thyroidectomy with radioactive iodine remnant ablation and who underwent diagnostic whole body scan using recombinant human thyroid stimulating hormone (rhTSH). The Tg+, Tg-K, and Tg-A were measured before rhTSH administration during levothyroxine treatment (suppressed Tg) from the same sample. Serum Tg+ was measured after rhTSH stimulation (stimulated Tg).

Results

Suppressed Tg+ was more significantly correlated with suppressed Tg-K (R2=0.919, P<0.001) than with suppressed Tg-A (R2=0.536, P<0.001). The optimal cut-off values of suppressed Tg+, Tg-K, and Tg-A for predicting stimulated Tg+ of 1 ng/mL were 0.3, 0.2, and 0.2 ng/mL, respectively. The sensitivity, specificity, and accuracy of suppressed Tg+ were 67%, 100%, and 90%, respectively; those of suppressed Tg-K were 83%, 90%, and 88%; those of suppressed Tg-A were 96%, 82%, and 87%, respectively. The positive predictive and negative predictive values of Tg+ were 100% and 87%, respectively; those of Tg-K were 79% and 92%; and those of Tg-A were 73% and 98%.

Conclusion

We could not clearly demonstrate which kit had better diagnostic performance after comparison of first-generation Tg measurements with Tg-IMA measurements. Also, there were kit-to-kit variations between Tg-IMA kits. Suppressed Tg measured by Tg-IMA was insufficient to completely substitute for a stimulated Tg measurement.

Citations

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  • Comparison of the diagnostic performances of US-guided fine needle aspiration cytology and thyroglobulin measurement for lymph node metastases in patients with differentiated thyroid carcinoma: a meta-analysis
    Rong-Bin Liu, Da-Lei Zhou, Bo-Heng Xu, Xin-Hua Yang, Qing Liu, Xiao Zhang, Tao Tang, Zu-Lu Ye, Yue Li
    European Radiology.2021; 31(5): 2903.     CrossRef
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    Hosu Kim, So Young Park, Jun-Ho Choe, Jee Soo Kim, Soo Yeon Hahn, Sun Wook Kim, Jae Hoon Chung, Jaehoon Jung, Tae Hyuk Kim
    Cancers.2020; 12(3): 625.     CrossRef
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    Eyun Song, Jonghwa Ahn, Min Ji Jeon, Sang Min Lee, Jeong Hyun Lee, Tae Yong Kim, Jung Hwan Baek, Won Bae Kim, Young Kee Shong, Won Gu Kim
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  • Impact of delayed radioiodine therapy in intermediate‐/high‐risk papillary thyroid carcinoma
    Mijin Kim, Minkyu Han, Min Ji Jeon, Won Gu Kim, In Joo Kim, Jin‐Sook Ryu, Won Bae Kim, Young Kee Shong, Tae Yong Kim, Bo Hyun Kim
    Clinical Endocrinology.2019; 91(3): 449.     CrossRef
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    Mijin Kim, Tae Hyuk Kim, Dong Yeob Shin, Dong Jun Lim, Eui Young Kim, Won Bae Kim, Jae Hoon Chung, Young Kee Shong, Bo Hyun Kim, Won Gu Kim
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    Min Ji Jeon, Mijin Kim, Suyeon Park, Hye-Seon Oh, Tae Yong Kim, Won Bae Kim, Young Kee Shong, Won Gu Kim
    Thyroid.2018; 28(2): 187.     CrossRef
  • Preoperative serum thyroglobulin predicts initial distant metastasis in patients with differentiated thyroid cancer
    Hosu Kim, Young Nam Kim, Hye In Kim, So Young Park, Jun-Ho Choe, Jung-Han Kim, Jee Soo Kim, Jae Hoon Chung, Tae Hyuk Kim, Sun Wook Kim
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Clinical Study
Usefulness of Measuring Thyroid Stimulating Antibody at the Time of Antithyroid Drug Withdrawal for Predicting Relapse of Graves Disease
Hyemi Kwon, Won Gu Kim, Eun Kyung Jang, Mijin Kim, Suyeon Park, Min Ji Jeon, Tae Yong Kim, Jin-Sook Ryu, Young Kee Shong, Won Bae Kim
Endocrinol Metab. 2016;31(2):300-310.   Published online April 25, 2016
DOI: https://doi.org/10.3803/EnM.2016.31.2.300
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  • 16 Citations
AbstractAbstract PDFPubReader   CrossRef-TDMCrossref - TDM
Background

Hyperthyroidism relapse in Graves disease after antithyroid drug (ATD) withdrawal is common; however, measuring the thyrotropin receptor antibody (TRAb) at ATD withdrawal in order to predict outcomes is controversial. This study compared measurement of thyroid stimulatory antibody (TSAb) and thyrotropin-binding inhibitory immunoglobulin (TBII) at ATD withdrawal to predict relapse.

Methods

This retrospective study enrolled patients with Graves disease who were treated with ATDs and whose serum thyroid-stimulating hormone levels were normal after receiving low-dose ATDs. ATD therapy was stopped irrespective of TRAb positivity after an additional 6 months of receiving the minimum dose of ATD therapy. Patients were followed using thyroid function tests and TSAb (TSAb group; n=35) or TBII (TBII group; n=39) every 3 to 6 months for 2 years after ATD withdrawal.

Results

Twenty-eight patients (38%) relapsed for a median follow-up of 21 months, and there were no differences in baseline clinical characteristics between groups. In the TSAb group, relapse was more common in patients with positive TSAb at ATD withdrawal (67%) than patients with negative TSAb (17%; P=0.007). Relapse-free survival was shorter in TSAb-positive patients. In the TBII group, there were no differences in the relapse rate and relapse-free survivals according to TBII positivity. For predicting Graves disease relapse, the sensitivity and specificity of TSAb were 63% and 83%, respectively, whereas those of TBII were 28% and 65%.

Conclusion

TSAb at ATD withdrawal can predict the relapse of Graves hyperthyroidism, but TBII cannot. Measuring TSAb at ATD withdrawal can assist with clinical decisions making for patients with Graves disease.

Citations

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  • Thyroid-Stimulatory Antibody as a Predictive Factor for Graves’ Disease Relapse
    Tiago Da Silva Santos, José Carlos Oliveira, Cláudia Freitas, André Couto de Carvalho
    Cureus.2022;[Epub]     CrossRef
  • The Prediction Model Using Thyroid-stimulating Immunoglobulin Bioassay For Relapse of Graves’ Disease
    Han-Sang Baek, Jaejun Lee, Chai-Ho Jeong, Jeongmin Lee, Jeonghoon Ha, Kwanhoon Jo, Min-Hee Kim, Jae Hyoung Cho, Moo Il Kang, Dong-Jun Lim
    Journal of the Endocrine Society.2022;[Epub]     CrossRef
  • Identification of patients with Graves’ disease who benefit from high-dose radioactive iodine therapy
    Shiro Watanabe, Shozo Okamoto, Kazumasa Akikawa, Noriyuki Miyamoto, Miyuki Okamura-Kawasaki, Yuko Uchiyama, Junki Takenaka, Takuya Toyonaga, Kenji Hirata, Kohsuke Kudo
    Annals of Nuclear Medicine.2022; 36(11): 923.     CrossRef
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    Xinxin Zhu, Yaguang Zhang, Xiaoyu Zhao, Xiaona Zhang, Zixuan Ru, Yanmeizhi Wu, Xu Yang, Boyu Hou, Hong Qiao
    Frontiers in Cardiovascular Medicine.2022;[Epub]     CrossRef
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    Jae Hoon Chung
    Endocrinology and Metabolism.2021; 36(3): 491.     CrossRef
  • The prognostic value of thyroid-stimulating immunoglobulin in the management of Graves’ disease
    Yulin Zhou, Mengxi Zhou, Yicheng Qi, Weiqing Wang, Xinxin Chen, Shu Wang
    Therapeutic Advances in Endocrinology and Metabolism.2021; 12: 204201882110449.     CrossRef
  • Changes in Thyroid Peroxidase and Thyroglobulin Antibodies Might Be Associated with Graves' Disease Relapse after Antithyroid Drug Therapy
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    Wilmar M. Wiersinga
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    Hyun-Kyung Chung
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  • When should antithyroid drug therapy to reduce the relapse rate of hyperthyroidism in Graves’ disease be discontinued?
    Suyeon Park, Eyun Song, Hye-Seon Oh, Mijin Kim, Min Ji Jeon, Won Gu Kim, Tae Yong Kim, Young Kee Shong, Doo Man Kim, Won Bae Kim
    Endocrine.2019; 65(2): 348.     CrossRef
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    Jianhui Li, Xiaohua Sun, Danzhen Yao, Jinying Xia
    International Journal of Endocrinology.2018; 2018: 1.     CrossRef
  • Active Surveillance for Patients With Papillary Thyroid Microcarcinoma: A Single Center’s Experience in Korea
    Hyemi Kwon, Hye-Seon Oh, Mijin Kim, Suyeon Park, Min Ji Jeon, Won Gu Kim, Won Bae Kim, Young Kee Shong, Dong Eun Song, Jung Hwan Baek, Ki-Wook Chung, Tae Yong Kim
    The Journal of Clinical Endocrinology & Metabolism.2017; 102(6): 1917.     CrossRef
  • Free Thyroxine, Anti-Thyroid Stimulating Hormone Receptor Antibody Titers, and Absence of Goiter Were Associated with Responsiveness to Methimazole in Patients with New Onset Graves' Disease
    Hoon Sung Choi, Won Sang Yoo
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  • The Second Antithyroid Drug Treatment Is Effective in Relapsed Graves' Disease Patients: A Median 11-Year Follow-Up Study
    Ye An Kim, Sun Wook Cho, Hoon Sung Choi, Shinje Moon, Jae Hoon Moon, Kyung Won Kim, Do Joon Park, Ka Hee Yi, Young Joo Park, Bo Youn Cho
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  • The Recurrence Rate of Graves' Disease among Patients with Subclinical Thyrotoxicosis after Initial Remission with Antithyroid Agents
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Clinical Study
Low Prevalence of Somatic TERT Promoter Mutations in Classic Papillary Thyroid Carcinoma
Min Ji Jeon, Won Gu Kim, Soyoung Sim, Seonhee Lim, Hyemi Kwon, Tae Yong Kim, Young Kee Shong, Won Bae Kim
Endocrinol Metab. 2016;31(1):100-104.   Published online March 16, 2016
DOI: https://doi.org/10.3803/EnM.2016.31.1.100
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  • 28 Download
  • 15 Citations
AbstractAbstract PDFPubReader   CrossRef-TDMCrossref - TDM
Background

Transcriptional activating mutations of telomerase reverse transcriptase (TERT) are associated with more aggressive thyroid cancer. We evaluated the significance of TERT promoter mutations in Korean patients with classic papillary thyroid cancer (PTC).

Methods

Genomic DNA was isolated from four thyroid cancer cell lines and 35 fresh-frozen PTC tissues. TERT promoter mutations (C228T and C250T) and the BRAF V600E mutation were evaluated by polymerase chain reaction amplification and direct sequencing.

Results

The CC228229TT mutation in the TERT promoter was detected in BCPAP cells and the C250T mutation was found in 8505C cells. No TERT promoter mutation was observed in Cal-62 or ML-1 cells. The C228T mutation was found in only 1 of 35 (2.8%) PTCs and no C250T mutations were detected in any of the study subjects. The BRAF V600E mutation was found in 20 of 35 (57.1%) PTCs. One patient with the C228T TERT mutation also harbored the BRAF V600E mutation and developed a recurrence.

Conclusion

The prevalence of somatic TERT promoter mutations was low in Korean patients with classic PTC. Therefore, the prognostic role of TERT promoter mutations might be limited in this patient cohort.

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    Jingxin Mao, Xingliang Huang, Mohammad K. Okla, Mostafa A. Abdel-Maksoud, Ayman Mubarak, Zahid Hameed, Razia Noreen, Aqsa Chaudhary, Shakira Ghazanfar, Yixuan Liao, Yasir Hameed, Chen Li, Min Tang
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  • Telomerase reverse transcriptase promoter mutations in cancers derived from multiple organ sites among middle eastern population
    Abdul K. Siraj, Rong Bu, Kaleem Iqbal, Sandeep Kumar Parvathareddy, Nabil Siraj, Sarah Siraj, Mark Ranier F. Diaz, Dionne Rae Rala, Allianah D. Benito, Maria Angelita Sabido, Maha Al-Rasheed, Khadija A.S. Al-Obaisi, Wael Al-Haqawi, Ingrid G. Victoria, Waf
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    Jing Yang, Yanping Gong, Shuping Yan, Hui Chen, Siqin Qin, Rixiang Gong
    Endocrine.2020; 67(1): 44.     CrossRef
  • The Combination of RET, BRAF and Demographic Data Identifies Subsets of Patients with Aggressive Papillary Thyroid Cancer
    Jose R. W. Martínez, Sergio Vargas-Salas, Soledad Urra Gamboa, Estefanía Muñoz, José Miguel Domínguez, Augusto León, Nicolás Droppelmann, Antonieta Solar, Mark Zafereo, F. Christopher Holsinger, Hernán E. González
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    Jiangqiao Geng, Yuanhu Liu, Yongli Guo, Huanmin Wang, Jun Tai, Yaqiong Jin, Jie Zhang, Yongbo Yu, Shengcai Wang, Yingluan Song, Xin Ni
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    Valentina Maggisano, Marilena Celano, Saverio Massimo Lepore, Marialuisa Sponziello, Francesca Rosignolo, Valeria Pecce, Antonella Verrienti, Federica Baldan, Catia Mio, Lorenzo Allegri, Marianna Maranghi, Rosa Falcone, Giuseppe Damante, Diego Russo, Stef
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  • BRAF and RAS Mutational Status in Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features and Invasive Subtype of Encapsulated Follicular Variant of Papillary Thyroid Carcinoma in Korea
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    Giovanni E. Lombardo, Valentina Maggisano, Marilena Celano, Donato Cosco, Chiara Mignogna, Federica Baldan, Saverio M. Lepore, Lorenzo Allegri, Sonia Moretti, Cosimo Durante, Giuseppe Damante, Massimo Fresta, Diego Russo, Stefania Bulotta, Efisio Puxeddu
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    Tiantian Liu, Xiaotian Yuan, Dawei Xu
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    Muhammad Ramlee, Jing Wang, Wei Toh, Shang Li
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Clinical Study
Thyrotoxic Periodic Paralysis and Polymorphisms of the ADRB2, AR, and GABRA3 Genes in Men with Graves Disease
Suyeon Park, Tae Yong Kim, Soyoung Sim, Seonhee Lim, Mijin Kim, Hyemi Kwon, Min Ji Jeon, Won Gu Kim, Young Kee Shong, Won Bae Kim
Endocrinol Metab. 2016;31(1):142-146.   Published online March 16, 2016
DOI: https://doi.org/10.3803/EnM.2016.31.1.142
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  • 31 Download
  • 4 Citations
AbstractAbstract PDFPubReader   CrossRef-TDMCrossref - TDM
Background

Thyrotoxic periodic paralysis (TPP) is a rare complication of thyrotoxicosis characterized by acute attacks of muscle weakness and hypokalemia. Recently, variation in several genes was suggested to be associated with TPP. This study evaluated the genetic predisposition to TPP in terms of the β2-adrenergic receptor (ADRB2), androgen receptor (AR), and γ-aminobutyric acid receptor α3 subunit (GABRA3) genes.

Methods

This study enrolled 48 men with Graves disease (GD) and TPP, and 48 GD patients without TPP. We compared the frequencies of candidate polymorphisms between the two groups.

Results

The frequency of the Gly16/Gly16 genotype in ADRB2 was not significantly associated with TPP (P=0.32). More CAG repeats (≥26) in the AR gene were not correlated with TPP (odds ratio [OR], 2.46; 95% confidence interval [CI], 0.81 to 8.09; P=0.08). The allele frequency of the TT genotype in the GABRA3 gene was not associated with TPP (OR, 1.83; 95% CI, 0.54 to 6.74; P=0.41).

Conclusion

The polymorphisms in the ADRB2, AR, and GABRA3 genes could not explain the genetic susceptibility to TPP in Korean men with GD.

Citations

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  • RNASET2 ,GPR174 , and PTPN22 gene polymorphisms are related to the risk of liver damage associated with the hyperthyroidism in patients with Graves’ disease
    Qing Zhang, Shaozheng Liu, Yanxing Guan, Qingjie Chen, Qing Zhang, Xiang Min
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Thyroid
Lack of Associations between Body Mass Index and Clinical Outcomes in Patients with Papillary Thyroid Carcinoma
Hyemi Kwon, Mijin Kim, Yun Mi Choi, Eun Kyung Jang, Min Ji Jeon, Won Gu Kim, Tae Yong Kim, Young Kee Shong, Dong Eun Song, Jung Hwan Baek, Suck Joon Hong, Won Bae Kim
Endocrinol Metab. 2015;30(3):305-311.   Published online November 26, 2014
DOI: https://doi.org/10.3803/EnM.2015.30.3.305
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AbstractAbstract PDFPubReader   CrossRef-TDMCrossref - TDM
Background

Obesity is associated with aggressive pathological features and poor clinical outcomes in breast and prostate cancers. In papillary thyroid carcinoma (PTC), these relationships remain still controversial. This study aimed to evaluate the associations between body mass index (BMI) and the clinical outcomes of patients with PTC.

Methods

This retrospective study included 1,189 patients who underwent total thyroidectomy for PTCs equal to or larger than 1 cm in size. Clinical outcomes were evaluated and compared based on the BMI quartiles.

Results

There were no significant associations between BMI quartiles and primary tumor size, extrathyroidal invasion, cervical lymph node metastasis, or distant metastasis. However, an increase in mean age was associated with an increased BMI (P for trend <0.001). Multifocality and advanced tumor-node-metastasis (TNM) stage (stage III or IV) were significantly associated with increases of BMI (P for trend 0.02 and <0.001, respectively). However, these associations of multifocality and advanced TNM stage with BMI were not significant in multivariate analyses adjusted for age and gender. Moreover, there were no differences in recurrence-free survivals according to BMI quartiles (P=0.26).

Conclusion

In the present study, BMI was not associated with the aggressive clinicopathological features or recurrence-free survivals in patients with PTC.

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Thyroid
A Closer Look at Papillary Thyroid Carcinoma
Won Bae Kim
Endocrinol Metab. 2015;30(1):1-6.   Published online March 27, 2015
DOI: https://doi.org/10.3803/EnM.2015.30.1.1
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AbstractAbstract PDFPubReader   CrossRef-TDMCrossref - TDM

Recent surge of thyroid cancer, especially papillary thyroid carcinoma (PTC), ignited a debate on over-diagnosis of cancer. Such increase in incidence is a worldwide phenomenon, but it has been the most prominent in Korea. Although increased detection might have played a major role, some evidences suggest that true increase in incidence have also contributed to such phenomenon. PTC is a very common disease being the most common cancer in human. As the mortality due to PTC is relatively low, understanding pathophysiology of the disease and risk prediction in individual patient have particular importance for optimal management, but little has been known. I suggest a reason for such a commonality of PTC, and would like to describe my view on some aspects of PTC including unresolved issue on management based on our recent observations.

