Endocrinology and Metabolism

Original Article

Thyroid
Long-Term Changes in the Mortality Rates of Thyroid Cancer in Korea: Analysis of Korean National Data from 1985 to 2020: Yun Mi Choi, Min-Ju Kim, Jiwoo Lee, Mi Kyung Kwak, Min Ji Jeon, Tae Yong Kim, Eun-Gyoung Hong, Won Bae Kim, Won Gu Kim; Endocrinol Metab. 2023;38(5):588-595. Published online September 8, 2023; DOI: https://doi.org/10.3803/EnM.2023.1723

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Abstract PDF Supplementary Material PubReader ePub: Background
Thyroid cancer mortality has been largely overlooked as relatively stable given the large gap between thyroid cancer incidence and mortality. This study evaluated long-term trends in age-standardized mortality rates (ASMRs) throughout Korea and compared them with mortality data reported by the Surveillance, Epidemiology, and End Results (SEER).
Methods
Cancer-specific mortality data from 1985 to 2020 were obtained from Statistics Korea. ASMRs from thyroid cancer were calculated based on the Korean mid-year resident registration population of 2005. We assessed SEER*Explorer and downloaded the mortality data.
Results
The ASMR increased from 0.19 to 0.77/100,000 between 1985 and 2002 but decreased continuously to 0.36/100,000 in 2020. The annual percent change (APC) in the ASMR between 1985 and 2003 and between 2003 and 2020 was 6.204 and −4.218, respectively, with similar patterns observed in both men and women. The ASMR of the SEER showed a modest increase from 1988 to 2016 and then stabilized. In subgroup analysis, the ASMR of the old age group (≥55 years) increased significantly from 0.82 in 1985 to 3.92/100,000 in 2002 (APC 6.917) but then decreased again to 1.86/100,000 in 2020 (APC −4.136). ASMRs according to the age group in the SEER showed a relatively stable trend even in the elderly group.
Conclusion
The ASMR of thyroid cancer in Korea had increased from 1985 to 2002 but has since been steadily decreasing. This trend was mainly attributed to elderly people aged 55 or over. The absolute APC value of Korea was much higher than that of the SEER.

Review Article

Thyroid
Preclinical Models of Follicular Cell-Derived Thyroid Cancer: An Overview from Cancer Cell Lines to Mouse Models: Min Ji Jeon, Bryan R. Haugen; Endocrinol Metab. 2022;37(6):830-838. Published online December 26, 2022; DOI: https://doi.org/10.3803/EnM.2022.1636

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The overall prognosis of thyroid cancer is excellent, but some patients have grossly invasive disease and distant metastases with limited responses to systemic therapies. Thus, relevant preclinical models are needed to investigate thyroid cancer biology and novel treatments. Different preclinical models have recently emerged with advances in thyroid cancer genetics, mouse modeling and new cell lines. Choosing the appropriate model according to the research question is crucial to studying thyroid cancer. This review will discuss the current preclinical models frequently used in thyroid cancer research, from cell lines to mouse models, and future perspectives on patient-derived and humanized preclinical models in this field.

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Mouse Models to Examine Differentiated Thyroid Cancer Pathogenesis: Recent Updates
Hye Choi, Kwangsoon Kim
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Modeling the tumor microenvironment of anaplastic thyroid cancer: an orthotopic tumor model in C57BL/6 mice
Zhen Xu, Hyo Shik Shin, Yoo Hyung Kim, Seong Yun Ha, Jae-Kyung Won, Su-jin Kim, Young Joo Park, Sareh Parangi, Sun Wook Cho, Kyu Eun Lee
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Patient-derived tumor models: a suitable tool for preclinical studies on esophageal cancer
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Original 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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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.

Citations

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Cancer and Mortality Risks of Graves’ Disease in South Korea Based on National Data from 2010 to 2019
Young Ju Choi, Kyungdo Han, Won Kyoung Cho, Min Ho Jung, Byung-Kyu Suh
Clinical Epidemiology.2023; Volume 15: 535. CrossRef
Survival Comparison of Incidentally Found versus Clinically Detected Thyroid Cancers: An Analysis of a Nationwide Cohort Study
Shinje Moon, Eun Kyung Lee, Hoonsung Choi, Sue K. Park, Young Joo Park
Endocrinology and Metabolism.2023; 38(1): 81. CrossRef
Cumulative exposure to metabolic syndrome increases thyroid cancer risk in young adults: a population-based cohort study
Jinyoung Kim, Kyungdo Han, Mee Kyoung Kim, Ki-Hyun Baek, Ki-Ho Song, Hyuk-Sang Kwon
The Korean Journal of Internal Medicine.2023; 38(4): 526. CrossRef
Cost-Effectiveness of Active Surveillance Compared to Early Surgery of Small Papillary Thyroid Cancer: A Retrospective Study on a Korean Population
Han-Sang Baek, Jeonghoon Ha, Kwangsoon Kim, Jaseong Bae, Jeong Soo Kim, Sungju Kim, Dong-Jun Lim, Chulmin Kim
Journal of Korean Medical Science.2023;[Epub] CrossRef
Long-Term Changes in the Mortality Rates of Thyroid Cancer in Korea: Analysis of Korean National Data from 1985 to 2020
Yun Mi Choi, Min-Ju Kim, Jiwoo Lee, Mi Kyung Kwak, Min Ji Jeon, Tae Yong Kim, Eun-Gyoung Hong, Won Bae Kim, Won Gu Kim
Endocrinology and Metabolism.2023; 38(5): 588. CrossRef
Age and Post-Lobectomy Recurrence after Endoscopic or Robotic Thyroid Surgery: A Retrospective Cohort Study of 2348 Papillary Thyroid Carcinoma Patients
Jin-Seong Cho, Yong-Min Na, Hee Kyung Kim
Cancers.2023; 15(23): 5506. CrossRef

Thyroid
Immunoglobulin G4-Related Thyroid Disease: A Single-Center Experience and Literature Review: Meihua Jin, Bictdeun Kim, Ahreum Jang, Min Ji Jeon, Young Jun Choi, Yu-Mi Lee, Dong Eun Song, Won Gu Kim; Endocrinol Metab. 2022;37(2):312-322. Published online April 25, 2022; DOI: https://doi.org/10.3803/EnM.2021.1318

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Background
Immunoglobulin G4 (IgG4)-related disease is an entity that can involve the thyroid gland. The spectrum of IgG4-related thyroid disease (IgG4-RTD) includes Hashimoto thyroiditis (HT) and its fibrotic variant, Riedel thyroiditis, as well as Graves’ disease. The early diagnosis of IgG4-RTD is important because it is a medically treatable disease, and a delay in the diagnosis might result in unnecessary surgery. We present a case series of IgG4-RTD with a review of the literature.
Methods
We retrospectively reviewed the clinical presentation and the radiological and pathological findings of patients diagnosed with IgG4-RTD between 2017 and 2021 at a tertiary medical center in Korea. We also conducted a literature review of IgG4-RTD.
Results
Five patients were diagnosed with IgG4-RTD during the study period. The patients’ age ranged from 31 to 76 years, and three patients were men. Most patients visited the clinic for a neck mass, and hypoechogenic nodular lesions were observed on neck ultrasonography. Three patients had IgG4 HT, and two patients had IgG4 Riedel thyroiditis. All patients developed hypothyroidism that necessitated L-thyroxine replacement. The diagnosis of IgG4-RTD was confirmed after a pathological examination of the surgical specimen in the first two cases. However, the early diagnosis was possible after a core needle biopsy in three clinically suspected patients.
Conclusion
The diagnosis of IgG4-RTD requires clinical suspicion combined with serology and histological analyses using IgG4 immunostaining. The early diagnosis of IgG4-RTD is difficult; thus, biopsy with IgG4 immunostaining and serum IgG4 measurements will help diagnose patients suspected of having IgG4-RTD.

Citations

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Reshaping the Concept of Riedel’s Thyroiditis into the Larger Frame of IgG4-Related Disease (Spectrum of IgG4-Related Thyroid Disease)
Mara Carsote, Claudiu Nistor
Biomedicines.2023; 11(6): 1691. CrossRef

Corrigenda

Miscellaneous
Corrigendum: Correction of Acknowledgments. 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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Risk of thyroid cancer associated with glucagon‐like peptide‐1 receptor agonists and dipeptidyl peptidase‐4 inhibitors in patients with type 2 diabetes: A population‐based cohort study
Sungho Bea, Heejun Son, Jae Hyun Bae, Sun Wook Cho, Ju‐Young Shin, Young Min Cho
Diabetes, Obesity and Metabolism.2023;[Epub] CrossRef

Miscellaneous
Corrigendum: Correction of Acknowledgments. 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. 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

Original Articles

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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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.