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Thyroid
Erratum: Figure Correction: Standardized Thyroid Cancer Mortality in Korea between 1985 and 2010
Yun Mi Choi, Tae Yong Kim, Eun Kyung Jang, Hyemi Kwon, Min Ji Jeon, Won Gu Kim, Young Kee Shong, Won Bae Kim
Endocrinol Metab. 2015;30(1):116-116.   Published online March 27, 2015
DOI: https://doi.org/10.3803/EnM.2015.30.1.116
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Thyroid
Standardized Thyroid Cancer Mortality in Korea between 1985 and 2010
Yun Mi Choi, Tae Yong Kim, Eun Kyung Jang, Hyemi Kwon, Min Ji Jeon, Won Gu Kim, Young Kee Shong, Won Bae Kim
Endocrinol Metab. 2014;29(4):530-535.   Published online December 29, 2014
DOI: https://doi.org/10.3803/EnM.2014.29.4.530
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  • 35 Citations
AbstractAbstract PDFPubReader   CrossRef-TDMCrossref - TDM
Background

The prevalence of thyroid cancer has increased very rapidly in Korea. However, there is no published report focusing on thyroid cancer mortality in Korea. In this study, we aimed to evaluate standardized thyroid cancer mortality using data from Statistics Korea (the Statistical Office of Korea).

Methods

Population and mortality data from 1985 to 2010 were obtained from Statistics Korea. Age-standardized rates of thyroid cancer mortality were calculated according to the standard population of Korea, as well as World Health Organization (WHO) standard population and International Cancer Survival Standard (ICSS) population weights.

Results

The crude thyroid cancer mortality rate increased from 0.1 to 0.7 per 100,000 between 1985 and 2010. The pattern was the same for both sexes. The age-standardized mortality rate (ASMR) for thyroid cancer for Korean resident registration population increased from 0.19 to 0.67 between 1985 and 2000. However, it decreased slightly, from 0.67 to 0.55, between 2000 and 2010. When mortality was adjusted using the WHO standard population and ICSS population weights, the ASMR similarly increased until 2000, and then decreased between 2000 and 2010.

Conclusion

Thyroid cancer mortality increased until 2000 in Korea. It started to decrease from 2000.

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Thyroid
Solitary Skin Metastasis of Papillary Thyroid Carcinoma
Hyemi Kwon, Hyojung Kim, Sojung Park, Dong Eun Song, Won Gu Kim, Tae Yong Kim, Young Kee Shong, Won Bae Kim
Endocrinol Metab. 2014;29(4):579-583.   Published online December 29, 2014
DOI: https://doi.org/10.3803/EnM.2014.29.4.579
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AbstractAbstract PDFPubReader   CrossRef-TDMCrossref - TDM

A solitary skin metastasis is a rare manifestation of papillary thyroid carcinoma (PTC). A 55-year-old woman presented with a movable subcutaneous nodule in her anterior neck for several months. Three years ago, she underwent total thyroidectomy and remnant ablation for classical PTC (pT3N0M0) and was under thyroxine suppression therapy without any evidence of recurrent disease. The subcutaneous nodule was 0.4 cm in size, firm, and movable without any change in the overlying skin. Recurrent PTC was confirmed after excision biopsy. Eight months after, she got a new nodule along the previous excision site. After punch biopsy, metastatic PTC was confirmed in the deep dermis and was re-excised with a clear resection margin. This is the first report of a case of solitary skin metastasis of PTC in Korea. Although solitary skin metastasis of PTC is rare, it should be considered in patients with a skin nodule.

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Thyroid
Current Status and Future Perspectives in Differentiated Thyroid Cancer
Tae Yong Kim, Won Gu Kim, Won Bae Kim, Young Kee Shong
Endocrinol Metab. 2014;29(3):217-225.   Published online September 25, 2014
DOI: https://doi.org/10.3803/EnM.2014.29.3.217
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AbstractAbstract PDFPubReader   CrossRef-TDMCrossref - TDM

Thyroid cancer is increasing all over the world. The exact cause of this increase is still debated and there are conflicting reports. Sophisticated molecular studies suggest that environmental chemicals may have effects of thyroid carcinogenesis. The development of powerful molecular biology techniques has enabled targeted next-generation sequencing for detection of mutations in thyroid cancer, and this technique can make a specific diagnosis of thyroid cancer in cytologically indeterminate cases. The initial treatment of well-differentiated thyroid cancer (DTC) is surgery followed by radioiodine remnant ablation. However, further studies are needed to determine the optimal dosage of radioactive iodine for DTC patients with lateral neck metastasis. DTC is an indolent tumor and may cause death even decades later. Thus, long-term follow-up is mandatory. Recently, dynamic risk stratification (DRS) has begun to use stimulated thyroglobulin level at 1 year after the initial treatment and restratified the risk in accordance with the response to the initial treatment. This DRS strategy accurately predicts disease free survival and can be widely used in daily clinical settings. For the iodine refractory metastatic disease, redifferentiation therapy and targeted therapy are two promising alternative treatments. Sorafenib is the first approved agent for the treatment of progressive iodine refractory advanced thyroid cancer in Korea and may be very helpful for radioactive-refractory locally advanced or metastatic DTC. Selumetinib may be an effective redifferentiating agent and could be used within several years.

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Long-Term Survival of a Patient with Pulmonary Artery Intimal Sarcoma after Sequential Metastasectomies of the Thyroid and Adrenal Glands
Yun Mi Choi, Eun Kyung Jang, Seong Hee Ahn, Min Ji Jeon, Ji Min Han, Seong Chul Kim, Duck Jong Han, Gyungyup Gong, Tae Yong Kim, Young Kee Shong, Won Bae Kim
Endocrinol Metab. 2013;28(1):46-49.   Published online March 25, 2013
DOI: https://doi.org/10.3803/EnM.2013.28.1.46
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AbstractAbstract PDFPubReader   CrossRef-TDMCrossref - TDM

Cancer metastases to the thyroid or adrenal gland are uncommon. Furthermore, cases showing long-term survival after surgical resection of those metastatic tumors are rare. We report a case of pulmonary artery intimal sarcoma with metastases to the thyroid and adrenal glands sequentially that was successfully treated with sequential metastasectomies. A 62-year-old woman presented with a 4-week history of dyspnea on exertion and facial edema in November 1999. Echocardiography and chest computed tomography (CT) revealed an embolism-like mass in the pulmonary trunk. Pulmonary artery endarterectomy with pulmonary valve replacement was performed, and histopathology revealed pulmonary artery intimal sarcoma. A thyroid nodule was found by chest CT in November 2001 (2 years after initial surgery). During follow-up, this lesion showed no change, but we decided to obtain fine needle aspiration cytology (FNAC) in August 2004 (4.7 years after initial surgery). FNAC revealed atypical spindle cells suggestive of metastatic intimal sarcoma. She underwent total thyroidectomy. During follow-up, a right adrenal gland mass was detected by chest CT in March 2006 (6.3 years after initial surgery), and adrenalectomy was done, which also revealed metastatic sarcoma. She has been followed up without any evidence of recurrent disease until May 2012 (12.5 years after initial surgery).

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  • Pulmonary artery sarcoma: An important mimic of pulmonary embolism—Case reports and literature review
    Colin Tuft, Krishan Maheepala, Ajantha Raguparan, Anas Naeem, Suhrid Lodh, Steven Lindstrom
    Respirology Case Reports.2022;[Epub]     CrossRef
  • Rare case of metastatic liposarcoma to the thyroid gland and a review of the literature of metastatic sarcomas to the thyroid
    Monica H. Xing, Neil Mundi, Aparna Govindan, Azita Khorsandi, Margaret Brandwein‐Weber, Ammar Matloob, Bobby Liaw, Mark L. Urken
    Head & Neck.2021;[Epub]     CrossRef
  • Left pneumonectomy with pulmonary arterioplasty under cardiopulmonary bypass for pulmonary artery intimal sarcoma
    Akihiko Kitahara, Yuki Shimizu, Tatsuya Goto, Seijiro Sato, Terumoto Koike, Masanori Tsuchida
    The Journal of the Japanese Association for Chest Surgery.2018; 32(4): 492.     CrossRef
  • Intimal sarcoma of the pulmonary artery with multiple lung metastases: Long-term survival case
    Sonia García-Cabezas, Macarena Centeno-Haro, Simona Espejo-Pérez, Elvira Carmona-Asenjo, Alberto L Moreno-Vega, Rosa Ortega-Salas, Amalia Palacios-Eito
    World Journal of Clinical Oncology.2017; 8(4): 366.     CrossRef
  • Clinical Characteristics and Treatment Outcomes of Primary Pulmonary Artery Sarcoma in Korea
    Yunkyoung Lee, Hyun Jung Kim, Heeyoung Yoon, Chang-Min Choi, Yeon-Mok Oh, Sang-Do Lee, Chae-Man Lim, Woo-Sung Kim, Younsuck Koh, Jae Seung Lee
    Journal of Korean Medical Science.2016; 31(11): 1755.     CrossRef
  • An Extraordinary Case of Mesenchymal Chondrosarcoma Metastasis in the Thyroid
    Santiago Ortiz, Francisco Tortosa, Manuel Sobrinho Simões
    Endocrine Pathology.2015; 26(1): 33.     CrossRef
  • Presentation and management of pulmonary artery sarcoma
    Han Hsi Wong, Ioannis Gounaris, Ann McCormack, Marius Berman, Dochka Davidson, Gail Horan, Joanna Pepke-Zaba, David Jenkins, Helena M Earl, Helen M Hatcher
    Clinical Sarcoma Research.2015;[Epub]     CrossRef
  • Brief Review of Articles in 'Endocrinology and Metabolism' in 2013
    Won-Young Lee
    Endocrinology and Metabolism.2014; 29(3): 251.     CrossRef
Four Cases of Malignant Pleural Effusion in Patients with Papillary Thyroid Carcinoma.
Min Ji Jeon, Ji Hye Yim, Eui Young Kim, Won Gu Kim, Tae Yong Kim, Won Bae Kim, Young Kee Shong
Endocrinol Metab. 2011;26(4):330-334.   Published online December 1, 2011
DOI: https://doi.org/10.3803/EnM.2011.26.4.330
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  • 3 Citations
AbstractAbstract PDF
Papillary thyroid carcinoma could be a rare cause of malignant pleural effusion. The development of malignant pleural effusion in patients with papillary thyroid cancer is an extremely adverse prognostic indicator. Here, we report four cases that showed development of malignant pleural effusion during the clinical course of the papillary thyroid carcinoma and consider the prognosis. In four patients, the median survival time after the development of malignant pleural effusion was only 17 months.

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  • Pleural fluid due to papillary thyroid cancer
    Tomohiro Tamura, Toshihiro Shiozawa, Hiroaki Satoh, Koichi Kurishima, Katsunori Kagohashi, Norio Takayashiki, Nobuyuki Hizawa
    Oncology Letters.2019;[Epub]     CrossRef
  • Outcome and characteristics of patients with malignant pleural effusion from differentiated thyroid carcinoma
    Chisato Tomoda, Yuna Ogimi, Fumi Saito, Chie Masaki, Junko Akaishi, Kenichi Matsuzu, Akifumi Suzuki, Takashi Uruno, Keiko Ohkuwa, Hiroshi Shibuya, Wataru Kitagawa, Mitsuji Nagahama, Kiminori Sugino, Koichi Ito
    Endocrine Journal.2016; 63(3): 257.     CrossRef
  • A distinctive colour associated with high iodine content in malignant pleural effusion from metastatic papillary thyroid cancer: a case report
    Andrew Rosenstengel, Ee Mun Lim, Michael Millward, YC Gary Lee
    Journal of Medical Case Reports.2013;[Epub]     CrossRef
Response: Postoperative Findings of the Cytological Diagnosis of Follicular Neoplasm or Hurthle Cell Neoplasm and the Risk of Malignancy.
Ji Hye Yim, Won Bae Kim
Endocrinol Metab. 2011;26(3):277-278.   Published online September 1, 2011
DOI: https://doi.org/10.3803/EnM.2011.26.3.277
  • 20,845 View
  • 18 Download
AbstractAbstract PDF
No abstract available.
Comparison of Different Staging Systems for Predicting Recurrence of Papillary Thyroid Carcinoma.
Won Gu Kim, Eui Young Kim, Ji Hye Yim, Ji Min Han, Min Ji Jeon, Tae Yong Kim, Jin Sook Ryu, Gyungyub Gong, Suck Joon Hong, Won Bae Kim, Young Kee Shong
Endocrinol Metab. 2011;26(1):53-61.   Published online March 1, 2011
DOI: https://doi.org/10.3803/EnM.2011.26.1.53
  • 1,777 View
  • 19 Download
  • 10 Citations
AbstractAbstract PDF
BACKGROUND
Various staging systems for thyroid cancer that focus on cancer specific death have been suggested, but this approach had a limitation due to the relatively long clinical course and very low rate of cancer death. This study was performed to evaluate the staging systems and to determine the most predictive staging system for predicting recurrence. METHODS: The patients who underwent first total or near total thyroidectomy due to papillary thyroid cancer (PTC) at Asan Medical Center between January 1995 and December 2001 were the subjects of this study. The commonly used 8 staging systems were applied to these subjects. Disease free survival (DFS) and the relative importance of each staging system were determined by the Kaplan-Meier method, the Cox-proportional hazards model and the proportion of variation in the survival time explained (PVE). RESULTS: A total of 952 patients (M = 117, F = 835) were enrolled and their mean age was 45 years. During a median of 10 years of follow-up, 146 (15.3%) of 952 patients had recurred tumor. The independent prognostic factors were male gender, tumor size, extrathyroidal invasion and cervical lymph node metastasis. Risk stratification according to the American thyroid association (ATA) guideline was the most predictive staging system for recurrence of PTC (PVE 88.6%). The staging systems from EORTC (PVE 79.5%), and MACIS (PVE 68.4%) had significant values for predicting recurrence of PTC. The stage of NTCTCS could not predict recurrence (PVE 4.5%, P = 0.11). CONCLUSION: Risk stratification according to the ATA was most predictive staging system for predicting recurrence of PTC. The MACIS and EORTC staging systems have good value for predicting recurrence of PTC.

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  • Unmet Clinical Needs in the Treatment of Patients with Thyroid Cancer
    Won Bae Kim, Min Ji Jeon, Won Gu Kim, Tae Yong Kim, Young Kee Shong
    Endocrinology and Metabolism.2020; 35(1): 14.     CrossRef
  • Impact of delayed radioiodine therapy in intermediate‐/high‐risk papillary thyroid carcinoma
    Mijin Kim, Minkyu Han, Min Ji Jeon, Won Gu Kim, In Joo Kim, Jin‐Sook Ryu, Won Bae Kim, Young Kee Shong, Tae Yong Kim, Bo Hyun Kim
    Clinical Endocrinology.2019; 91(3): 449.     CrossRef
  • Clinical Value of Lymph Node Ratio Integration with the 8th Edition of the UICC TNM Classification and 2015 ATA Risk Stratification Systems for Recurrence Prediction in Papillary Thyroid Cancer
    Jandee Lee, Seul Gi Lee, Kwangsoon Kim, Seung Hyuk Yim, Haengrang Ryu, Cho Rok Lee, Sang Wook Kang, Jong Ju Jeong, Kee-Hyun Nam, Woong Youn Chung, Young Suk Jo
    Scientific Reports.2019;[Epub]     CrossRef
  • Clinical prognostic significance of cancer stem cell markers in patients with papillary thyroid carcinoma
    Yoon‑Jong Ryu, Ji‑Young Choe, Kyoungyul Lee, Soon‑Hyun Ahn
    Oncology Letters.2019;[Epub]     CrossRef
  • Dynamic Risk Stratification for Predicting Recurrence in Patients with Differentiated Thyroid Cancer Treated Without Radioactive Iodine Remnant Ablation Therapy
    Suyeon Park, Won Gu Kim, Eyun Song, Hye-Seon Oh, Mijin Kim, Hyemi Kwon, Min Ji Jeon, Tae Yong Kim, Young Kee Shong, Won Bae Kim
    Thyroid.2017; 27(4): 524.     CrossRef
  • Optimal cut-off age in the TNM Staging system of differentiated thyroid cancer: is 55 years better than 45 years?
    Mijin Kim, Young Nam Kim, Won Gu Kim, Suyeon Park, Hyemi Kwon, Min Ji Jeon, Hyeon Seon Ahn, Sin-Ho Jung, Sun Wook Kim, Won Bae Kim, Jae Hoon Chung, Young Kee Shong, Tae Hyuk Kim, Tae Yong Kim
    Clinical Endocrinology.2017; 86(3): 438.     CrossRef
  • Sub-Classification of Lateral Cervical Lymph Node Metastasis in Papillary Thyroid Carcinoma by Pathologic Criteria
    Min Ji Jeon, Won Gu Kim, Eun Kyung Jang, Yun Mi Choi, Dong Eun Song, Tae-Yon Sung, Jong Ho Yoon, Ki-Wook Chung, Suck Joon Hong, Jin-Sook Ryu, Ji Min Han, Tae Yong Kim, Young Kee Shong, Won Bae Kim, Konradin Metze
    PLOS ONE.2015; 10(7): e0133625.     CrossRef
  • Recent Changes in the Clinical Outcome of Papillary Thyroid Carcinoma With Cervical Lymph Node Metastasis
    Min Ji Jeon, Won Gu Kim, Yun Mi Choi, Hyemi Kwon, Dong Eun Song, Yu-Mi Lee, Tae-Yon Sung, Jong Ho Yoon, Suck Joon Hong, Jung Hwan Baek, Jeong Hyun Lee, Jin-Sook Ryu, Tae Yong Kim, Young Kee Shong, Ki-Wook Chung, Won Bae Kim
    The Journal of Clinical Endocrinology & Metabolism.2015; 100(9): 3470.     CrossRef
  • Differentiating the location of cervical lymph node metastasis is very useful for estimating the risk of distant metastases in papillary thyroid carcinoma
    Min Ji Jeon, Tae Yong Kim, Won Gu Kim, Ji Min Han, Eun Kyung Jang, Yun Mi Choi, Dong Eun Song, Jong Ho Yoon, Ki-Wook Chung, Suck Joon Hong, Young Kee Shong, Won Bae Kim
    Clinical Endocrinology.2014; 81(4): 593.     CrossRef
  • Influences of Hashimoto's Thyroiditis as Prognostic Factor of Papillary Thyroid Carcinoma
    Hyun Ju Park, Dong Kun Lee, Ji Won Seo, Myung Koo Kang, Heon Soo Park, Rock Bum Kim, Sung Hwan Suh, Mi Kyoung Park, Duk Kyu Kim, Jong Chul Hong
    Korean Journal of Otorhinolaryngology-Head and Neck Surgery.2014; 57(5): 320.     CrossRef
Postoperative Findings of the Cytological Diagnosis of Follicular Neoplasm or Hurthle Cell Neoplasm and the Risk of Malignancy.
Ji Hye Yim, Eui Young Kim, Won Gu Kim, Tae Yong Kim, Gyungyup Gong, Suck Joon Hong, Won Bae Kim, Young Kee Shong
Endocrinol Metab. 2010;25(4):316-320.   Published online December 1, 2010
DOI: https://doi.org/10.3803/EnM.2010.25.4.316
  • 1,699 View
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  • 4 Citations
AbstractAbstract PDF
BACKGROUND
Follicular neoplasm (FN) or Hurthle cell neoplasm (HN) is a less well understood pitfall when evaluating thyroid nodule with fine-needle aspiration (FNA). This study aimed to determine the rates of malignancy and the predictive factors for malignancy in thyroid nodules with a cytological diagnosis of FN or HN. METHODS: The patients who were cytologically diagnosed as having FN or HN after FNA between 1995 and 2004 at Asan Medical Center were included in this study. We collected the pathology data until 2009 and we analyzed the clinical characteristics associated with malignancy. RESULTS: A total 478 patients were cytologically diagnosed as having FN or HN during the study period and 327 (68%) among them underwent thyroid surgery. Thyroid malignancy was confirmed in 157 (48%) of 327 patients. Malignancy was confirmed in 124 patients with FN (124/253, 49%). They were 48 papillary, 65 follicular, 7 Hurthle cell and 3 medullary carcinomas and 1 anaplastic carcinoma. The malignancy in the cases of HN (33/71, 44.6%) was 9 papillary, 4 follicular and 20 Hurthle cell carcinomas. The risk of malignancy was not associated with male gender, a larger tumor size (> 4 cm) or the diagnosis of HN. However, an age below 20 years (RR 3.6, P = 0.03) and above 60 years (RR 2.3, P = 0.04) was associated with an increased risk of malignancy. CONCLUSION: About half of the patients with FN or HN on FNA cytology were diagnosed as having thyroid cancer after surgery. The malignancy rate for the cytologic diagnosis of HN was similar to that for FN. Thyroid surgery should be recommended for this situation, and especially for patients younger than 20 years or older than 60 years.