Citations

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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
Cancer and Mortality Risks of Graves’ Disease in South Korea Based on National Data from 2010 to 2019
Young Ju Choi, Kyungdo Han, Won Kyoung Cho, Min Ho Jung, Byung-Kyu Suh
Clinical Epidemiology.2023; Volume 15: 535. CrossRef
Risk and Prognosis of Thyroid Cancer in Patients with Graves’ Disease: An Umbrella Review
Marco Palella, Francesca Maria Giustolisi, Adriana Modica Fiascaro, Martina Fichera, Antonella Palmieri, Rossella Cannarella, Aldo E. Calogero, Margherita Ferrante, Maria Fiore
Cancers.2023; 15(10): 2724. CrossRef
Characteristics, staging and outcomes of differentiated thyroid cancer in patients with and without Graves’ disease
Chaitra Gopinath, Hanna Crow, Sujata Panthi, Leonidas Bantis, Kenneth D. Burman, Chitra Choudhary
Journal of Clinical & Translational Endocrinology.2023; 33: 100321. CrossRef
Prevalence, Treatment Status, and Comorbidities of Hyperthyroidism in Korea from 2003 to 2018: A Nationwide Population Study
Hwa Young Ahn, Sun Wook Cho, Mi Young Lee, Young Joo Park, Bon Seok Koo, Hang-Seok Chang, Ka Hee Yi
Endocrinology and Metabolism.2023; 38(4): 436. CrossRef
Hashimoto’s Thyroiditis and Papillary Thyroid Carcinoma: A Follow-Up Study in Patients with Absence of Aggressive Risk Factors at the Surgery of the Primary Tumor
Andrea Marongiu, Susanna Nuvoli, Andrea De Vito, Sonia Vargiu, Angela Spanu, Giuseppe Madeddu
Diagnostics.2023; 13(19): 3068. 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
An unusual case of papillary thyroid carcinoma presenting as Graves’ disease
Pooja Tiwari, Uma Kaimal Saikia, Abhamoni Baro, Ashok Krishna Bhuyan
Thyroid Research and Practice.2022; 19(1): 47. 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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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

Review Article

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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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; 81(2): 290. 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

Original Articles

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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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.

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Some genetic differences in patients with rheumatoid arthritis
Hosam M. Ahmad, Zaki M. Zaki, Asmaa S. Mohamed, Amr E. Ahmed
BMC Research Notes.2023;[Epub] CrossRef
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
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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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.

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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
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Mitsuyoshi Hirokawa, Manon Auger, Chan Kwon Jung, Fabiano Mesquita Callegari
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Thyroid®.2023; 33(10): 1182. CrossRef
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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
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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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

Citations to this article as recorded by

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
Dynamic risk assessment in patients with differentiated thyroid cancer
Erika Abelleira, Fernando Jerkovich
Reviews in Endocrine and Metabolic Disorders.2023;[Epub] 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 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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109 Download
6 Citations

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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

Citations to this article as recorded by

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
TERT Promoter Mutation as a Prognostic Marker in Encapsulated Angioinvasive and Widely Invasive Follicular Thyroid Carcinomas
Yasuhiro Ito, Takashi Akamizu
Clinical Thyroidology.2023; 35(5): 202. CrossRef
Risk factors for death of follicular thyroid carcinoma: a systematic review and meta-analysis
Ting Zhang, Liang He, Zhihong Wang, Wenwu Dong, Wei Sun, Ping Zhang, Hao Zhang
Endocrine.2023; 82(3): 457. 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
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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Abstract PDF PubReader ePub: 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
Vandetanib for the Management of Advanced Medullary Thyroid Cancer: A Real-World Multicenter Experience: Mijin Kim, Jee Hee Yoon, Jonghwa Ahn, Min Ji Jeon, Hee Kyung Kim, Dong Jun Lim, Ho-Cheol Kang, In Joo Kim, Young Kee Shong, Tae Yong Kim, Bo Hyun Kim; Endocrinol Metab. 2020;35(3):587-594. Published online September 22, 2020; DOI: https://doi.org/10.3803/EnM.2020.687

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Background
Vandetanib is the most widely used tyrosine kinase inhibitor for the treatment of patients with advanced medullary thyroid cancer (MTC). However, only limited data regarding its use outside clinical trials are available. We aimed to evaluate the efficacy and safety of vandetanib in patients with advanced MTC in routine clinical practice.
Methods
In this multicenter retrospective study, 12 patients with locally advanced or metastatic MTC treated with vandetanib at four tertiary hospitals were included. The primary outcome was the objective response rate (ORR) based on the Response Evaluation Criteria in Solid Tumors. The progression-free survival (PFS), overall survival (OS), and toxicities were also evaluated.
Results
Eleven patients (92%) had distant metastasis and 10 (83%) had disease progression at enrollment. Partial response was observed in five patients (ORR, 42%) and stable disease lasting ≥24 weeks was reported in an additional five patients (83%). During the median 31.7 months of follow-up, disease progression was seen in five patients (42%); of these, two died due to disease progression. The median PFS was 25.9 months, while the median OS was not reached. All patients experienced adverse events (AEs) which were generally consistent with the known safety profile of vandetanib. Vandetanib was discontinued in two patients due to skin toxicity.
Conclusion
Consistent with the phase III trial, this study confirmed the efficacy of vandetanib for advanced MTC in terms of both ORR and PFS in the real-world setting. Vandetanib was well tolerated in the majority of patients, and there were no fatal AEs.

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Metastatic medullary thyroid carcinoma (MTC): disease course, treatment modalities and factors predisposing for drug resistance
Katerina Saltiki, George Simeakis, Olga Karapanou, Stavroula A. Paschou, Maria Alevizaki
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Initial Experiences of Selective RET Inhibitor Selpercatinib in Adults with Metastatic Differentiated Thyroid Carcinoma and Medullary Thyroid Carcinoma: Real-World Case Series in Korea
Han-Sang Baek, Jeonghoon Ha, Seunggyun Ha, Ja Seong Bae, Chan Kwon Jung, Dong-Jun Lim
Current Oncology.2023; 30(3): 3020. CrossRef
Molecular Basis and Natural History of Medullary Thyroid Cancer: It is (Almost) All in the RET
Nicolas Sahakian, Frédéric Castinetti, Pauline Romanet
Cancers.2023; 15(19): 4865. CrossRef
Sporadic Medullary Thyroid Carcinoma: Towards a Precision Medicine
Antonio Matrone, Carla Gambale, Alessandro Prete, Rossella Elisei
Frontiers in Endocrinology.2022;[Epub] CrossRef
Targeted therapy and drug resistance in thyroid cancer
Yujie Zhang, Zhichao Xing, Tianyou Liu, Minghai Tang, Li Mi, Jingqiang Zhu, Wenshuang Wu, Tao Wei
European Journal of Medicinal Chemistry.2022; 238: 114500. CrossRef
Daily Management of Patients on Multikinase Inhibitors’ Treatment
Carla Colombo, Simone De Leo, Matteo Trevisan, Noemi Giancola, Anna Scaltrito, Laura Fugazzola
Frontiers in Oncology.2022;[Epub] CrossRef
The Angiogenic Balance and Its Implications in Cancer and Cardiovascular Diseases: An Overview
Cătălina Ionescu, Bogdan Oprea, Georgeta Ciobanu, Milena Georgescu, Ramona Bică, Garofiţa-Olivia Mateescu, Fidan Huseynova, Veronique Barragan-Montero
Medicina.2022; 58(7): 903. CrossRef
Reassessing vascular endothelial growth factor (VEGF) in anti-angiogenic cancer therapy
Tobiloba C. Elebiyo, Damilare Rotimi, Ikponmwosa O. Evbuomwan, Rotdelmwa Filibus Maimako, Matthew Iyobhebhe, Oluwafemi Adeleke Ojo, Olarewaju M. Oluba, Oluyomi S. Adeyemi
Cancer Treatment and Research Communications.2022; 32: 100620. CrossRef
Current Guidelines for Management of Medullary Thyroid Carcinoma
Mijin Kim, Bo Hyun Kim
Endocrinology and Metabolism.2021; 36(3): 514. CrossRef
Recent advances in precision medicine for the treatment of medullary thyroid cancer
Jolanta Krajewska, Aleksandra Kukulska, Malgorzata Oczko-Wojciechowska, Barbara Jarzab
Expert Review of Precision Medicine and Drug Development.2021; 6(5): 307. CrossRef
Functional evaluation of vandetanib metabolism by CYP3A4 variants and potential drug interactions in vitro
Mingming Han, Xiaodan Zhang, Zhize Ye, Jing Wang, Jianchang Qian, Guoxin Hu, Jianping Cai
Chemico-Biological Interactions.2021; 350: 109700. CrossRef
Nephrotoxicity in advanced thyroid cancer treated with tyrosine kinase inhibitors: An update
Alice Nervo, Francesca Retta, Alberto Ragni, Alessandro Piovesan, Alberto Mella, Luigi Biancone, Marco Manganaro, Marco Gallo, Emanuela Arvat
Critical Reviews in Oncology/Hematology.2021; 168: 103533. CrossRef

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