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  • Diagnostic Value of Preoperative Serum Thyroglobulin Measurement for the Diagnosis of Malignancy in Follicular or Hürthle Cell Neoplasms of the Thyroid Gland
    Nam Kyu Kim, Seong Joo Kang, Weon Hyoung Lee, Go Eun Yeo, You Jin Han, Bu Kyung Kim, Su Kyoung Kwon, Yo-Han Park, Young Sik Choi
    Kosin Medical Journal.2014; 29(1): 17.     CrossRef
  • Fine Needle Aspiration Cytology of Thyroid Follicular Neoplasm: Cytohistologic Correlation and Accuracy
    Changyoung Yoo, Hyun Joo Choi, Soyoung Im, Ji Han Jung, Kiouk Min, Chang Suk Kang, Young-Jin Suh
    Korean Journal of Pathology.2013; 47(1): 61.     CrossRef
  • Predictive Factors of Malignancy in Thyroid Nodules with a Cytological Diagnosis of Follicular Neoplasm
    Seong Hyeon Lee, Jeong Su Baek, Joo Young Lee, Jung Ah Lim, Soo Youn Cho, Tae Hyun Lee, Yun Hyi Ku, Hong Il Kim, Min Joo Kim
    Endocrine Pathology.2013; 24(4): 177.     CrossRef
  • Postoperative Findings of the Cytological Diagnosis of Follicular Neoplasm or Hürthle Cell Neoplasm and Risk of Malignancy
    Jung Uee Lee, Minho Shong
    Endocrinology and Metabolism.2010; 25(4): 298.     CrossRef
Response: Effects of alpha-lipoic Acid on Differentiation of Thyroid Cancer Cells.
Won Gu Kim, Won Bae Kim
Endocrinol Metab. 2010;25(3):246-247.   Published online September 1, 2010
DOI: https://doi.org/10.3803/EnM.2010.25.3.246
  • 1,207 View
  • 18 Download
AbstractAbstract PDF
No abstract available.
Factors Influencing Peripheral Conversion of Thyroxine to Tri-Iodothyronine in Athyreotic Individuals during Levothyroxine Replacement.
Eui Young Kim, Won Gu Kim, Tae Yong Kim, Jong Ho Yoon, Suck Joon Hong, Young Kee Shong, Won Bae Kim
Endocrinol Metab. 2010;25(2):119-124.   Published online June 1, 2010
DOI: https://doi.org/10.3803/EnM.2010.25.2.119
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AbstractAbstract PDF
BACKGROUND
Tri-iodothyronine (T3) is the main active hormone, and 20% of this is derived from the thyroid gland and 80% is from the peripheral tissue according to 5'-monodeiodination of thyroxine (T4). In the previous studies, normal T3 levels were achieved with traditional levothyroxine (LT4) therapy alone in athyreotic patients, but there has been no data about the factors influencing peripheral conversion of LT4. The aim of this study was to determine the factor(s) influencing peripheral conversion of LT4 to T3 in athyreotic patients during LT4 replacement. METHODS: The patients who underwent total-thyroidectomy for any cause, and mostly for thyroid cancers, at Asan Medical Center between 2000 and 2008 were enrolled. The free T4, T3 and thyroid stimulating hormone (TSH) levels and age, gender, weight, height, body mass index (BMI) and the T4 dose were measured. Only patients with normal ranges of free T4 and TSH were included in the analysis. RESULTS: A total of 143 patients were enrolled. The mean T3, free T4 and TSH levels were 143.7 ng/dL, 1.4 ng/dL and 1.6 microU/mL, respectively. The mean weight and BMI were 62.9 kg and 24.6 kg/m2, respectively. We divided them into two groups according to the serum T3 level and we compared the characteristics of the groups. There were no differences in age, the gender distribution, the T4 dose/weight and the BMI between the low T3 group (T3 < or = 122 ng/dL, n = 14) and the normal T3 group (T3 > 122 ng/dL, n = 129). In the low T3 group, the mean body weight was significantly lower than that of the normal T3 group (59.0 +/- 6.0 vs. 63.4 +/- 9.9, respectively, P = 0.025). CONCLUSION: Lean body mass seems to be an important factor for determining the peripheral conversion of T4 to T3 in human. This suggest that a combination of T3/T4 is better than T4 only when we treat the patients with hypothyroidism and who have a negligible amount of functioning thyroid tissue, if they have a low lean body mass.
Effects of alpha-lipoic Acid on Differentiation of Thyroid Cancer Cells.
Won Gu Kim, Doo Hee Han, Hyun Jeung Choi, Eui Young Kim, Tae Yong Kim, Young Kee Shong, Won Bae Kim
J Korean Endocr Soc. 2010;25(1):28-36.   Published online March 1, 2010
DOI: https://doi.org/10.3803/jkes.2010.25.1.28
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AbstractAbstract PDF
BACKGROUND
Induction of re-differentiation is necessary for the proper treatment of patients with recurrent or metastatic differentiated thyroid cancer (DTC) because cancer cells show de-differentiation in about 30% of these patients. In this study, we evaluated the expression of thyroid specific genes after treatment with various agents to induce re-differentiation in the follicular thyroid cancer cell line FTC-133. METHODS: FTC-133 cells were treated with U0126, LY294002, trichostatin A, retinoic acid (RA), 5'-azacytidine and alpha-lipoic acid (ALA). We evaluated mRNA expression of thyroid specific genes, thyroglobulin (Tg), sodium iodine symporter (NIS), PAX-8 and TTF-1 by reverse transcriptase polymerase chain reaction (PCR). Quantified expression of Tg mRNA was also evaluated by real-time PCR. RESULTS: The expression of Tg mRNA increased after 48 h of treatment with 0.1 uM RA and the expression of Tg mRNA and TTF-1 mRNA increased after 48-72 h of treatment with ALA (10~100 uM). There was no change in thyroid specific gene expression by the other agents. Increased expression of Tg mRNA was confirmed by real-time PCR (1.3 times by 10 uM ALA and 3.6 times by 100 uM ALA). There was no basal NIS mRNA expression in FTC-133 cells and none of the tested agents induced expression of NIS mRNA. There was no change in phosphorylation of AMPK1-alpha after ALA treatment of FTC-133 cells. CONCLUSION: ALA increases mRNA expression of Tg and TTF-1 of FTC-133 thyroid cancer cells and these effects are not mediated by activation of AMP kinase. The finding that ALA could be a potential re-differentiation inducing agent in thyroid cancer cells is novel. Further studies are needed to elucidate the mechanism of induction of re-differentiation. Furthermore, the effect of ALA on NIS expression and on iodine uptake should be evaluated using diverse thyroid cancer cell lines.
Effects of Peroxisome Proliferator-Activated Receptor (PPAR) Delta on the Growth and Invasion of a Thyroid Cancer Cell Line.
Won Gu Kim, Hyun Jeung Choi, Eui Young Kim, Tae Yong Kim, Won Bae Kim, Seong Chul Kim, Young Kee Shong
J Korean Endocr Soc. 2009;24(1):25-32.   Published online March 1, 2009
DOI: https://doi.org/10.3803/jkes.2009.24.1.25
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AbstractAbstract PDF
BACKGROUND
Peroxisome proliferator-activated receptor delta (PPAR-delta) is a ligand-activated nuclear transcription factor that is associated with many diseases, such as diabetes, obesity, metabolic syndrome, and cancer. However, the function of PPAR-delta is controversial in carcinogenesis since its ligands may inhibit or promote the growth of cancer cells. The purpose of this study was to determine the effect of GW501516, the specific agonist of PPAR-delta, in the growth and invasiveness of thyroid cancer cell lines by modulation of the target genes, ANGPTL-4 and MCP-1. METHODS: Three kinds of human cancer cell lines, FRO (thyroid anaplastic carcinoma), NPA (melanoma), and ARO (colon cancer) were treated with GW501516 in serum-free media. Cell viability was assayed using a colorimetric cell counting kit-8 assay. The changes in the level of expression of PPAR-delta and its target genes, angiopoietin-like protein-4 (ANGPTL-4) and monocyte chemotactic protein-1 (MCP-1), were determined by RT-PCR analysis and invasiveness was assessed by a cell invasion assay kit. RESULTS: GW501516 inhibited the cell growth of cancer cell lines in a dose-dependent manner and modulated the stimulation of ANGPTL-4, as well as inhibition of MCP-1. These effects were more prominent in NPA and ARO, but less effective in the thyroid cancer cell line, which had higher PPAR-delta and lower ANGPTL-4 mRNA levels. The inhibitory effects of GW501516 on cancer invasiveness had a similar pattern. CONCLUSION: The activation of PPAR-delta by GW501516 reduced the cell growth and invasiveness of the thyroid cancer cell line. This effect of GW501516 was associated with a stimulatory effect of ANGPTL4 and an inhibitory effect of MCP-1 in cancer cell lines. GW501516 was less effective in the thyroid cancer cell line, which had a low basal ANGPTL-4 mRNA level. The findings of our study serve as an impetus for further studies to elucidate the precise role of ANGPTL-4 and PPAR-delta in carcinogenesis.
A Case of Painful Graves' Disease.
Ji Yun Jeong, Tae Yong Kim, Eun Hee Kim, Eui Young Kim, Sang Ah Lee, Ji Hye Yim, Kyung Min Kim, Won Bae Kim, Young Kee Shong
J Korean Endocr Soc. 2008;23(5):337-341.   Published online October 1, 2008
DOI: https://doi.org/10.3803/jkes.2008.23.5.337
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AbstractAbstract PDF
Graves' disease rarely presents as pain and tenderness of goiter, with only a few cases reported in the literature. We describe a case of painful Graves' disease presenting as 2 episodes of painful goiter.
A Case of Carcinoma Showing Thymus-Like Differentiation (CASTLE) in the Thyroid.
Eun Hee Kim, Ji Yun Jeong, Eui Young Kim, Sang Ah Lee, Kyung Min Kim, Ji Hye Yim, Won Gu Kim, Tae Yong Kim, Sun A Kim, Gyungyup Gong, Young Kee Shong, Won Bae Kim
J Korean Endocr Soc. 2008;23(4):272-276.   Published online August 1, 2008
DOI: https://doi.org/10.3803/jkes.2008.23.4.272
  • 1,337 View
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  • 2 Citations
AbstractAbstract PDF
Carcinoma Showing Thymus-Like Differentiation (CASTLE) is a very rare malignant neoplasm of the thyroid, and this resembles lymphoepithelioma or squamous cell carcinoma of the thymus. It originates from ectopic thymic tissue or remnants of the branchial pouches. We recently experienced a case of CASTLE in the thyroid gland of a 61-year-old woman. She presented with an asymptomatic mass in the right thyroid gland and she was diagnosed with 'poorly differentiated carcinoma' of the thyroid by fine needle aspiration cytology (FNAC). Total thyroidectomy was performed for both diagnostic and therapeutic purposes. Histologic examination of the resected tumor showed that the tumor was lobulated with expanding fibrous bands, and it was infiltrated by lymphocytes and plasma cells. The tumor cells had oval, large vesicular nuclei and prominent nucleoli, and the immunohistochemical staining was positive for CD5 and bcl-2, so the patient was diagnosed with thyroid CASTLE. We report here on a case of CASTLE in the thyroid gland treated by surgery and external neck radiation therapy.

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  • Intrathyroidal thymic carcinoma exhibiting neuroendocrine differentiation: Case report with cytomorphology, immunocytochemistry, and review of the literature focusing on cytology
    Wen‐hao Ren, Kun Dong, Xiao‐zheng Huang, Yan‐li Zhu
    Diagnostic Cytopathology.2019; 47(11): 1197.     CrossRef
  • Cytologic Findings of Thyroid Carcinoma Showing Thymus-like Differentiation: A Case Report
    Sunhee Chang, Mee Joo, Hanseong Kim
    Korean Journal of Pathology.2012; 46(3): 302.     CrossRef
Effects of Simvastatin on the Growth and Invasion of Anaplastic Thyroid Cancer Cells Lines.
Hyun Jeung Choi, Tae Yong Kim, Eui Young Kim, Won Gu Kim, Won Bae Kim, Young Kee Shong
J Korean Endocr Soc. 2008;23(4):238-244.   Published online August 1, 2008
DOI: https://doi.org/10.3803/jkes.2008.23.4.238
  • 1,516 View
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  • 1 Citations
AbstractAbstract PDF
BACKGROUND
Anaplastic thyroid carcinoma has grave prognosis with most patient dying within 6 months of diagnosis. 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors have been reported to have an anticancer effect in experimental and clinical studies. In this study, we investigated the effect of HMG-CoA reductase inhibitors on cell growth, invasiveness, adherence and signal transduction to evaluate the possibility of simvastatin as an agent for treatment of thyroid cancer. METHODS: The viability of simvastatin treated 3 thyroid cancer cell lines (FRO, WRO, and ARO) were determined. We evaluated the cell migration, anchorage-independent growth and invasion ability in anaplastic thyroid cell line. The expression and phosphorylation of focal adhesion kinase (FAK) and extracellular signal-regurated kinase (ERK) were determined by immunoblot analysis. RESULTS: Three thyroid cancer cell lines showed concentration dependent decrease of viability after treatment with 100~200 mM of simvastatin. Anaplastic ARO cell line showed the most predominant decrease in viability. In ARO cell lines, cell migration was decreased by concentration dependent manner after treatment with simvastatin (concentration > or = 5 mM). Anchorage independent colony formation also decreased after simvastatin (> or = 10 mM). Finally, immunoblot analysis revealed that the phosphorylation status of FAK and ERK decreased in time dependent manner following treatment with 10 mM of simvastatin. CONCLUSION: The results of this study suggest that simvstatin exerts a favorable effect on the progression and metastasis of thyroid cancer. However, further studies are needed to elucidate the related mechanisms and signal transductions prior to its therapeutic application.

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  • The Effect of Atorvastatin and Simvastatin on NIS Expression of the TPC-1 Cell under the Therapeutic Blood Concentrations
    Tae Kyoon Kim, Hye Sook Jung, Chang Shin Yoon, Jung Hae Ko, Hae Jung Jun, Min Jung Kwon, Sun Hee Lee, Mi Kyung Kim, Jeong Hyun Park
    Endocrinology and Metabolism.2010; 25(3): 192.     CrossRef
A Case of Diffuse Hemorrhage into the Thyroid Gland after Fine Needle Aspiration, and This was Treated by Arterial Embolization.
Eui Young Kim, Jung Min Kim, Eun Hee Kim, Ji Yun Jeong, Sang Ah Lee, Ji Young Choi, Ji Hye Yim, Pil Hyung Lee, Tae Yong Kim, Young Kee Shong, Won Bae Kim
J Korean Endocr Soc. 2008;23(3):199-203.   Published online June 1, 2008
DOI: https://doi.org/10.3803/jkes.2008.23.3.199
  • 1,554 View
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  • 1 Citations
AbstractAbstract PDF
Although hematoma formation after fine needle aspiration cytology fine needle aspiration cytology (FNAC) is a most common complication and most of these hematomas are self-limiting with minimal pain, a massive intra-thyroidal hemorrhage that produces acute airway obstruction had rarely been reported on.

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  • Endovascular treatment of massive hemorrhage arising from inferior thyroid artery after fine needle aspiration of thyroid: a case report
    Ho Sig Jang, Yook Kim
    BMC Surgery.2021;[Epub]     CrossRef
Clinical Applications of Thyrotropin Binding Inhibitor Immunoglobulin (TBII) Assays.
Won Bae Kim
J Korean Endocr Soc. 2008;23(3):174-178.   Published online June 1, 2008
DOI: https://doi.org/10.3803/jkes.2008.23.3.174
  • 1,402 View
  • 18 Download
  • 3 Citations
AbstractAbstract PDF
No abstract available.

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  • Medical Treatment of Graves' Disease
    Hyun-Kyung Chung
    International Journal of Thyroidology.2019; 12(2): 79.     CrossRef
  • When should antithyroid drug therapy to reduce the relapse rate of hyperthyroidism in Graves’ disease be discontinued?
    Suyeon Park, Eyun Song, Hye-Seon Oh, Mijin Kim, Min Ji Jeon, Won Gu Kim, Tae Yong Kim, Young Kee Shong, Doo Man Kim, Won Bae Kim
    Endocrine.2019; 65(2): 348.     CrossRef
  • Usefulness of Measuring Thyroid Stimulating Antibody at the Time of Antithyroid Drug Withdrawal for Predicting Relapse of Graves Disease
    Hyemi Kwon, Won Gu Kim, Eun Kyung Jang, Mijin Kim, Suyeon Park, Min Ji Jeon, Tae Yong Kim, Jin-Sook Ryu, Young Kee Shong, Won Bae Kim
    Endocrinology and Metabolism.2016; 31(2): 300.     CrossRef
Association between Cigarette Smoking and Thyroid Function in Adults without Previous History of Thyroid Disease.
Bo Hyun Kim, Won Bae Kim, Tae Yong Kim, Hong Kyu Kim, Seong Hoon Jeon, Chang Won Lee, Young Kee Shong
J Korean Endocr Soc. 2008;23(2):123-128.   Published online April 1, 2008
DOI: https://doi.org/10.3803/jkes.2008.23.2.123
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AbstractAbstract PDF
BACKGROUND
Cigarette smoking has a significant impact on thyroid function. However, the association between smoking and thyroid function is incompletely understood. METHODS: We conducted a cross-sectional study that included 90,970 adults (age range: 20 to 79) who had visited the health promotion center at Asan Medical Center between January 1, 2001, and December 31, 2003. Those subjects with previous known thyroid disease, a history of thyroid operation, a history of thyroid function altering medication (herb, estrogen or digestive) or a family history of thyroid disease were excluded. Finally, 47,577 subjects (males: 30,726, females: 16,851) were included in this study. We calculated the age-adjusted geometric mean of the serum TSH and the age-adjusted mean of the serum free T4 among the current, former and never smokers. We also analyzed the age-adjusted prevalence of hypothyroidism and hyperthyroidism among each group. RESULTS: Among men, the geometric mean TSH level was significantly low in the current (1.40 mIU/L, 95% confidence interval [CI]: 1.38-1.41) and former smokers (1.59 mIU/L, 95% CI: 1.57-1.61) compared with the never smokers (1.65 mIU/L, 95% CI: 1.63-1.68). The mean free T4 level was high in the current smokers (1.236 ng/dL, 95% CI: 1.234-1.239) compared with the never smokers (1.234 ng/dL, 95% CI: 1.230-1.238). Similarly, among women, the geometric mean TSH level was low in the current smokers (1.75 mIU/L, 95% CI: 1.67-1.87) compared with the never smokers (1.85 mIU/L, 95% CI: 1.83-1.87). The mean free T4 level was high in the current smokers (1.149 ng/dL, 95% CI: 1.139-1.159) compared with the never smokers (1.138 ng/dL, 95% CI: 1.135-1.140). Among the current male smokers, heavy daily smoking (over 2 packs per day) was more associated with low TSH levels than moderate smoking (less than 1 pack per day). In men, the prevalence of subclinical hypothyroidism was low in the current smokers compared with the never smokers (odds ratio: 0.53, 95% CI: 0.43-0.66). CONCLUSION: We found that current smokers had lower TSH levels and higher free T4 levels than never smokers in both men and women and smoking was associated with a low prevalence of subclinical hypothyroidism in men, which may be of importance when evaluating subjects with subclinical hypothyroidism in Korea.

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  • Reference interval for thyrotropin in a ultrasonography screened Korean population
    Mijin Kim, Tae Yong Kim, Soo Han Kim, Yunkyoung Lee, Su-yeon Park, Hyung-don Kim, Hyemi Kwon, Yun Mi Choi, Eun Kyung Jang, Min Ji Jeon, Won Gu Kim, Young Kee Shong, Won Bae Kim
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    Ji Eun Park, Ho Chan Cho
    Journal of Korean Thyroid Association.2012; 5(1): 52.     CrossRef
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    Joo Hyung Kim, Sol Ah Park, Nam Hoon Kim, Jae Hee Ahn, Yoon Jung Kim, Myongjin Cho, Yoon Jung Lee, Hye Jin Yoo, Hee Young Kim, Ji A Seo, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Dong Seop Choi, Sin Gon Kim
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CAG Repeats in the Androgen Receptor Polymorphism do not Correlate with Thyrotoxic Periodic Paralysis.
Won Gu Kim, Tae Yong Kim, Jung Min Kim, Yoon Soo Rhee, Hyun Jeung Choi, Won Bae Kim, Young Kee Shong
J Korean Endocr Soc. 2008;23(2):117-122.   Published online April 1, 2008
DOI: https://doi.org/10.3803/jkes.2008.23.2.117
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  • 3 Citations
AbstractAbstract PDF
BACKGROUND
Thyrotoxic periodic paralysis (TPP) occurs mostly in males, but no studies have addressed the role of androgen in the disease. Hyperinsulinemia can precipitate acute paralysis in TPP patients. CAG repeats in the androgen receptor (AR), an X-linked gene, correlate with serum insulin levels. AIM: To evaluate whether CAG repeats in the AR gene might predict the susceptibility to TPP in Korean male Graves' patients. METHODS: We evaluated CAG repeat length in a series of 33 male TPP patients and 48 control patients by direct sequencing of the PCR product of the AR promoter site. Control patients were male Graves' patients without a history of paralysis. RESULTS: The CAG repeat length varied from 15 to 34 (median of 23). The upper quartile of CAG length was equal to or above 26 repeats (long AR). The distribution of long AR was 0.30 in TPP and 0.15 in control patients, respectively (odds ratio, 2.51; 95% confidence interval, 0.92~6.85; P = 0.09). CONCLUSION: AR gene polymorphisms may not confer genetic susceptibility to TPP in Korean male patients with Graves' disease.

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  • Contributions of CAG repeat length in the androgen receptor gene and androgen profiles to premature pubarche in Korean girls
    Min Jae Kang, Jeong Seon Lee, Hwa Young Kim, Hae Woon Jung, Young Ah Lee, Sun Hee Lee, Ji-Young Seo, Jae Hyun Kim, Hye Rim Chung, Se Young Kim, Choong Ho Shin, Sei Won Yang
    Endocrine Journal.2017; 64(1): 91.     CrossRef
  • Thyrotoxic Periodic Paralysis and Polymorphisms of the ADRB2, AR, and GABRA3 Genes in Men with Graves Disease
    Suyeon Park, Tae Yong Kim, Soyoung Sim, Seonhee Lim, Mijin Kim, Hyemi Kwon, Min Ji Jeon, Won Gu Kim, Young Kee Shong, Won Bae Kim
    Endocrinology and Metabolism.2016; 31(1): 142.     CrossRef
  • Androgen Receptor Gene CAG Repeat Polymorphism and Effect of Testosterone Therapy in Hypogonadal Men in Korea
    Min Joo Kim, Jin Taek Kim, Sun Wook Cho, Sang Wan Kim, Chan Soo Shin, Kyong Soo Park, Seong Yeon Kim
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Trends Analysis of Characteristics of Thyroid Cancer Patients in One Medical Center.
Seung Hun Lee, Tae Yong Kim, Jin Sook Ryu, Gyungyub Gong, Won Bae Kim, Seong Chul Kim, Suck Joon Hong, Young Kee Shong
J Korean Endocr Soc. 2008;23(1):35-43.   Published online February 1, 2008
DOI: https://doi.org/10.3803/jkes.2008.23.1.35
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AbstractAbstract PDF
BACKGROUND
The incidence of thyroid cancer is rapidly increasing. The aim of this study is to examine time trends in the characteristics of thyroid cancer and to determine the cause of the increase of thyroid cancer. METHODS: We evaluated 4,646 patients that underwent surgery at the Asan Medical Center for thyroid cancer between 1995 and 2006. Patients were evaluated concerning the histology, size of the primary tumor, sex, and age at the time of surgery. RESULTS: Surgically treated case of thyroid cancer increased from 91 in 1995 to 960 in 2006-a 10.5-fold increase during the 12-year period. Based on the histological categories, the proportion of papillary thyroid carcinomas (PTCs) increased from 79.1% to 94.5% during the 12-year period. According to the primary tumor size in the PTCs, the proportion of PTCs measuring 1 cm or smaller increased from 14% to 56% during the 12-year period. Whereas the proportion of PTCs measuring from 1 cm to 2 cm were similar (between 31% and 41% during the 12-year period), the proportion of PTC measuring from 2 cm to 4 cm decreased from 51% to 11% during the 12-year period. Thyroid cancer affected women more often than men by a ratio of 3.7. PTC was most common in patients in their forties, especially among women. CONCLUSIONS: The increasing number of surgically treated cases of thyroid cancer is predominantly due to an increase of papillary thyroid cancer measuring 1 cm or less. These trends suggest that the increase in surgically treated cases of thyroid cancer reflects increased detection of occult thyroid cancer due to advances in medical surveillance of impalpable nodules rather than a true increase in the number of thyroid cancers.

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    Hye Jeong Kim, Na Kyung Kim, Hyeong Kyu Park, Dong Won Byun, Kyoil Suh, Myung Hi Yoo, Yong-Ki Min, Sun Wook Kim, Jae Hoon Chung
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Retraction: Completion Thyroidectomy in Patient with Differentiated Thyroid Cancer Who Initially Underwent Ipsilateral Operation.
Eun Sook Kim, Jung Min Koh, Won Bae Kim, Suck Joon Hong, Young Kee Shong
J Korean Endocr Soc. 2007;22(6):480-480.   Published online December 1, 2007
DOI: https://doi.org/10.3803/jkes.2007.22.6.480
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PDF
Management Guidelines for Patients with Thyroid Nodules and Thyroid Cancer.
Won Bae Kim, Tae Yong Kim, Hyuk Sang Kwon, Won Jin Moon, Jae Bok Lee, Young Sik Choi, Seok Ki Kim, Sun Wook Kim, Ki wook Chung, Jung Hwan Baek, Byung Il Kim, Do Joon Park, Dong Gyu Na, Jun Ho Choe, Jae Hoon Chung, Hye Seung Jung, Jeong Han Kim, Kee Hyun Nam, Hang Seok Chang, Woong Youn Chung, Soon Won Hong, Suck Joon Hong, Jeong Hyun Lee, Ka Hee Yi, Young Suk Jo, Ho Cheol Kang, Minho Shong, Jin Woo Park, Jong Ho Yoon, Seong Joon Kang, Kwang Woo Lee
J Korean Endocr Soc. 2007;22(3):157-187.   Published online June 1, 2007
DOI: https://doi.org/10.3803/jkes.2007.22.3.157
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AbstractAbstract PDF
No abstract available.

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Effects of Wnt-1 on the Growth and Apoptosis of FRTL-5 Cells.
Jung Min Kim, Tae Yong Kim, Young Kee Shong, Yoon Soo Rhee, Eun Jung Park, Hyun Chung Choi, Won Bae Kim
J Korean Endocr Soc. 2007;22(1):35-44.   Published online February 1, 2007
DOI: https://doi.org/10.3803/jkes.2007.22.1.35
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AbstractAbstract PDF
BACKGROUND
Wnt proteins are major signaling molecules involved in embryonic induction, generation of cell polarity and the cell fate decision. A central player in the Wnt signaling pathways is beta-catenin. Several studies have suggested that the Wnt/beta-catenin signaling pathway may be involved in the physiologic/pathologic control of thyroid cell growth and function. METHODS: We investigated the effect of thyroid-stimulating hormone (TSH) on the expression of Wnt proteins in FRTL-5 cells. To evaluate the effect of Wnt-1 on FRTL-5 cells growth, we isolated a stable cell line that overexpressed Wnt-1 (W1), and a vector-transfected cell clone (V3) was used as a control. We investigated the differences in the cellular growth rate, the cell cycle and cell apoptosis in the W1 and V3 cell lines. RESULTS: TSH caused a significant increase in the Wnt-1 level and a pronounced decrease in both the active and total beta-catenin levels in the FRTL-5 cells. The growth rate, the percentage of cells in the S/G2/M phase and the c-myc level were significantly higher in the W1 cells compared with the V3 cells. There was no change in the beta-catenin level and the cyclin D1 level in the W1 cells compared with the V3 cells. The cellular apoptosis induced by actinomycin-D seemed to be significantly decreased because the level of bcl-2 was increased in the W1 cells compared with the V3 cells. CONCLUSION: The FRTL-5 cells expressed Wnt-1 protein, and TSH increased the Wnt-1 expression, and it paradoxically decreased beta-catenin in the FRTL-5 cells. Overexpression of Wnt-1 in the FRTL-5 cells increased cell growth and it decreased apoptosis. Growth stimulation by Wnt-1 overexpression was not mediated by beta-catenin (the canonical Wnt pathway), but seemed to be mediated by activation of the Wnt/Ca2+ pathway, which involves an increased c-myc level. Suppression of apoptosis with Wnt-1 overexpression was due to the increased bcl-2 level.
Retraction: Clinical Characteristics of Poorly Differentiated Carcinoma of the Thyroid and Comparison of Survival to Tall Cell and Columnar Cell Variants of the Papillary Carcinoma.
Tae Sik Jung, Jae Hoon Chung, Young Lyun Oh, Tae Yong Kim, Young Kee Shong, Won Bae Kim, Kyung Won Kim, Young Joo Park, Bo Youn Cho
J Korean Endocr Soc. 2006;21(6):589-589.   Published online December 1, 2006
DOI: https://doi.org/10.3803/jkes.2006.21.6.589
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AbstractAbstract PDF
No abstract available.
Prevalence of Ultrasonographically-Detected Thyroid Nodules in Adults without Previous History of Thyroid Disease.
Ji Hye Suk, Tae Yong Kim, Mi Kyung Kim, Won Bae Kim, Hong Kyu Kim, Seong Hoon Jeon, Young Kee Shong
J Korean Endocr Soc. 2006;21(5):389-393.   Published online October 1, 2006
DOI: https://doi.org/10.3803/jkes.2006.21.5.389
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  • 11 Citations
AbstractAbstract PDF
BACKGROUND
The prevalence of palpable thyroid nodules in the general population is about 5%, and is 3~5 times higher in women than in men. However, much higher prevalence, up to 50%, was reported from autopsy data. Recently, the use of high resolution ultrasonography for routine check-up has resulted in much more detection of non-palpable thyroid nodules. We studied the prevalence of thyroid nodules in healthy adults without history of thyroid disease, and compared the prevalence in relation to palpability, age and gender. METHODS: The prevalence of thyroid nodules was studied in adults aged from 20 to 79 years who had visited the health promotion center at Asan Medical Center, Seoul, Korea, from Jan 2002 to Dec 2003. Subjects with previous thyroid disease were excluded. 7,440 subjects (6,168 female, 1,272 men) were included in this study. Thyroid palpation was performed and followed by ultrasonography using a 12-MHz real-time scanner. RESULTS: Thyroid nodules were detected in 3,040 of the 7,440 subjects (41%). Palpable nodules were present in 213 (3%), and non-palpable, but ultrasonographically detected thyroid nodules were present in 2,827 (38%). Thyroid nodules were present in 2,602 women (42.2%) and 370 men (29%). Among them, 159 women (2.6%) and 54 men (4.2%) had palpable thyroid nodules and 2,443 women (39.6%) and 316 men (24.8%) had non-palpable but ultrasonographically detected nodules. A significant linear trend was found between age and the prevalence of thyroid nodules. CONCLUSIONS: The prevalence of ultrasonographically detected thyroid nodules in adults with no previous history of thyroid disease was 41%. The prevalence of palpable nodules and non-palpable, but ultrasonographically detected nodules were 3% and 38%, respectively. Thyroid nodules were detected in 42.2% of women and 29% of men, showing that thyroid nodules are very common in healthy adults, even in men.

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    Hyemi Kwon, Jin-hyung Jung, Kyung-Do Han, Yong-Gyu Park, Jung-Hwan Cho, Da Young Lee, Ji Min Han, Se Eun Park, Eun-Jung Rhee, Won-Young Lee
    Endocrinology and Metabolism.2018; 33(2): 260.     CrossRef
  • An Iodine Database for Common Korean Foods and the Association between Iodine Intake and Thyroid Disease in Korean Adults
    Mi-Rhan Han, Dal Lae Ju, Young Joo Park, Hee-Young Paik, YoonJu Song
    International Journal of Thyroidology.2015; 8(2): 170.     CrossRef
  • Management of Thyroid Nodules and Cancers Arising in the Elderly
    Eunyoung Kim, June Young Choi, Kyu Eun Lee
    Journal of Korean Thyroid Association.2012; 5(2): 99.     CrossRef
  • Screening of Thyroid Cancer and Management of Thyroid Incidentaloma
    Jung Jin Cho
    Korean Journal of Family Medicine.2010; 31(2): 87.     CrossRef
  • Postoperative Findings of the Cytological Diagnosis of Follicular Neoplasm or Hürthle Cell Neoplasm and the Risk of Malignancy
    Ji Hye Yim, Eui Young Kim, Won Gu Kim, Tae Yong Kim, Gyungyup Gong, Suck Joon Hong, Won Bae Kim, Young Kee Shong
    Endocrinology and Metabolism.2010; 25(4): 316.     CrossRef
  • Prevalence of Thyroid Nodules Detected by Ultrasonography in Adults for Health Check-up and Analysis of Fine Needle Aspiration Cytology
    Jae Hoon Chung
    Journal of Korean Endocrine Society.2008; 23(6): 391.     CrossRef
  • Prevalence of Thyroid Nodules Detected by Ultrasonography in Adults for Health Check-Ups and Analysis of Fine Needle Aspiration Cytology
    Won Jun Kim, Joo Hyong Kim, Dong Won Park, Chang Beom Lee, Yong Soo Park, Dong Sum Kim, Woong Hwan Choi, Tae Wha Kim, You Hern Ahn
    Journal of Korean Endocrine Society.2008; 23(6): 413.     CrossRef
  • Trends Analysis of Characteristics of Thyroid Cancer Patients in One Medical Center
    Seung Hun Lee, Tae Yong Kim, Jin-Sook Ryu, Gyungyub Gong, Won Bae Kim, Seong Chul Kim, Suck Joon Hong, Young Kee Shong
    Journal of Korean Endocrine Society.2008; 23(1): 35.     CrossRef
  • Prevalence of Thyroid Nodules Detected by Ultrasonography in Adult Men Attending Health Check-ups
    Jung Hyun Kim, Sang Jun Park, Sang Eok Kim, Kwang Hee Lee, Il Kwon Cho, Sun Ik Jang, Jin Kwan Lee, Keum Soo Seo, Hyuck Po Kwon, Sung Chang Chung
    Journal of Korean Endocrine Society.2007; 22(2): 112.     CrossRef
Clinical Characteristics of Poorly Differentiated Carcinoma of the Thyroid and Comparison of Its Survival to the Tall Cell and Columnar Cell Variants of Papillary Carcinoma.
Tae Sik Jung, Jae Hoon Chung, Young Lyun Oh, Tae Yong Kim, Young Kee Shong, Won Bae Kim, Kyung Won Kim, Young Joo Park, Bo Youn Cho
J Korean Endocr Soc. 2006;21(2):132-141.   Published online April 1, 2006
DOI: https://doi.org/10.3803/jkes.2006.21.2.132
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BACKGROUND
Poorly differentiated carcinoma (PDC) of the thyroid includes tall and columnar cell variants (TCV) of the papillary carcinoma as well as the thyroid carcinoma with trabecular, insular and solid (TIS) growth patterns. There have been a few clinical studies on the PDC of the thyroid. We evaluated the clinical characteristics and the outcome of the PDC. METHODS: We investigated the clinicopathologic features of the thyroid carcinoma with TIS growth patterns (n = 46) and TCV of the papillary carcinoma (n = 14). We investigated the clinical features of ten patients diagnosed as PDC of the thyroid who had been undergone thyroidectomy for well differentiated carcinoma previously and compared these outcome with those of patients primarily diagnosed as PDC of the thyroid (n = 60). RESULTS: The clinical course of the thyroid carcinoma with TIS growth patterns was slightly more aggressive than that of TCV of the papillary carcinoma. However, disease-specific survivals of both cancers were not significantly different. Disease-specific survival was independently correlated with the presence of distant metastasis at diagnosis and high dose radioiodine therapy. The clinical features and outcome of the patients with PDC detected at recurred sites after operation for well-differentiated carcinoma were more aggressive than those diagnosed as PDC of the thyroid. CONCLUSION: The prognosis of the thyroid carcinoma with TIS growth patterns and TCV of the papillary carcinoma were similar. The PDC which was detected after thyroidectomy for well-differentiated carcinoma had worse prognosis than primarily diagnosed as PDC of the thyroid.
Role of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside in the Growth Regulation of Anaplastic Thyroid Cancer Cells Lines.
Ja Young Song, Tae Yong Kim, Won Bae Kim, Young Kee Shong, Yoon Soo Rhee, Ji Hye Suck, Suck Joon Hong
J Korean Endocr Soc. 2006;21(2):125-131.   Published online April 1, 2006
DOI: https://doi.org/10.3803/jkes.2008.21.2.125
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BACKGROUND
Anaplastic thyroid carcinoma is one of the most aggressive human cancers with a median survival of only 6 months. Local surgical tumor debulking combined with radio-chemotherapy is generally used to treat this malady, but the low success rate has prompted the search for new therapeutic targets. We used 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) as an AMP-activated protein kinase (AMPK) activator to induce growth suppression and apoptosis in the anaplastic thyroid carcinoma cells. METHODS: We investigated the effect of AICAR on the proliferation of thyroid cancer cell lines (ARO, WRO and FRO) by performing methyl-thiazoletetrazolium bromide assay. We wanted to see the effect of AICAR on the apoptosis and cell cycle of the thyroid cancer cells, and we wanted to determine the mechanism of these changes. RESULTS: The proliferation of all thyroid cancer cell lines was significantly inhibited by administration of AICAR. FRO was the most susceptible cell line to AICAR treatment and so further studies were then performed with this cell line. The suppressive effect of AICAR on cell proliferation was related with phosphorylation of AMPK and the increased apoptosis. Also, cell cycle analysis revealed that progression to the G2-M phase was arrested (S-phase arrest) by AICAR treatment. S-phase arrest was associated with the increased protein expression of p21. CONCLUSION: In the anaplastic thyroid cancer cell lines, AICAR inhibited proliferation due to the arrest in the S-phase; this was accompanied with the increased expression of p21. Overall, AMPK activation by AICAR or any other pharmacological agent could be a tempting potential target for thyroid cancer therapy.
Diagnosis of Impalpable Thyroid Nodule Detected by High-resolution Ultrasonography.
Tae Yong Kim, Won Bae Kim, Young Kee Shong
J Korean Endocr Soc. 2005;20(3):200-203.   Published online June 1, 2005
DOI: https://doi.org/10.3803/jkes.2005.20.3.200
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AbstractAbstract PDF
No abstract available.
Thyroid Hormone and Cardiovascular Disease.
Young Kee Shong, Won Bae Kim, Tae Young Kim
J Korean Endocr Soc. 2004;19(6):606-615.   Published online December 1, 2004
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AbstractAbstract PDF
No abstract available.
Role of Pexoxisome Proliferator Activated Receptor Gamma in Growth Regulation of Thyroid Cancer Cells.
Tae Yong Kim, Ja Young Song, Young Kee Shong, Won Bae Kim
J Korean Endocr Soc. 2004;19(5):511-521.   Published online October 1, 2004
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AbstractAbstract PDF
BACKGROUND
There is currently no effective option for the treatment of poorly differentiated thyroid carcinomas, so further studies are needed to evaluate new therapeutics. Thiazolinedione, an agonist of peroxisome proliferator activated receptor gamma (PPAR ), is known to suppress the growth of various tumor cell lines. This study was conducted to see if PPAR is involved in growth regulation of poorly differentiated thyroid cancer cells. SUBJECT AND METHODS: Thyroid cancer cell lines with a low degree differentiation, such as ARO and FRO cells were used, and their expression of PPAR mRNA checked. The effects of known agonists (rosiglitazone and 15-deoxy-delta12,14-prostglandin (15d-PGJ2)) and antagonists for PPAR (bisphenol A diglycidyl ether (BADGE)) on the growth of thyroid cancer cell lines expressing PPAR were evaluated by various methods, such as the methylthiazoletetrazolium bromide (MTT) assay, cell counts, and [3H]thymidine uptake. RESULTS: The expressions of PPAR were higher in ARO and FRO cells than in those of normal thyroid. Form the results of the MTT assay, the survival of ARO and FRO cells were found to decrease after administration of rosiglitazone or 15d-PGJ2. However, no change was observed after administration of BADGE. When the effect of rosiglitazone was evaluated by cell counting, there was significant decrease in number of ARO and FRO cells, but no change was observed after administration of 15d-PGJ2. Similar results were obtained using [3H]thymidine uptake. Thus, rosiglitazone treatment significantly decreased the [3H]thymidine uptake, whereas 15d-PGJ2 showed no significant effect. CONCLUSION: PPAR agonists (rosiglitazone and 15dPG-J2) suppressed the survival of ARO and FRO cells, undifferentiated thyroid cancer cell lines, with increased expressions of PPAR . However, the cell count and [3H] thymidine uptake were affected by rosiglitazone, but not by 15dPG-J2. This might suggest the antiproliferative effects of rosiglitazone are independent of PPAR ; and therefore, mediated by another unknown mechanism
Effect of Estrogen on H2O2 Induced Apoptosis of FRTL-5 Cells.
Won Bae Kim, Tae Yong Kim, Ja Young Song, Young Kee Shong
J Korean Endocr Soc. 2004;19(4):320-331.   Published online August 1, 2004
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BACKGROUND
Understanding the pathways and controlling mechanisms of thyrocyte apoptosis is important for the elucidation of the pathogenesis of goiter or thyroid cancer. A system for evaluating apoptosis, in FRTL-5 cells, triggered by hydrogen peroxide (H2O2), a highly likely apoptogenic signal in physiologic condition, was be set up to see the effects of TSH and estrogen on H2O2-induced apoptosis. METHOD: DNA laddering was used in the optimization process or the conditions of the set-up of system for the evaluation of apoptosis in the FRTL-5 cells. To quantify the apoptosis under the optimized conditions, histone-bound DNA fragments in the cytoplasm were measured by ELISA. RESULTS: 1) The optimized conditions for induction of apoptosis in the FRTL-5 cells by H2O2 were; observation of DNA laddering 18~24 hrs after the addition of 0.3 mM H2O2 to cells maintained in TSH-free, low serum containing media (5H1 or 5H0 media) for 48 hrs. 2) Exposure of the FRTL-5 cells to TSH (1 mU/L) for more than 48 hrs (6H0 media). before the addition of H2O2 significantly decreased the degree of apoptosis, compared to cells maintained under TSH-free conditions (0.98+/-0.21 vs. 2.27 0.11 arbitrary unit, p<0.05), whereas exposure for 24 hrs. did not. 3) Exposure of the FRTL-5 cells to high dose 17- estradiol (1-100 M) significantly decreased the degree of H2O2-induced apoptosis in a dose dependent manner. The addition of serum (1%) blunted the effects of estrogen on H2O2-induced apoptosis, and TSH totally abrogated the estrogen effect.Physiologic doses of estrogen (10~100 nM) showed no suppressive effects on H2O2-induced apoptosis in FRTL-5 cells. CONCLUSION: A system for evaluating apoptosis in FRTL-5 cells triggered by hydrogen peroxide (H2O2), a highly likely apoptogenic signal in physiologic condition, was set up, and found for the first time that high dose estrogen suppressed the H2O2-induced apoptosis in FRTL-5 cells
Search for "Proximal Histidine" of Thyroperoxidase Using Site Directed Mutagenesis.
Won Bae Kim, Young Kee Shong
J Korean Endocr Soc. 2003;18(4):371-378.   Published online August 1, 2003
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BACKGROUND
Thyroperoxidase (TPO), a transmembrane heme containing glycoprotein, catalyzes iodide organification and thyroid hormone synthesis. It is a single peptide making a loop with more than one disulfide bond. The tertiary conformational structure is essential for its enzymatic activity and immunogenicity. The proximal histidine is thought to play a major role in enzymatic activity since it is linked to the iron center of the heme. The crystal structure of TPO has not yet been reported, but some have suggested histidine 407 be a putative proximal histidine based on comparison of a.a. sequence for TPO and that for myeloperoxidase. METHODS: The putative histidine 407 and nearby histidine 414 were mutated to arginine to verify their role as the proximal histidine. Using site directed mutagenesis of wild type, human TPO cDNA, mutants H407R and H414R were made. Mutant cDNAs were transiently transfected into COS-7 cells, and the TPO enzyme activities were measured by guaiacol assay. Four cysteine residues around the putative proximal histidines were mutated to serine and their enzymatic activities were measured to check if they were involved in the formation of intra-molecular disulfide bonds. RESULTS: TPO protein expression of H407R- and H414R- transfected cells was confirmed by Western blot, using Hashimoto's IgG as primary antibody. Both the mutants H407R and H414R showed significant peroxidase enzymatic activity, although lower than those of the wild type. None of the cysteine mutants, C375S, C389S, C598S, and C655S, were detected by Hashimoto's IgG ordisplayed any enzymatic activity. CONCLUSION: These data suggest that neither histidine 407 nor histidine 414 functions as the "proximal histidine" in human TPO. All the cysteine residues checked (375, 389, 598, 655) might be involved in the formation of disulfide bonds in TPO molecules, but this hypothesis could not be confirmed. A further search for the other putative histidine residues using the same strategy is needed to define the structure-function relationship in the human TPO molecule.
Effect of LiCl on Iodine Kinetics in Thyroid Cancer Cell Lines Transduced by Recombinant Adenovirus Containing Sodium Iodide Symporter(NIS) Gene.
Won Bae Kim, Ja Young Song, Sung Min Han, Jeong Seok Yeo, Heui ran Lee, Young Kee Shong, Dae Hyuk Moon
J Korean Endocr Soc. 2003;18(2):166-176.   Published online April 1, 2003
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BACKGROUND
Lithium is known to increase the retention of iodide in the thyroid gland, or in well differentiated thyroid cancer tissue. The effects of lithium on the function of the sodium iodide symporter (NIS) protein, especially when the lithium is increased in the retention of iodide in NIS-producing cells, the effect of lithium, on the kinetics of undifferentiated thyroid cancer cells transduced by a recombinant adenovirus containing the NIS gene, were checked. METHOD: Human NIS cDNA was inserted into pAxCAwt, a recombinant adenoviral cosmid vector, where the E1 & E2 genes have been deleted, making Rad-hNIS, which was propagated in 293 cells. The iodide uptake was evaluated by the 125I uptake assay in the undifferentiated thyroid cancer cells, ARO, FRO and NPA, following the infection with Rad-hNIS (1 or 10 MOI) in the presence, or absence, of LiCl at optimized concentrations. The iodide efflux was evaluated by the 125I efflux assay, for 1 hour, in the same cells expressing the NIS in the presence, or absence, of LiCl. Similar experiments were performed in the normal thyroid cell line, FRTL-5, cultured in 6H5 media. RESULTS: LiCl, at concentrations over 1.0mM, caused a significant decrease in the cell viability, as evaluated by trypan blue dye exclusion, in a dose dependent manner. When infected with Rad-hNIS, the iodide uptake was not affected by the LiCl in the ARO or NPA cells. However, LiCl(0.1and 1.0mM) increased the iodide uptake by 50 to 100%(vs. control) in the Rad-hNIS transduced FRO cells. In the Rad-hNIS transduced FRO cells, the iodide was released rapidly from the cells, with only 20.7+/-4.8% of the iodide uptake remaining at 1 hour, which was no different in the presence of LiCl (24.5+/-7.9%). The iodide efflux was not affected by the LiCl in the FRTL-5 cells cultured in the presence of TSH. CONCLUSION: These results suggest that the lithium-induced iodide retention in the thyroid gland, or in well differentiated thyroid cancer tissue, is not caused by the effect of the lithium on the NIS function, or the function of proteins or channels, involved in iodide transport via cell membranes. Although the iodide uptake can be markedly increased by the expression of NIS, with the transduction of Rad-hNIS, in undifferentiated thyroid cancer cells, the iodide taken up is rapidly released from the cells. A method for inducing the iodide retention in the cell should be elucidated in order to render the NIS gene therapy effective.
Serum Thyroglobulin Levels Predicting Recurrence and Distant Metastasis after Surgery in Patients with Differentiated Thyroid Cancer.
Kyoung Soo Kim, Jin Sook Ryu, Suck Joon Hong, Won Bae Kim, Young Kee Shong
J Korean Endocr Soc. 2003;18(2):153-165.   Published online April 1, 2003
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BACKGROUND
Reports on serum thyroglobulin(Tg) levels being used to predict recurrence or distant metastasis during the follow-up of patients with differentiated thyroid cancer(DTC) has been inconsistent. In addition, there have been few reports that attempt to define the cut-off value of Tg for recurrence or distant metastasis obtained by a receiver operating characteristic(ROC) curve. As well, there are differences in opinions on what the value should be on the first serum Tg level measured just before radioactive iodine(RAI) ablation(Tg-RAI), during thyroxine administration (Tg-on), and after thyroxine withdrawal(Tg-off) during the follow-up. Reports on the positive predictive values(PPVs) and negative predictive values(NPVs) of these Tg values are rare. METHODS: A total of 205 patients(42 males, 163 females) with DTC were studied. All patients had undergone total or near-total thyroidectomy. After surgery and RAI ablation, annual thyroxine withdrawal 131I-whole body scan(WBS) with Tg measurements was performed. The mean duration of follow-up was 5.0 (1.4~7.4) years. The most sensitive and specific Tg values(cut-off values) for tumor recurrence and/or distant metastasis were selected by using ROC curves. We also calculated the PPVs and NPVs for recurrence and/or distant metastasis using two-by-two tables. RESULTS: Cut-off values of Tg-RAI, Tg-on, and Tg-off for recurrence were 11.8, 1.4, and 3.3ng/mL, respectively. For these values, the sensitivities were 85.4, 82.2, and 93.3%, with the specificitiesat 89.2, 92.4, and 88.0%. PPVs were 71.9, 77.1, and 77.0% while NPVs were 95.0, 94,4, and 97.8%. The cut-off values for distant metastasis were 27.4, 2.5, and 7.9ng/mL, respectively. For these cut-off values, the sensitivities were 86.7, 87.5, and 92.3%, with the specificities being 86.2, 90.8, and 80.2%. PPVs were 34.2, 46.7, and 25.0% and NPVs were 98.7, 98.8, and 99.3%. CONCLUSION: All three serum Tg levels were sensitive and specific markers for recurrence and distant metastasis. Their PPVs were low in contrast to the high NPVs. In comparison with Tg-on, Tg-off showed higher sensitivity and NPV as well as lower specificity and PPV. Therefore, in the case of higher Tg-on during the follow-up period, efforts to find recurrence and distant metastasis,such as 131I-WBS, should be done. In addition, regular measurement of Tg-off or Tg after stimulation with recombinant human TSH is recommended as a screening test.
Completion Thyroidectomy in Patient with Differentiated Thyroid Cancer Who Initially Underwent Ipsilateral Operation.
Eun Sook Kim, Jung Min Koh, Won Bae Kim, Suck Joon Hong, Young Kee Shong
J Korean Endocr Soc. 2002;17(5):657-663.   Published online October 1, 2002
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BACKGROUND
In some instances, thyroid cancer may be diagnosed only after resection of a putative or suspected benign nodule. In these cases a complete thyroidectomy is usually recommended to prevent recurrence. We analyzed the frequency of malignancy in the contralateral lobe after a complete thyroidectomy, and assessed the factors that may predict the presence of a malignancy, which might necessitate a complete thyroidectomy. METHODS: Between 1995 and 2001, 65 patients, who initially underwent a lobectomy and isthmectomy, but were finally diagnosed with differentiated thyroid carcinoma, underwent complete thyroidectomies. Their mean age was 39.8 +/- 12.4 years, ranging, 14 to 71 years. After initial surgery, 45 proved to have follicular carcinomas, 18 papillary carcinomas, 1 medullary and 1 insular carcinoma. The mean tumor size was 4.0 +/- 1.8 cm, ranging from 0.3 to 8.5 cm. After a complete thyroidectomy, the presence of a tumor the at contralateral lobe was assessed according to clinical parameters and the pathological findings in the ipsilateral lobe. RESULTS: The first surgeries revealed tumor multifocality in 27 cases, perithyroidal tumor extension in 4 and lymph node metastasis in 1. On completion of the thyroidectomy, 22 of the 65 patients had a malignancy in the contralateral lobe. Age, sex, size or the pathological primary tumor type, were not associated with the presence of additional tumors at the contralateral lobe. Tumor multifocality at the first surgery was the only significant variable to predict the presence of a tumor in the contralateral lobe. CONCLUSION: When thyroid cancer is diagnosed after ipsilateral surgery, the only predictive factor for the presence of a contralateral tumor was multifocality. We believe that a complete thyroidectomy is mandatory in these cases.
Thyroid Nodule.
Won Bae Kim, Young Kee Shong
J Korean Endocr Soc. 2002;17(4):445-459.   Published online August 1, 2002
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AbstractAbstract PDF
No abstract available.
Management of Differentiated Thyroid Cancer.
Young Kee Shog, Won Bae Kim
J Korean Endocr Soc. 2002;17(3):389-409.   Published online June 1, 2002
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AbstractAbstract PDF
No abstract available.
Recent Progress in Research On Autoimmune Thyroid Diseases.
Won Bae Kim
J Korean Endocr Soc. 2002;17(3):338-357.   Published online June 1, 2002
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AbstractAbstract PDF
No abstract available.
The Effects of Iodide on the Cellular Functions and Expression of Thyroid Autoantigens in Thyroid Cells.
Young Joo Park, Eun Shin Park, Tae Yong Kim, Hye Seung Jung, Hyeong Kyu Park, Do Joon Park, Won Bae Kim, Chan Soo Shin, Kyoung Soo Park, Seong Yeon Kim, Hong Kyu Lee, Bo Youn Cho
J Korean Endocr Soc. 2002;17(1):69-78.   Published online February 1, 2002
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BACKGROUND
Iodide has been known to control the function and the growth of the thyroid gland, and to be used as a substrate of thyroid hormone. Moreover, it has been suggested that excessive iodide stimulates the thyroid autoimmune responses. To evaluate the effects of iodide on thyrocytes, we investigated cell function and proliferation, or thyroid autoantigen expression after administering iodide to rats or FRTL-5 cells. MEHTODS AND RESULTS: Ten-weeks-old Sprague-Dawley rats were sacrificed after 7 days of NaI treatment. The expressions of thyroid autoantigens were examined by northern blot analysis. Chronic administration of iodide resulted in no effect on TSH receptor (TSHR) and thyroperoxidase (TPO) mRNA expression, while it increased thyroglobulin (TG) and diminished sodium-iodide symporter (NIS) mRNA expression. FRTL-5 cells were also treated with various concentrations of NaI. The generation of cAMP or iodide uptake was decreased, and the cellular growth was also inhibited by iodide. However, the expressions of all thyroid autoantigens (TSHR, TG, TPO, MHC class I and class II) except NIS were unchanged for 72 hours after iodide administration. The expression of NIS was mildly increased after 24 hours. CONCLUSION: Iodide resulted in decreased cell proliferation and cellular function of cAMP generation and iodide uptake. Chronic administration of iodide increased TG and diminished NIS mRNA expression in vivo but not in vitro
Effect of Class 2 Transactivator on Expression of Thyroid Transcription Factor-1 in FRTL-5 Cells.
Won Bae Kim, Tae Yong Kim, Young Joo Park, Jae Joon Koh, Do Joon Park, Bo Youn Cho
J Korean Endocr Soc. 2002;17(1):48-56.   Published online February 1, 2002
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AbstractAbstract PDF
BACKGROUND
Gamma-interferon (gamma-IFN) is known to suppress thyroperoxidase (TPO), thyroglobulin (Tg), thyrotropin receptor (TSHR) mRNA expression via unclarified mechanism. Thyroid transcription factor-1 (TTF-1) is a nuclear protein involved in the maximal expression and tissue specific expression of thyroid-specific antigens (TPO, Tg, TSHR, NIS) in thyrocytes. Although It's plausible that gamam-IFN induced suppression of thyroid-specific antigen expression may be mediated by decrease of TTF-1 expression, such an effect has not been documented yet. In this study we investigated the effect of gamma-IFN on the expression of TTF-1 in the rat thyroid cell, FRTL-5, and determined whether such an effect is mediated by sclass 2 transactivator (CIITA). METHEODS: The mRNA expression of TTF-1 was quantitated by northern blot analysis after treatment of gamma-IFN, and after expression of CIITA in FRTL-5 cells. Four different promoter constructs were made by cloning into the pRSV-luciferase vector, each contained 5'flanking sequence of different lengths (-5.18 kb, -4.11 kb, -1.94 kb, -1.15 kb) of rat TTF-1 gene. Effects of gamma-IFN and CIITA on promoter activities were analyzed by luciferase assay in FRTL-5 cells into which each promoter construct had been transfected by DEAE-dextran method. RESULTS: Steady state TTF-1 mRNA level at 48 h after gamma-IFN treatment (100 U/mL) was significantly decreased from that of the pre-treatment level (1.65+/-0.16 vs. unit, p<0.05). In all 4 promoter constructs gamma-IFN significantly suppressed promoter activities compared to the vector only transfected cells. CIITA expression in FRTL-5 cells significantly decreased the steady state TTF-1 mRNA level when compared to that in mock-transfected cells (1.69+/-0.31 vs. 1.17+/-0.44 arbitrary unit, p<0.05). CIITA expression in FRTL-5 cells caused suppression of promoter activities in -5.18 kb and -4.11 kb constructs, but had no effects on those activities in -1.94 kb; and -1.15 kb constructs. CONCLUSION: gamma-IFN, directly and indirectly via CIITA expression, suppressed the transcription of TTF-1 gene in the FRTL-5 cells. It may be one of the mechanisms involved in the gamma-IFN-induced suppression of thyroid-specific protein expressions in thyrocytes 1.25+/-0.27 arbitrary
TSH Receptor Antibodies: Recent Update and Clinical Applications.
Won Bae Kim, Young Kee Shong
J Korean Endocr Soc. 2002;17(1):10-19.   Published online February 1, 2002
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PDF
The Changes of Expression of Thyroid Specific Antigens in Aging.
Young Joo Park, Eun Shin Park, Tae Yong Kim, Sang Wan Kim, Hyeong Kyu Park, Do Joon Park, Won Bae Kim, Chan Soo Shin, Kyoung Soo Park, Seong Yeon Kim, Sang Chul Park, Hong Kyu Lee, Bo Youn Cho
J Korean Endocr Soc. 2001;16(4-5):457-466.   Published online October 1, 2001
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AbstractAbstract PDF
BACKGROUND
With the prevalence of serum antithyroglobulin(anti-TG) and antithyroperoxidase(anti-TPO) autoantibodies increasing with age, it has been suggested that changes of thyroid autoimmunity with aging are associated with endemic iodine intake. To understand the mechanism of aging-related increases of thyroid autoimmune response, we investigated the expression of thyroid specific autoantigens of aged phenotype, and compared them with those of young phenotype both in vivo and in vitro. METHODS: Sprague-Dawley rats were sacrificed at 5, 10 and 16 weeks(young), and at 23 months(aged). Their FRTL-5 thyroid cells were harvested at cell passages less than 10(fresh) or more than 30 (aged). The expression of thyroid autoantigens, sodium-iodide symporter(NIS), TSH receptor (TSHR), TG and TPO, were examined by northern blot analysis. To evaluate the effects of iodide, 1mM of NaI was added to the medium for 24 hours, and following incubation the expressions of MHC class I and class II were also examined. RESULTS: The expressions of TPO were markedly increased in the aged rats, and those of TG were moderately. However, NIS and TSHR showed no differences in their expression levels between aged rats and young rats. In vitro, there were no differences in the expressions of TG or TPO, nor of NIS or TSHR, between aged cells and fresh cells. Neither did Iodide exhibit any influence on the expression of MHC molecules in aged cells or fresh cells. CONCLUSION: The expression levels of TPO and TG were increased in aged rats, which may partially explain the mechanism of increasing thyroid autoimmunity with age.
Early Detection of Medullary Thyroid Cancer by Screening of the RET Proto-oncogene Germ Line Point Mutation in Family Members Affected with Hereditary Medullary Thyroid Cancer .
Sun Wook Kim, Tae Yong Kim, Young Joo Park, Won Bae Kim, Chan Soo Shin, Do Joon Park, Kyoung Soo Park, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee
J Korean Endocr Soc. 2001;16(1):54-64.   Published online February 1, 2001
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BACKGROUND
Conventional biochemical screening for family members with hereditary medullary thyroid cancer (MTC) is associated with problems of sensitivity and, specificity and it frequently detects gene carriers only after disease progression. Molecular genetic screening tests that detect germ-line point mutations of the RET proto-oncogene has changed our approach to hereditary MTC. In this study we screened members of a large Korean family that had a history of hereditary MTC by a molecular genetic method and propose a therapeutic approach in managing the disorder. METHODS: Using DNA acquired from peripheral blood leukocytes of the index patient, we performed PCR and direct sequencing of exon 10 of the RET proto-oncogene. PCR-RFLP using an Mbo II restriction enzyme was performed on family members who were at risk of MTC according to the family pedigree. Basal serum calcitonin level was determined in family members who had a point mutation of the RET proto-oncogene and a pentagastrin stimulation test was performed in 3 members. RESULTS: Genetic analysis in the index case revealed a mutation in exon 10, codon 618 of the RET proto-oncogene (TGC to AGC). Out of 28 members who were at risk of MTC, 24 members participated in the screening test. 9 members tested positive for a mutation in the same chromosomal location as the index patient by PCR-RFLP. Basal serum calcitonins were above 100 pg/mL in 2 members. 3 members who had a RET point muatation but a normal basal serum calcitonin level participated in the pentagastrin stimulation test and the results were negative in all members. We found a small medullary thyroid carcinoma that had a diameter of 0.2 cm in a 16 years old boy according to a negative pentagastrin stimulation test and who had received a prophylactic total thyroidectomy. He had no evidence of a lymph node metastasis. CONCLUSION: We detected a germ-line mutation of the RET proto-oncogene in codon 618 of Exon 10 by a molecular genetic method in a family with a hereditary MTC and found 9 members that had a negative history of MTC but had a RET point mutation. There was a very small MTC found in a 16 years old boy who had a normal pentagastrin stimulation test result. Therefore, It is recommended that a prophylactic total thyroidectomy be performed as well as in members that have a mutation of the RET proto-oncogene because MTC can metastasize early in its disease course.'
Treatment of Benign Nodular Thyroid disease.
Won Bae Kim
J Korean Endocr Soc. 2000;15(4-5):479-485.   Published online January 1, 2001
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No Abstract Available.
IL-10 Plasmid DNA Delivery in NOD Mice for the Prevention of Autoimmune Pancreatic Beta Cell Destruction.
Jae Joon Koh, Kyung Soo Ko, Jong Sang Park, Won Bae Kim, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee, San Goo Shin, Sung Wan Kim
J Korean Endocr Soc. 2000;15(2):262-271.   Published online January 1, 2001
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BACKGROUND
Recently, we have reported that biodegradable poly [-(4-aminobutyl)-L-glycolic acid] (PAGA) can condense and protect plasmid DNA from DNase I. In this study, we investigated whether the systemic administration of pCAGGS mouse IL-10 (mIL-10) expression plasmid complexed with PAGA can reduce the development of insulitis in non-obese diabetic (NOD) mice. METHODS: PAGA/mIL-10 plasmid complexes were stable for more than 60 minutes, but the naked DNA was destroyed within 10 minutes by DNase I. The PAGA/DNA complexes were injected into the tail vein of 3 week-old NOD mice. RESULTS: Serum mIL-10 level peaked at 5 days after injection, could be detected for more than 7 weeks. The prevalence of severe insulitis at 12 week-old NOD mice was markedly reduced by the intravenous injection of PAGA/DNA complex (15.7%) compared to that of naked DNA injection (34.5%) and non-treated controls (90.9%). In conclusion, systemic administration of pCAGGS mIL-10 plasmid/PAGA complexes can reduce the severity of insulitis in NOD mice. CONCLUSION: The study presents the PAGA/DNA complex has the potential for the application of the prevention of autoimmune diabetes mellitus.
Measurement of Anti-GAD65 Autoantibodies in Patients with Type 1 Diabetes Mellitus with / without Autoimmune Thyroid Diseases (Immunoblotting followed by Immunoprecipitation).
Yong Soo Park, Hye Won Park, Jin Bae Kim, Dong Sun Kim, Woong Hwan Choi, Tae Hwa Kim, Joon Yong Chung, Sei Won Yang, Won Bae Kim
J Korean Endocr Soc. 2000;15(2):190-203.   Published online January 1, 2001
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BACKGROUND
Type 1 diabetes mellitus is frequently associated with other autoimmune diseases. The broad concept of polyendocrinopathies takes into consideration that patients affected by at least one endocrine disease may have another autoimmune disorder or express specific autoantibodies. Anti-glutamic acid decarboxylase autoantibodies, now recognized as one of the major serological markers for type 1 diabetes has been reported to be higher in type 1 diabetes patients with autoimmune thyroid diseases (ATD) than in those without ATD. The objective of the present study was to evaluate the prevalences of GAD65 antibodies applying a newly developed assay(anti-GAD65) in type 1 diabetes patients with and without ATD. METHODS: We developed a new anti-GAD65 assay after mammalian expression of a recombinant GAD65 antigen. Since the detection of anti-GAD65 is rather complicated and insensitive due to inherent antigenic difference of antibody recognition in conventional assays, we applied this new approach in measuring anti-GAD autoantibodies and compared the result with ICA and anti-GAD measurement using the purified porcine GAD (anti-GAD) in 109 cases of type 1 diabetes, 29 of whom had concomitant ATD (mean age at diagnosis: 7.9 yr, mean duration of type 1 diabetes: 4.5 yrs). RESULTS: The overall prevalence of anti-GAD65 antibodies was 65% (71 of 109) in patients with Korean type 1 diabetes. Prevalences and titers of anti-GAD65 had not changed much after controlling for the duration and the status of concomitant ATD. In contrast, the prevalence of anti-GAD was 56%(61 of 109), while that of ICA(+) WAS 36% in type 1 diabetes patients. We found significant, but not strong association of anti-GAD65 either with anti-GAD(r=0.4, p<0.01) or with ICA(r=0.6, p< 0.001). CONCLUSION: From this, we could assess that autoantibodies are present at comparable sensitivity and specificity in Korean type 1 diabetes patients. This anti-GAD65 assay, another immunologic marker for type 1 diabetes might also confer disease susceptibility among Koreans, but no increase in the prevalence or in the titer in patients with ATD may suggest that this marker is unlikely to give much benefit, for the detection of the overlapping disease of type 1 diabetes and ATD.
Bone Turnover and Bone Mineral Density in Acromegaly.
Sun Wook Kim, Hee Jin Kim, Seon Hwa Lee, Won Bae Kim, Do Joon Park, Chan Soo Shin, Kyong Soo Park, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee
J Korean Endocr Soc. 1999;14(4):688-697.   Published online January 1, 2001
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BACKGROUND
Abnormalities of calcium homeostasis and bone remodelling were known in acromegaly, but controversy concerning the influence of chronically elevated serum growth hormone (GH)/insulin like growth factor-I (IGF-I) concentrations on bone metabolism has been existed. In this study, we assess the effect of chronically elevated serum GH/IGF-I levels on bone metabolism and bone mineral density (BMD) in patients with acromegaly and compare the markers of bone metabolism and BMD of active acromegaly according to gonadal function. METHODS: We measured biochemical markers of bone turnover and BMD in 50 acromegalic patients (41 active disease, 9 inactive disease) and 41 control subjects. RESULTS: Active acromegalic patients had significantly higher serum oteocalcin levels (13.8+/-7.7 versus 6.8+/-4.7, 6.0+/--3.4 ng/mL, p<0.05) and urinary type I cross-linked N-telopeptide (101.7+/-64.2 versus 49.3+/-33.3, 56.1+/-39.4 nM BCM/mM Cr, p<0.05) compared with inactive acromegaly and control subjects. Serum IGF-I levels correlated positively with serum osteocalcin levels(r=0.69, p<0.05) and urinary type I cross-linked N-telopeptide (r=0.44, p<0.05). In the female patients with active acromegaly, BMD (T-score) was elevated in the femoral neck(1.00+/-0.14 versus 0.89+/-0.12,p<0.05) and trochanter (0.88+/-0.15 versus 0.77+/-0.11, p<0.05), whereas BMD of lumbar spine(1.13+/- 0.17 versus 1.17+/-0.17, p>0.05) and femoral Ward's triangle (0.78+/-0.16 versus 0.77+0.13, p>0.05) were not different from those of control subjects. In the patients with active acromegaly, serum osteocalcin levels (16.4+/-8.8 versus 14.9+/-10.1 ng/mL, p>0.05) as well as urinary type I cross-linked N-telopeptide (104.8+/-68.1 versus 122.0+/-80.3 nM BCM/mM Cr, p>0.05) were not different according to gonadal function. Also, femoral and spinal BMD were not different according to the gonadal function. CONCLUSION: GH/IGF-I excess increase bone turnover and might achieve a positive bone balance at each remodelling cycle. Markers of bone turnover and BMD of skeletal bone were not influenced by gonadal function in the patients with active acromegaly.
Diagnostic Significance of Serum Thyroglobulin Measurement in the Follow - up of Patients with differentiated Thyroid Cancer.
Seon Hwa Lee, Byung Sool Moon, Sun Wook Kim, Jae Joon Koh, Do Joon Park, Won Bae Kim, Bo Youn Cho, Hong Kyu Lee
J Korean Endocr Soc. 1999;14(4):667-678.   Published online January 1, 2001
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BACKGROUND
Although serum thyroglobulin (Tg) has been proved to be a good tumor marker in the follow-up of the well differentiated thyroid cancer, some patients show low detectable Tg with negative 131I scan. In the present study, we tried to determine the lowest level of serum Tg which suggests requirement of aggressive work-up for the recurrent or metastatic thyroid cancer. METHODS: Serum Tg levels were measured in 102 patients with well differentiated thyroid cancer who had underwent thyroidectomy followed by 131I ablative therapy. Of 102 patients, 44 patients had no remnant thyroid tissue, while 58 patients had remnant thyroid. Serum Tg levels were measured while TSH-suppressive dose of T4 was administered (on T4 therapy) and then T4 was discontinued for 4 weeks to increase serum TSH level (off T4 therapy), then serum Tg levels were analyzed in relation to the presence or absence of recurrent or metastatic thyroid cancer, assessed by I scan and operation with reference to the physical examination, chest X-ray and thyroid ultrasonogram. RESULTS: Of 102 patients, 16 patients were found to have recurrent or matastatic thyroid cancer. Among them, 10 patients didnt have any remnant thyroid, while 6 patients had remnant thyroid. Serum Tg was undetectable on T4 therapy in 6 patients, but rose higher than 30 ng/mL off T4 therapy in 2 patients, while Tg remained undetectable in other 4 patients. In all 10 patients whoseTg levels were higher than 1 ng/mL. on T4 therapy, Tg rose higher than 30 ng/mL off T4 therapy. The best cut-off value of serum Tg which suggests recurrent or metastatic disease in patients without remnant thyroid was 3 ng/mL on T therapy (sensitivity 60%, specificity 91%, accuracy 84%) and 30 ng/mL off T4 therapy (sensitivity 80%, specificity 75%, accuracy 77%). In patients with remnant thyroid, cut-off value of serum Tg could not be determined because of the low sensitivity and specificity. CONCLUSION: In patients with well differentiated thyroid cancer who have no remnant thyroid, serum Tg level lower than 3 ng/mL on T4 therapy can warrant following-up of patients only with such clinical measures only such as physical examination and thyroid ultrasonogram. However, patients with Tg level of 3 ng/mL or more requires Tg measurements off T4 therapy and 131I scan to evaluate the possibility of recurrent or metastatic thyroid cancer.
Clinical Features Associated with an Increased Risk of Malignancy in Indeterminate Group by Find Needle Aspiration of Thyroid Nodules.
Seon Hwa Lee, Sun Wook Kim, Do Joon Park, Won Bae Kim, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee, Chang Soon Koh
J Korean Endocr Soc. 1999;14(3):505-513.   Published online January 1, 2001
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BACKGROUND
The recommended management of patients who have cytologic diagnosis of indeterminate group by fine fine needle aspiration (FNA) in thyroid nodules is controversial. Our objective was to identify the incidence of malignancy through thyroidectomy in indeterminate group and clinical features associated with an increased risk of malignancy that might guide future practice. METHODS: We retrospectively reviewed the medical records of 222 patients who had cytologic diagnosis of indeterminate group by FNA in thyroid nodules at Seoul National University Hospital from Jan. 1990 to Aug. 1998. Patients characteristics and clinical features were compared between benign and malignant nodules classified as pathologic findings through thyroidectomy. RESULTS: The frequency of indeterminate group was 6% (222/3981) among patients underwent thyroid FNA. The frequency of malignant nodules was 47.4% (64/135) among 135 patients underwent thyroidectomy. Among clinical features, rapid increase in size (7.0% vs 20.3%, p=0.024), local symptoms such as dysphagia, hoarseness, pain (1.4% vs 15.6%, p=0.003), fixation (4.4% vs 35.7%, p<0.001), hard consistency(15.7% vs 59.7%, p<0.001) and irregular surface(6.3% vs 25.6%, p=0.001) were significantly more common in malignant nodules than in benign nodules. However, clinical features such as mean age of patients, male sex, presence of past history of benign thyroid disease, family history of benign thyroid disease, solitary nodule, presence of cervical lymph nodes, mean size of nodules and cold nodules by thyroid scan in malignant nodules were not significantly different from that in benign nodules. Among clinical features that were significantly more common in malignant nodules, fixation(p=0.042) and presence of local symptoms (p=0.043) were significantly independent risk factors predictive of malignancy. CONCLUSION: Its better to recommend thyroidectomy in patients with clinical features such as presence of local symptoms, fixed nodule and hard nodule in indeterminate group, in otherwise to decide treatment with repeated FNAs when clinical features such as patients symptoms and physical examinations of nodule change through regular follow-up.
Prevalence Thyroid Cancer in Patients with Cold Thyroid Nodules in Relation to Sex, Age, And Multinodularity.
Won Bae Kim, Hyun Kyung Chung, Chang Hoon Yim, Do Joon Park, Sung Yeon Kim, Bo Yeon Cho, Hong Gyu Lee
J Korean Endocr Soc. 1998;13(3):366-372.   Published online January 1, 2001
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BACKGROUND
We evaluated the prevalence of thyroid cancer in patients with cold thyroid nodules and the impact of sex, age, hardness of nodule, and multinodularity as factors able to predict the probability of malignancy in patients with nodular thyroid diseases. METHODS: We examined a 728 patients who visited Seoul National University Hospital with one or more cold thyroid nodules between Jan. 1996 and Dec. 1997. After clinical evaluations including medical history, physical examinations(size, hardness and multiplicity of nodule), fine needle aspiration biopsies and cytologic examinations were carried out. RESULTS: Among the 728 cases, 76 cases(10.4%) were diagnosed as cancer and 602 cases (82.6%) were diagnosed as benign nodule. The prevalence of cancer was significantly lower in female patients with cold nodules(9.4%, 62/662) than in males(17.5%, 11/63)(p=0.041). Age was an important factor in both sexes. The proportion of nodules that were malignant was lower in patients of 20-60 years old(8,9%, 56/632) than patients younger than 20 years old(1S.1%, 2/11) or older than 60 years old(18.3%, 15/82)(p=0.019). The prevalence of cancer was significantly higher in hard nodules(36.3%, 41/113) than firm(5.2%, 30/574) or soft nodules(5.3%, 2/38)(p= 0.001). There was no size difference between malignant(25.2 +- 13.7mm) and benign nodules(25.3 +- 8.9mm)(p=0.9425). The prevalence of thyroid cancer in solitary nodule(10.6%, 63/593) was not different from that in multiple nodules(7.6%, 10/132)(p=0.293). CONCLUSION: Our data suggest that thyroid nodules of the patients who are younger than 20 years old or older than 60 years old, male, as well as hard nodule require more careful evaluation for the risk of thyroid malignancies.
The Incidence of Postpartum Thyroiditis and Effect of High Iodine Intake on it in Korean Women.
Won Bae Kim, Chang Hoon Yim, Kyung Soo Park, Byoung Sool Moon, Jae Hoon Lee, Hye Won Jun, Ho Jun Jin, Sung Yeon Kim, Bo Yeon Cho, Hong Gyu Lee
J Korean Endocr Soc. 1998;13(3):339-350.   Published online January 1, 2001
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BACKGROUND
Postpartum thyroiditis(PPT) is one of syndromes of thyroid dysfunction that occurs in the first year after parturition. Reported incidence of PPT is 3.9-8.2% of postpartum women in several studies from different countries. The fact that 52-100% of patients with PPT have thyroid autoantibodies, and that lymphocytic infiltration of thyroid gland is the characteristic pathological feature of PPT suggest that PPT is an autoimmune disease. High iodine intake in short term period is known to aggrevate the experimental autoimmune thyroiditis. This study was performed to investigate the incidence and clinical features of PPT in Korean postpartum women who usually ingest excessive amount of idine in immediate postpartum period and to investigate the predictive value of thyroid autoantibodies in the development of PPT in them. METHOD: Between March 1996 and February 1997, 99 women without previous history of any thyroid disease who delivered babies at Boramae hospital were enrolled. Thyroid function parameters(T3, T4, free T4, TSH), thyroid autoantibodies(anti-microsomal antibody, anti-thyroglobulin antibody) and urinary iodine excretion were measured prospectively before and 1, 3 months after delivery. Dietary iodine intake during postpartum period was evaluated by questionnaire, and clinical parameters were followed up. RESULTS: During 3 months of observation, PPT developed in 8.1%(8/99) of postpartum women. Five cases had typical course having thyrotoxic phase and the other 3 cases had hypothyroid phase without toxic phase. However, only one of those required thyroid hormone replacement therapy in the latter group. There were no differences in age, baseline thyroid function parameters, parity, percent cases with family history of thyroid disease between those developed PPT (n=8) and those did not develop PPT(n=91). Duration of high iodine intake(3.8 +- 0.5 wk. vs. 3.7 +- 0.8 wk., p>0.05), total ingested amount of high iodine diet(77 +- 28 vs. 79 +- 24 bowels of miyokguk, p)0.05), and the urinary iodine excretion(1.9 +- 1.4 mg/g creatinine vs. 3.7 +- 3.7mg/g creatinine, p0.05) at 1 month postpartum were not different between two groups. Of 99 total subjects, anti-microsomal antibody(AMA) was present in 13.1%(13/99) before delivery in their sera. Positive predictive value of the presence of AMA before delivery in predicting the development of PPT was 30.8%. CONCLUSION: The fact that incidence of PPT in normal Korean postpartum women who usually have high iodine intake in immediate postpartum period is not higher than those of other countries, and that there was no difference in the amount of iodine intake between those developed PPT and those did not suggest that high iodine intake in immediate postpartum period do not influence on the incidence of PPT. The presence of AMA before delivery had low specificity in prediction of development of PPT, so the measurement of AMA seems not to be a useful screening test.
Usefulness of Immunoglobulin Fraction Precipitated with Polyethylene Glycol in Assay for TSH Receptor Antibodies using Chinese Hamster Overy Cells Expressing Human TSH Receptors.
Won Bae Kim, Hyun Kyung Chung, Chang Soon Koh, Chang Hoon Yim, Do Joon Park, Bo Yeon Cho, Hong Gyu Lee
J Korean Endocr Soc. 1998;13(2):167-180.   Published online January 1, 2001
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BACKGROUND
Graves' disease and primary myxedema are thought to be caused by the action of TSH receptor autoantibodies(thyroid stimulating antibody; TSAb & thyroid stimulation blocking antibody; TSBAb). Thus, detection of these antibodies is crucial in diagnosis and in follow up of those patients. Recently, a sensitive method using human TSH receptor transfected Chinese Hamster Ovary(CHO) cells has been developed. However, the complexity of IgG purification procedure is considered as a limitation for its clinical application as a routine test. The aim of this study is to determine whether polyethylene glycol(PEG)-precipitated immunogiobuIin fraction could substitute for purified IgG. METHODS: We developed optimal conditions for TSAb and TSBAb assays using crude, PEG precipitated immunoglobulin fraction; and evaluated the correlation of TSAb and TSBAb activities between thase measured using crude immunoglobulin fraction and purified IgG to clarify the usefulness of PEG-precipitated immunoglobulin fraction. TSH receptor expressing wild type CHO cells were used in TSAb and CHO cells expressing chimeric TSH receptor(Mc2; 90-165 amino acid residues were substituted by those of rat LH/CG receptar) were used in TSBAb assay to minimize the possible disturbing effects of TSAb in serum. RESULTS: The optimal serum amount for TSAb and TSBAb assay using PEG-precipitated immunoglobulin fraction were 250mL serum equivalent/well and 50mL serum equivalent/well, respectively. The optimal incubation time for both assays were 2 homs, and aptimal ccrncentration of bTSH for TSBAb assay was 0.1U/L. TSAb activities measured with PEG-precipitated immunoglobulin were significantly correlated with those measured with purified IgG in 26 patients with Graves diseases(r=0.93, p<0.001). Although TSBAb activities measured using PEG-precipitated imrnunoglobulin were conelated with those measured using purified IgG in 20 patients with primary myxedema(r=0.86, p<0.001), the positive rate in TSBAb assay using PEG-precipitated immunoglobulin was lower than that of usmg purified IgG(20% v.s. 65%) because of negative conversion of TSBAb activities in samples with weakly positive TSBAb activities measured using purified IgG. CONCLUSION: PEG-precipitated immunoglobulin fraction could be used instead of purified IgG in TSAb assay using hTSHR-tranasfected wild type CHO cells with equal sensitivity and specificity. This simple and practical TSAb assay using PEG-precipitated immunoglobulin in hTSHR-transfected CHO cells would be useful in clinica1 practiee.
Analysis of Prognostic Factors Determining the Recurrences in Patients with Papillary Thyroid Cancer After Surgical Treatment.
Jae Seok Jeon, Won Bae Kim, Hyun Kyung Chung, Bo Youn Cho, Hong Kyu Lee, Chang Soon Koh, Do Joon Park, Sun Wook Kim
J Korean Endocr Soc. 1997;12(3):421-432.   Published online January 1, 2001
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BACKGROUND
It is important to recognize the independent prognostic factors of papillary carcinoma of thyroid in therapeutic and follow up planning. However, its good prognosis and its low prevalence make it difficult to analyze prognostic factors determining patients survival in a relatively short period of time. We retrospectively investigated the independent prognostic factors for determining disease recurrence after surgery which, in adults, are known to be closely related to the prognosis of cancer. METHOD: We retrospectively reviewed the clinical records of 456 patients (male 70, female 381, unknown 5, mean age of 43.9+-12.9 years) who had visited the thyroid clinic in Seoul National University Hospital and analyzed the data with statistical software program. RESULTS: 1) At initial visit, chief complaint of the patients was abnormal neck mass in 90 percent. 2) In preoperative thyroid scan study, 82% showed cold area and 16% showed diffuse enlargement. 3) Of the 50 recurrent cases after surgery (11.5% of the total cases), 39 cases (78%) had recurred disease in neck area and 11 cases (22%) had recurrences at distant sites. (Lung 9 cases, Brain I case, Mediastinum 1case) 4) Statistically significant risk factors for recurrence after surgery were male sex, size of tumor (above 4.5cm in this study), extrathyroidal invasion of cancer, involvement of resection margin and no remnant ablation of thyroid tissue using radioiodine. CONCLUSION: Through retrospective study, we presented some clinical characteristics of papillary thyroid cancer in Korea and independent risk factors of cancer recurrences after surgery.
Changes in Properties of Thyrotropin Receptor Antibodies Following Radioiodine Treatment in Patients with Graves' Disease.
Won Bae Kim, Hyun Kyung Chung, Bo Youn Cho, Hong Kyu Lee, Chang Soon Koh, Do Joon Park, Yeon Sahng Oh
J Korean Endocr Soc. 1997;12(2):194-206.   Published online January 1, 2001
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BACKGROUND
It has been suggested that thyroid stimulation blocking antibody (TSBAb) is involved in the development of early hypothyroidism after radioiodine treatment in patient with Graves disease. However, previous studies have reported the effect of radioiodine treatment on overall changes of TSH receptor antibodies without detailed observation of changes in properties of TSH receptor antibodies. The aim of this study is to evaluate the effect of radioiodine treatment on thyroid stimulation antibody (TSAb) or on thyroid stimulation blocking antibody (TSBAb) activities and to see whether the appearance of TSBAb after radioiodine treatment is involved in the development of early hypothyroidism in patients with Graves disease. METHODS: The activities of TSAb, TSBAb were measured serially with human TSH receptor transfected Chinese hamster ovary (CHO) cells in 36 patients with Graves disease who received 131I treatment. In addition to the wild type TSH receptor-expressing cells, we used a chimeric receptor that 90-165 amino acid residues were substituted by those of rat LH/CG receptor (Mc2) for measurement of TSBAb without interference by the presence of TSAb and for evaluation of TSAb epitope spreading. We evaluated the association of early hypothyroidism after 131I treatment with changes of various immunologic parameters. RESULTS: In 14 (39%) of 36 patients, TSBAb activities were present in their sera before or after 131I treatment. Four of them had TSBAb activities before 131 treatment, and 12 newly acquired TSBAb activities after 131I treatment. The existence of TSBAb was not associated with the development of early hypothyroidism after 131I treatment but with low TSAb activities before 131 treatment, high thyroidal uptake of 131I given and with old age. The phenomena of epitope spreading measured by TSAb with Mc2 mutant clone before and after 131I treatment was not infrequent, but it had no clinical relevance. CONCLUSION: These results suggest that the existence of TSBAb may be not a major factor in the development of early hypothyroidism after radioiodine treatment in Graves disease. Other factors such as TSAb activities before radioiodine treatment, the efficiency of thyroidal uptake of 131I or old age are associated with the development of early hypothyroidism.
Heterogeneity of TSH Receptor Autoantibodies in Autoimmune Thyroid Disease.
Won Bae Kim, Bo Youn Cho, Kyoung Ah Kim, Jae Hoon Chung, Young Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim
J Korean Endocr Soc. 1997;12(2):176-193.   Published online January 1, 2001
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BACKGROUND
It has been known that most of thyroid stimulating antibodies (TSAbs) may interact with epitopes near N-terminal, and thyroid stimulation blocking antibodies (TSBAbs) near C-terminal on the extracellular domain of TSH receptor. However, many authors have reported different results about epitopes reacting with TSH receptor autoantibody (TRAb). TSBAbs inhibit thyroid stimulation of TSH and TSAbs at the receptor level. However, it has been reported that there are some TSBAbs which bind to the other sites, not TSH receptor, or block post-reeeptor process. These findings raise the possibility that TRAbs may be heterogeneous according to the mechanism of action. In order to investigate the heterogeneity of TRAb, we undertook immuno-precipitation using synthetic peptides of TSH receptor and measured TRAb activities by FRTL-5 cells and chimeric CHO cells. METHODS: We studied 102 patients with autoimmune thyroid disease (Graves disease 32, Hashimotos thyroiditis 29, atrophic thyroiditis 41) and 35 healthy persons. Three synthetic peptide fragments of TSH receptor were used to perform immunoprecipitation with serum or IgG of patients and healthy persons, TSAb and TSBAb activities were measured by FRTL-5 cells and CHO cells transfected with wild-type and 2 mutant TSH receptor cDNA (Mc2, Mc1+2). Mc2 and Mcl+2 were rnade to substitute amino acid residues of 90-165, 8-165 of the TSH receptor with corresponding residues of LH/CG receptor, respectively. RESULTS: Two out of 10 IgGs extracted from Graves disease and 2 out of 9 IgGs from atrophic thyroiditis had specific bidings over 0.84% in immunoprecipitation with peptide I (amino acid residue 35-50). Four out of 18 IgGs from Graves disease, 9 out of 41 IgGs from atrophic thyroiditis, and 6 out of 14 IgGs from Hashimotos thyroiditis had specific bidings over 0.84% in immunoprecipitation with peptide II (amino acid residue 317-332). Only 2 out of 10 IgGs from Graves disease had specific bidings over 0.84% in immunoprecipitation with peptide III (amino acid residue 341-358). When 10 IgGs extracted from Graves disease were reacted with wild-type, Mc2, and Mcl+2 CHO cells, 7 IgGs in wild-type and 4 IgGs in Mc2 had positive for TSAb activities. In 10 IgGs from atrophic thyroiditis, 5 in wild-type, 5 in Mc2, and 3 in Mcl+2 CHO cells had positive for TSBAb activities. In Hashimoto's thyroiditis, only 1 with hyperthyroidism had positive for TSAb activity in wild-type and 1 with hypothyroidism had positive for TSBAb activities in both of wild-type and Mc2 CHO cells. Therefore, patients with Graves disease were divided into at least 3 groups according to the TSAb activities measured by wild-type, Mc2, Mcl+ 2 CHO cells and TBII activities. And patients with atrophic thyroiditis were divided into at least 4 groups according to the TBII activities, TSBAb activities by wild-type, Mc2, Mcl+2 CHO cells and FRTL-5 cells. CONCLUSION: From these results, epitopes of TSH receptor reacting with TSAb or TSBAb in autoimmune thyroid disease may be scattered in the TSH receptor, although epitopes of TSAb tend to be near N-terminal and those of TSBAb near C-terminal. Graves disease or atrophic thyroiditis were divided into 3 or 4 groups according to the TBII and TRAb activities. Therefore, TRAb detected in autoimmune thyroid disease may be heterogenous.
Clinical Significance and Immunological Characteristics of Blocking TSH Receptor Antibodies in Patients with Hashimoto's Thyroiditis.
Won Bae Kim, Hyun Kyung Chung, Bo Youn Cho, Hong Kyu Lee, Chang Soon Koh, Do Joon Park
J Korean Endocr Soc. 1997;12(1):33-44.   Published online January 1, 2001
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BACKGROUND
TSH receptor blocking antibody (TRBAb) is a pathogenic factor in the vast majority of patients with primary myxedema. It has been reported that TRBAbs are found in some patients with chronic goitrous autoimmune thyroiditis (Hashimoto's thyroiditis), but the significance or the role of TRBAb in Hashimotos thyroiditis is not clear, We recently reported that hTSHR-CHO cells which express the functional human TSH receptors are more sensitive and are better in detecting functional TSH receptor antibodies in Graves patients than FRTL-5 cells. We are to investigate the biological role of TRBAb in Hashimotos thyroiditis by measuring thyroid stimulation blocking antibody (TSBAb) activities of Hashimoto's IgG's using hTSHR-CHO cells. Moreover, we are to see if there is any difference in epitope recognition between Hashimotos TRBAb and myxedema's TRBAb by measuring TSBAb activities with mutant receptor expressing cell lines, Mcl+2 and Mc 2 in those patients. METHOD: We measured TSBAb activities of IgGs from patients with primary myxedema (PM, n= 10) and those with hypothyroid (n 20) or euthyroid (n 17) Hashimoto's thyroiditis (HT) using wild type hTSHR-CHO cells (WT) and two chimeric receptor expressing cell lines, Mcl+2 and Mc2. RESULTS: TSBAb activities measured by WT were higher in hypothyroid HT than in euthyroid HT (30.0+-23.2% vs. 6.1+-28.7, p<0.05), and TSBAb-positive rate tend to be higher in the former (20%, 5/20) than in the latter (0%, 0/17, p=0.07). TRBAbs from PM (n=4) had high TBII activities and had persistent blocking activities despite of the replacement of amino acid residue 8~165 of extracellular domain of TSHR with those of rat LH/CGR (Mcl +2). However, TRBAbs from HT (n=4) had no TBII activity at all and lost blocking activities when measured with Mcl+2. CONCLUSION: TRBAbs are found in 20% of hypothyroid patients with Hashimotos thyroiditis in assay using hTSHR-CHO cells, and they seem to play a role in the development of hypothyroidism in some patients with Hashimotos thyroiditis. TRBAbs of Hashimotos thyroiditis are different in epitope recognition from TRBAbs of primary myxedema.
Measurements of Thyroid Stimulation Blocking Antibody Activities by Chinese Hamster Ovary ( CHO ) cells Expressing Human TSH Receptors in Patients with Primary Hypothyroidism.
Won Bae Kim, Bo Youn Cho, Do Joon Park
J Korean Endocr Soc. 1997;12(1):18-32.   Published online January 1, 2001
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BACKGROUND
The Chinese hamster ovary cells transfected with human TSH receptor cDNA (hTSHR-CHO), expressing functional human TSH receptors, are known to be more sensitive in detection of thyroid stimulating antibodies than FRTL-5 cells. There has been no report on the usefulness of these cells to measure thyroid stimulation blocking antibody (TSBAb) activity which is frequently found in patients with primary myxedema, METHODS: We established the optimal assay condition of measurement of TSBAb using hTSHR-CHO cells, and simultaneously measured TSBAb activities with FRTL-5 cells and with hTSHR-CHO cells in 49 patients with primary myxedema, compared them with their thyrotropin binding inhibitor immunoglobulin (TBII) activities. RESULTS: 1) hTSHR-CHO cells specifically bound bTSH and were stimulated by bTSH in terms of cyclic AMP generation in a dose dependent manner. 2) Myxedema IgG suppressed TSH-stimulated cAMP production of hTSHR-CHO cells in a dose dependent manner reaching plateau at the concentration of I g/L. Normal pooled IgG has no suppressive action at the concentration of less than 1 g/L, but caused significant suppression at the concentration of greater than 1g/L. 3) TSBAb activities measured by hTSHR-CHO cells in 49 patients with primary myxedema were as follows: Four of 25 TBII-negative cases (16%) and 22 of 24 TBII-positive cases (92%) had TSBAb activities. Most of TSBAb positive patients (95%), especially in TBII positive cases, showed very high activities of more than 90%. 4) TSBAb activities measured by hTSHR-CHO cells and those by FRTL-5 cells were both positive in 24 patients (49%), both negative in 18 patients (37%), and were discrepant in 7 patients (14%). The TSBAb activities measured with hTSHR-CHO cells and those measured with FRTL-5 cells were significantly correlated (r=0.71, p< 0.01). 5) Forty five percent of patients with primary myxedema had all of 3 kinds of activities (TBII, hTSHR-CHO cell TSBAb, FRTL-5 cell TSBAb), 37% of them had none of 3 activities and 18% of them had 1 or 2 kinds of activities only. CONCLUSION: The usefulness of hTSHR-CHO cells in measurements of TSBAb activities were confirmed. The TSBAb activities of most patients with primary myxedema measured by hTSHR-CHO cells were concordant with those measured by FRTL-5 cells. However, a small subset of patients (18%) had discrepant results in assays of TSH receptor antibodies according to the differences in TSH receptors (rat, human and porcine) used in assay. Such discrepancy may be explained by heterogeneity in epitopes for blocking TSH receptor antibodies.
The Incidence of Thyroid Autoantibody in Subacute Thyroiditis and the Clinical Characteristics of Greeping Thyroiditis.
Jae Seok Jeon, Won Bae Kim, Hae Young Park, Young Joo Park, Hyun Kyung Chung, Sang Jeon Choi, Chan Soo Shin, Kyoung Soo Park, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee, Chang Soon Koh
J Korean Endocr Soc. 1996;11(4):438-446.   Published online November 7, 2019
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Background
Subacute thyroiditis is a spontaneously resolving inflammatory disorder of thyroid gland, usually associated with painful goiter and short-lived thyrotoxicosis. Although its etiology is yet to be established, much evidence suggests viral infections and genetic factors play important roles. Usually, both lobes of thyroid gland are involved simultaneously, but in some patients one lobe is involved first and the other later(creeping thyroiditis), Thyroid autoantibodies which might appear probably due to inflammatory release of thyroid antigens, are found in a variable number of patients with subacute thyroiditis. However there have been few detailed reports on their incidence in Korean patients with subacute thyroiditis. So, we were to see the elinical characteristics of patients with subacute thyroiditis with special regards to the incidence of thyroid autoantibodies and to the incidence and characteristics of creeping thyroiditis, Methods: We reviewed the clinical records of 85 patients with subacute thyroiditis(7 men and 78 wornen, meam age of 43+9 years) who had visited the thyroid clinic in Seoul National University Hospital between 1986 and 1994. Results: At initial visit, the incidenees of thyroid autoantibodies were as follows: anti- microsomal antibody 7.8%, anti-thyroglobulin antibody 22.1%, and thyratropin binding inhibitor inununglobulin 6.3%. During the follow-up period, thyroid autoantibodies appeared most frequently between the first and the second month after initial visit. Compared to those with non-creeping thyroiditis, the patients with creeping thyroiditis(21.4%) had nonspecific systemic sy~rnptoms more frequently(89% vs. 42%, p<0.05). They required steroid therapy more ftequently(89% vs. 52%, p <0.05), and needed longer duration of treatment(9.3+6.2weeks vs, 4.7+3.7weeks, p<0.05). The incidence of abnormalities in liver function and the incidence of thyroid autoantibodies were higher in non-creeping thyroiditis group. Conclusion: In accordance with previous reports, thyroid autoantibodies were detected in only a small portion of Korean patients with subacute thyroiditis. Rather different clinical manifestations and different incidences of thyroid autoantibodies between ereeping group and non-creeping group suggest differences in the pathogenetic mechanisms between those two groups. However, there is need for further study to validate such observation and to elucidate the mechanisms.
A Case of Symptomatic Severe Hypercalcemia as Initial Manifestation of Hyperthyroidism.
Hye Young Park, Won Bae Kim, Hyeon Kyu Kim, Chan Soo Shin, Seong Yeon Kim, Bo Youn Cho, Hong Gyu Lee, Chang Soon Koh
J Korean Endocr Soc. 1996;11(1):124-126.   Published online November 7, 2019
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No abstract available.
Clinical Characteristics of Graves' Disease Patients with Undetectable Thyrotropin Binding Inhibitor Immunoglubulin (TB2).
Bo Youn Cho, Won Bae Kim, Hong Gyu Lee, Chang Soon Koh, Seong Yeon Kim, Seok In Lee, Jae Seok Chun, Kyung Soo Park
J Korean Endocr Soc. 1996;11(1):68-74.   Published online November 7, 2019
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Background
Graves disease is an autoimmune disease caused by TSH receptor antibodies. Thyrotropin binding inhibitor immunoglobulins(TBII) are detected in most Graves patients, but some patients have no TBII activities in their sera. It is unknown whether the clinical features of TBII-positive patients are different from those of TBII-negative patients. Methods: To evaluate the prevalence of TBII-negative Graves' patients and its clinical differences from TBII-positive patients, we examined TBII by radioreceptor assay in 686 consecutive untreated Graves patients. We found 84 TBII-negative patients(15 men and 69 women, mean age ±EM: 40.9±.4 years) and compared their clinical characteristics with 87 TBII-positive patients (22 men and 65 women, mean age±EM: 39.9±.5 years) who were selected randomly from the same patients group. Results: In this study, TBII was undetectable in 12.2% of patients with Graves' disease(84 of 686). TBII-negative group had a less weight loss than TBII-positive group. However, there was no significant differences in age, sex ratio, prevalence of ophthalmopathy, duration of illness and positive rate of family history for thyroid diseases between TBII-negative and -positive groups. Serum total T or T levels were not different from each other, but T3-uptake was significantly higher in TBII-positive group than that in TBII-negative group, suggesting that the free hormone levels in TBII-negative group might be lower. The thyroid uptake of 99mTcO4 was significantly higher in TBII positive group than that in TBII-negative group. Thyroid autoantibodies, including antimicrosomal and antithyroglobulin antibodies were detected in almost all patients but there were no differences in titers and positive rate between TBII-negative and -positive groups. Conclusion: Although TBII-negative Graves patients showed less weight loss and low 99mTc04 thyroidal uptake compare to TBII-positive patients, the clinical and immunological characteristics of TBII-negative patients are not different from TBII-positive one.
Changes in Serum Lipids and Apolipoproteins Levels According to the Thyroxine Treatment in The Patients with Subclinical Hypothyroidism.
Hye Young Park, Bo Youn Cho, Won Bae Kim, Hong Gyu Lee, Chang Soon Koh, Geon Sang Park, Hyung Kyu Park, Sook Kyung Kim, Chan Soo Shin, Seong Yeon Kim
J Korean Endocr Soc. 1996;11(1):41-51.   Published online November 7, 2019
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Background
Subclinical hypothyroidism(SCH) is a common biochemical abnormality which can be found in routine screening tests of thyroid function. We are increasingly faced with the question of whether its an indication for thyroxine replacement therapy. The effect of thyroxine replacement on lipid profile in SCH has aroused a great interest because of an association of overt hypothyroidism(OVH) with hyperlipidemia and increased risk of coronary artery disease. Method: We prospectively evaluated the changes in lipids and apoproteins before and after thyroxine replacement therapy in 23 patients with SCH and in 37 patients with OVH. We measured serum total cholesterol and triglyceride using autoanalyzer, high density lipoprotein(HDL) chole-sterol by dextran sulfate method, Apo A1 and Apo B by immunonephelometric assay. Results: Thyroxine replacement therapy significantly decreased total cholesterol, low density lipoprotein(LDL) cholesterol and apo B levels, but did not affect the level of triglyceride, HDL cholesterol or apo AI in patients with OVH. In SCH, thyroxine replacement therapy with the doses to normalize serum TSH concentrations also decreased significantly the level of cholesterol and LDL cholesterol albeit apo B levels did not change. Moreover, in most of patients with OVH (11 of 12) and in all of patients with SCH(5 of 5) who had had hyperchlesterolemia before treatment, thyroxine replament normalized their cholesterol and LDL cholesterol levels. Conclusion: In regard to the beneficial changes in blood lipid levels, patients with SCH should be treated, especially in cases who have other risk factors for the development of atherosclerosis. If thyroxine replacement only will reduce the incidence of coronary artery disease in SCH remains to be elucidated by long-term prospective studies.
Difference of Thyroid Stimulating Antidody Activities Measured in Chinese Hamster Ovary Cells Stably Transfected with Human TSH Receptor and in FRTL-5 Cells in Graves Disease and Its Clinical Correlations.
Young Kee Shong Young Kee Shong, Hye Young Park, Bo Youn Cho, Won Bae Kim, Hong Gyu Lee, Chang Soon Koh, Yeon Sang Oh
J Korean Endocr Soc. 1996;11(1):18-29.   Published online November 7, 2019
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Background
: Thyroid stimulating antibodies result in the development of hyperthyroidism and goiter in Graves disease. However, thyroid stimulating antibody activities do not correlate with the clinical features in many patients with Graves disease. The purpose of this study is to address this discrepancy between thyroid stimulating antibody activities and clinical features of Graves patients. Methods: We measured thyroid stimulating antibody activities simultaneously using human TSH receptor transfected Chinese hamster(hTSHR-CHO) cells and rat thyroid(FRTL-5) cells in 57 untreated patients with Graves disease, and compared their activities with clinical features including thyroid hormone levels. Results : The detection rate of thyroid stimulating antibody measured by hTSHR-CHO cells was 90% in 57 untreated Graves patients and it was higher than that measured by FRTL-5 cells. Thyroid stimulating antibody activity by hTSHR-CHO cells was significantly correlated with that by FRTL-5 cells(r=0.5, p<0.001), however, 18 of 57(32%) patients showed marked discrepancy of thyroid stimulating antibody activity between in hTSHR-CHO and FRTL-5 systems. Thyroid stimulating antibody activity measured by hTSHR-CHO cells was significantly correlated with serum total T3, free T4 levels, and goiter size but not 99mTc-thyroid uptake. On the other hand, thyroid stimulating antibody activity measured by FRTL-5 cells was significantly correlated with goiter size and 99mTc-thyroid uptake but not thyroid hormone levels. The difference between function and goiter size with respect to thyroid stimulating antibody measurement in two cells system is, nevertheless, particularly evident in the free T4/goiter ratio in patients with high hTSHR-CHO and low FRTL-5 cell assay values. Conclusion: These findings suggest that thyroid stimulating antibodies in Graves disease are heterogeneous population in terms of responses to different origin of cells. Further, thyroid stimulating antibody activities measured by FRTL-5 cells tend to correlate better with goiter size and Tc-thyroid uptake, whereas thyroid stimulating antibody activities measured by hTSH-CHO cells correlate better with thyroid hormone levels.
Assay of Thyrotropin Receptor Antibodies with Recombinant Human Thyrotropin Receptor Expressed on Chinese Hamster Ovary Cells.
Bo Youn Cho, Hong Kyu Lee, Chang Soon Koh, Jae Hoon Chung, Ka Hee Yi, Kyung Soo Ko, Won Bae Kim
J Korean Endocr Soc. 1995;10(4):347-361.   Published online November 7, 2019
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Thyroid stimulating antibody which results in the development of hyperthyroidism and goiter in Graves' patients used to be measured by using rat thyroid cells, FRTL-5. However, this assay has disadvantages: decreased sensitivity due to differences in species, and fastidious culture conditions for FRTL-5 cells. Thus, we recently created stably transfected Chinese hamster ovary(CHO) cells containing the human TSH receptor(hTSHR-CHO) and developed optimal conditions for the measurement of thyroid stimulating antibody using hTSHR-CHO cells. In this study, to evaluate the clinical relevance of thyroid stimulating antibody measurement using hTSHR-CHO cells, we measured thyroid stimulating antibody activities of IgGs from Graves' disease and other thyroid disease using hTSHR-CHO cells, and compared to those of thyroid stimulating antibody assays using FRTL-5 cells. 1) The cut off value of positive thyroid stimulating antibody activity measured in hTSHR-CHO cells was 145%(above the mean +2SD) which was lower than 165% in FRTL-5 cells. The intra-assay and inter-assay variances were 3.9% to 9.0% and 12.7% to 1.6%, respectively. 2) Thyroid stimulating antibody activity was detected in 90% of patients with untreated Graves' disease when patients initially presented. Further, in patients seen initially but already under therapy, 75% had positive values if they were hyperthyroid but only 43% had IgGs with activity if they were euthyroid. Patients in clinical remission after therapy showed positive values in 23% of cases. Only 2 of 25 patients with Hashimoto's thyroiditis showed weak thyroid stimulating antibody activity, none of 18 patients with nodular nontoxie goiter, 1 of 15 patients with primary myxedema, and 2 of 33 control patients with no thyroid disease. Thus, the detection frequency and specificity of the assay with hTSHR-CHO cells was excellent for this type bioassay.3) The detection frequency of thyroid stimulating antibody activity by hTSHR-CHO cells assay system(90%) was higher than that by FRTL-5 cells assay system(66%) in untreated Graves' patients. Those two activities were positively correlated with each other(r=0.52, p<0.001). However, some IgGs showed discrepancy of the thyroid stimulating antibody activity measured in hTSHR-CHO cells and in FRTL-5 cells; 56 of 87 patients were positive in both cells system, 8 of 87 were negative in both cells system, 1 of 87 was only positive in FRTL-5 cells and 22 of 87 were only positive in hTSHR-CHO cell system. Thus, 73%(22/30) of IgGs showing negative values of thyroid stimulating antibody activities in FRTL-5 cells were detected its activities in hTSHR-CHO cells system.In summary, thyroid stimulating antibody assay with hTSHR-CHO cells exhibited so excellent sensitivity and specificity that this technique should be used for clinical practice as well as basic research.
Thyroid Stimulating Antibody Assay with Chinese Hamster Ovary Cells Expressing Human Thyroid Stimulating Hormone (TSH) Receptor; Optimization of Assay Condition.
Bo Youn Cho, Hong Kyu Lee, Young Kee Shong, Chang Soon Koh, Ka Hee Yi, Yeon Sahng Oh, Won Bae Kim
J Korean Endocr Soc. 1995;10(4):333-346.   Published online November 7, 2019
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We investigated the optimal condition of thyroid stimulating antibody(TSAb) assay using Chinese hamster ovary cells transfected with cDNA of human TSH receptor(TSHr-CHO) stably expressing functional TSH receptors. The extracellular cAMP responses of TSHr-CHO cells to the stimulation of bTSH or Graves' IgG were observed in three different incubation media. Stimulation indices of extracellular cAMP were higher when sucrose containing NaCl-free isotonic Hank's balanced salt solution(HBSS)(media A)was used as incubation media than those of NaCl-free hypotonic HBSS(media B) or those of NaCl containing isotonic HBSS(media C). The incubation of TSHr-CHO cells in media B caused marked increase in the basal cAMP level without concomittant fold-increase in the stimulated cAMP level at various doses of bTSH and Graves' IgG. Decreasing the stimulation indices of extracellular cAMP, use of media B failed to detect TSAb activities in two TSAb-positive Graves' IgG tested. In case of media C, extracellular cAMP responses are poor at 0.001 and 0.1U/L of bTSH and at all doses of Graves' IgG tested(0.5, 1, 5g/L). The incubation of TSHr-CHO cells in media B caused significant increase in the number of trypan blue-stained, nonviable cells(5.7+-1.5, 7.6+-1.9 and 8.5+-1.6% at 1, 2 and 3h of incubation, respectively; p<0.01) comparing to those incubated in media A or media C(about 2-3% in both media). Those decrease in the viability of TSHr-CHO cells when incubated in hypotonic incubation media may explain the decrease in the stimulation index of extracellular cAMP with the use of media B in contrast to the case of FRTL-5 cells. TSAb assay of 87 consecutive fresh Graves' patients with TSHr-CHO cells using media A detected TSAb activities in 90%(78 patients) of them, and moreover TSAb activities showed significant positive correlation with the pre-treatment serum T_3 and free T_4 levels of those patients. We conclude that TSAb assay with TSHr-CHO cells is a sensitive and physiologically relevant assay system to measure TSAb activities merely through measurements of extracellular cAMP provided that the cells are incubated in NaCl-free isotonic incubation media.
Changes in Thyrotropin Receptor Blocking Antibody after Antithyroid drug Administration to Patients with Atrophic Autoimmune Thyroiditis (Primary Myxedema).
Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee, Jae Hoon Chung, Chang Soon Koh, Chan Soo Shin, Won Bae Kim
J Korean Endocr Soc. 1994;10(3):229-241.   Published online November 6, 2019
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It is well Known that antithyroid drug treatment of Graves' disease suppresses excessive thyroid hormone synthesis and causes a parallel decrease in serum thyroid autoantibody levels including thyroid stimulating antibodies(TSAb) in most patients suggesting the immunosuppressive or immunomodulating effects of antithyroid drugs. In the context of view that thyrotropin receptor blocking antibody may play an important pathogenetic role at least in some patients with primary myxedema(chronic atrophic autoimmune thyroiditis), antithyroid drug treatment in these patients might be beneficial to disease course. To evaluate the effect of antithyroid drug on the thyrotropin receptor blocking antibody levels, we serially measured thyrotropin-binding inhibitor immunoglobulins(TBII) and thyroid stimulation blocking antibodies(TSBAb) using FRTL-5 cells, antimicrosomal- and antithyroglobulin antibody activities in 7 patients with primary myedema who have blocking TSH receptor antibodies during 6 months of methimazole(MMI, 40mg/day) administration. TBII and TSBAb activities did not change after MMI, but one of them showed stepwise decrease and disappearance of TBII and TSBAb activities. Antimicrosomal- and antithyroglobulin antibody activities decreased significantly after 3 months of MMI administration in those patients. These results suggest a minimal effect of antithyroid drug treatment on the level of thyrotropin receptor blocking antibodies. Persistence of thyrotropin receptor blocking antibodies despite of the decrease in antimicrosomal and antithyroglobulin antibodies might suggest that blocking TSH receptor antibodies of primary myxedema is produced mainly in extrathyroidal tissue in contrast to the thyroid stimulating antibodies of Graves' disease. One patient, whose blocking antibody have disappeared after MMI treatment, is under observation to see if she will remain in remission of hypothyroidism.
Evaluation of the Usefulness of Free T4 Measured by 2 - Step Iimmunoextraction in the Patients with Thyroid and Non - Thyroid Diseases.
Bo Youn Cho, Hong Kyu Lee, Jae Hoon Chung, Seok In Lee, Won Bae Kim, Chang Soon Koh
J Korean Endocr Soc. 1994;10(2):98-104.   Published online November 6, 2019
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Many methods and commercial kits have become available for directly measuring free thyroxine(free T_4). However, most of them are inadequate for routine laboratory use because of their complexity and inaccuracy. Recently, 2-step RIA methods by immunoextraction(2-step immunoextraction) for free T_4 have been developed to improve its accuracy and convenience. We evaluated the usefulness of free T_4 measured by 2-step immunoextraction compared to free T_4 index(FT_4I), free T_4 measured by 1-step RIA, and TSH in 204 patients with thyroid and non-thyroid disease. There were no differences in sensitivities and specificities of free T_4(1-step, 2-step), FT_4I and TSH in the patients with hyperthyroidism and euthyroid nodule. However, the sensitivity of TSH in hypothyroidism was remarkablely higher than the others(100.0% vs. 61.5-81.5%). The sensitivity of free T_4(2-step) was also higher than those of free T_4(1-step), FT_4I and TSH in the patients with non-thyroid disease(94.3% vs. 74.3-83.8%). The values of free T_4 measured by 1-step RIA were significantly lower than those by 2-step immunoextraction, especially in the patients with non-thyroid disease(1.10+-0.04 vs. 1.55+-0.03ng/dL, p<0.05).In conclusion, no significant differences were found in sensitivity and specificity of free T_4(1-step, 2-step), FT_4I, and TSH in the patients with thyroid diseases except in hypothyroidism. However, the sensitivity of free T_4 measured by 2-step immunoextraction was significantly higher than the other tests, especially in the patients with non-thyroid disease. Therefore, free T_4 assay using 2-step immunoextraction is useful to differentiate the non-thyroid disease from thyroid diseases.
A Case of Thyroid Anaplastic Cancer with Intestinal Metastasis.
Seong Yeon Kim, Kyung Soo Park, Bo Youn Cho, Hong Kyu Lee, Chang Soon Koh, Jae Seok Jeon, Min Seon Kim, Won Bae Kim
J Korean Endocr Soc. 1994;9(4):375-379.   Published online November 6, 2019
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Thyroid anaplastic cancer is one of the most malignant neoplasms encountered in human. These tumors usually present as rapidly enlarging neck mass in old patients who may or may not have had a previously recognized goiter. The distant metastases of anaplastic cancer eventually occur in about 50% patients, mostly in the lung and bone and are an important prognostic factor, substantially reducing survival time.A 66-year old man visited out hospital because of rapidly growing anterior neck mass and hoarseness. He was diagnosed as thyroid anaplastic cancer with lymph node and lung metastasis and received combined chemotherapy and radiation therapy. On the 8th hospital day, severe abdominal pain developed and exploratory laparotomy was conducted. During operation, two intestinal mass were discovered, one of which was perforated. The microscopic examinations showed that undifferentiated malignant cells were infiltrated in the wall of small bowel. We report this case because we first experienced thyroid anaplastic cancer with intestinal metastasis.
Changes of blood pressure and RBC membrane Na+ transport in thyroid disease.
Won Bae Kim, Kyung Soo Ko, Suk In Lee, Seong Yeon Kim, Bo Yeon Cho, Hong Kyu Lee, Chang Soon Koh, Hun Ki Min
J Korean Endocr Soc. 1991;6(1):25-37.   Published online January 1, 2001
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AbstractAbstract PDF
No abstract available.

Endocrinol Metab : Endocrinology and Metabolism