Endocrinology and Metabolism

Corrigendum

Thyroid
Corrigendum: Abstract and Text Correction. 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. 2023;38(3):357. Published online May 16, 2023; DOI: https://doi.org/10.3803/EnM.2023.301; Corrects: Endocrinol Metab 2017;32(1):106

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Original Articles

Thyroid
Identification of Mutations in the Thyroxine-Binding Globulin (TBG) Gene in Patients with TBG Deficiency in Korea: Jung Heo, Sang-Mi Kim, Hyun Jin Ryu, Hyunju Park, Tae Hyuk Kim, Jae Hoon Chung, Hyung-Doo Park, Sun Wook Kim; Endocrinol Metab. 2022;37(6):870-878. Published online December 7, 2022; DOI: https://doi.org/10.3803/EnM.2022.1591

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Background
Thyroxine-binding globulin (TBG) is a major transporter protein for thyroid hormones. The serpin family A member 7 (SERPINA7) gene codes for TBG, and mutations of the SERPINA7 gene result in TBG deficiency. Although more than 40 mutations have been reported in several countries, only a few studies of TBG deficiency and SERPINA7 gene mutation have been performed in Korea. The aim of this study is to review the clinical presentations and laboratory findings of patients with TBG deficiency and to investigate the types of SERPINA7 gene mutation.
Methods
Five unrelated Korean adults with TBG deficiency attending endocrinology clinic underwent SERPINA7 gene sequencing. Four patients harbored a SERPINA7 gene mutation. Serum thyroid hormones, anti-microsomal antibodies, and TBG were measured. Genomic DNA was extracted from whole blood. All exons and intron-exon boundaries of the TBG gene were amplified and sequencing was performed.
Results
Two patients were heterozygous females, and the other two were hemizygous males. One heterozygous female had coexisting hypothyroidism. The other heterozygous female was erroneously prescribed levothyroxine at a local clinic. One hemizygous male harbored a novel mutation, p.Phe269Cysfs*18, which caused TBG partial deficiency. Three patients had the p.Leu372Phefs*23 mutation, which is known as TBG-complete deficiency Japan (TBG-CDJ) and was also presented in previous mutation analyses in Korea.
Conclusion
This study presents four patients diagnosed with TBG deficiency and provides the results of SERPINA7 gene sequencing. One novel mutation, p.Phe269Cysfs*18, causing TBD-partial deficiency and three cases of TBG-CDJ were demonstrated. It is necessary to identify TBG deficiency to prevent improper treatment. Also, sequencing of the SERPINA7 gene would provide valuable information about the TBG variants in Korea.

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Development and basic performance verification of a rapid homogeneous bioassay for agonistic antibodies against the thyroid-stimulating hormone receptor
Motoki Hoshina, Shiomi Ojima, Atsushi Kawasaki, Kosuke Doi, Satoshi Ohta, Asuka Inoue, Hiroshi Murayama
Journal of Immunological Methods.2024; 528: 113655. CrossRef

Thyroid
Frequency of TERT Promoter Mutations in Real-World Analysis of 2,092 Thyroid Carcinoma Patients: Heera Yang, Hyunju Park, Hyun Jin Ryu, Jung Heo, Jung-Sun Kim, Young Lyun Oh, Jun-Ho Choe, Jung Han Kim, Jee Soo Kim, Hye Won Jang, Tae Hyuk Kim, Sun Wook Kim, Jae Hoon Chung; Endocrinol Metab. 2022;37(4):652-663. Published online July 22, 2022; DOI: https://doi.org/10.3803/EnM.2022.1477

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Background
Telomerase reverse transcriptase (TERT) promoter mutations are associated with increased recurrence and mortality in patients with thyroid carcinoma. Previous studies on TERT promoter mutations were retrospectively conducted on a limited number of patients.
Methods
We prospectively collected data on all consecutive patients who underwent thyroid carcinoma surgery between January 2019 and December 2020 at the Samsung Medical Center, Seoul, Korea. We included 2,092 patients with thyroid carcinoma.
Results
Of 2,092 patients, 72 patients (3.4%) had TERT promoter mutations. However, the frequency of TERT promoter mutations was 0.5% in papillary thyroid microcarcinoma (PTMC) ≤1 cm and it was 5.8% in papillary thyroid carcinoma (PTC) >1 cm. The frequency of TERT promoter mutations was significantly associated with older age at diagnosis (odds ratio [OR], 1.12; P<0.001), larger primary tumor size (OR, 2.02; P<0.001), and aggressive histological type (OR, 7.78 in follicular thyroid carcinoma; OR, 10.33 in poorly differentiated thyroid carcinoma; OR, 45.92 in anaplastic thyroid carcinoma; P<0.001). Advanced T stage, advanced N stage, and distant metastasis at diagnosis were highly prevalent in mutated thyroid cancers. However, initial distant metastasis was not present in patients with TERT promoter mutations in PTMC. Although the C228T mutation was more highly detected than the C250T mutation (64 cases vs. 7 cases), there were no significant clinicopathological differences.
Conclusion
This study is the first attempt to investigate the frequency of TERT promoter mutations in a real-world setting. The frequency of TERT promoter mutations in PTC was lower than expected, and in PTMC, young patients, and female patients, the frequency was very low.

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TERT Promoter Mutations Frequency Across Race, Sex, and Cancer Type
Talal El Zarif, Marc Machaalani, Rashad Nawfal, Amin H Nassar, Wanling Xie, Toni K Choueiri, Mark Pomerantz
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Gene mutations as predictors of central lymph mode metastasis in cN0 PTC: A meta‐analysis
Jiaqi Ji, Xinlong Shi
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Risk stratification by combining common genetic mutations and TERT promoter methylation in papillary thyroid cancer
Ye Sang, Guanghui Hu, Junyu Xue, Mengke Chen, Shubin Hong, Rengyun Liu
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International Journal of Thyroidology.2023; 16(1): 1. CrossRef
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Jae Hoon Chung
International Journal of Thyroidology.2023; 16(1): 89. CrossRef
Mortality rate and causes of death in papillary thyroid microcarcinoma
Jung Heo, Hyun Jin Ryu, Hyunju Park, Tae Hyuk Kim, Sun Wook Kim, Young Lyun Oh, Jae Hoon Chung
Endocrine.2023; 83(3): 671. CrossRef
TERT promoter mutations in thyroid cancer
Michiko Matsuse, Norisato Mitsutake
Endocrine Journal.2023; 70(11): 1035. CrossRef
TERT Promoter and BRAF V600E Mutations in Papillary Thyroid Cancer: A Single-Institution Experience in Korea
Min Jhi Kim, Jin Kyong Kim, Gi Jeong Kim, Sang-Wook Kang, Jandee Lee, Jong Ju Jeong, Woong Youn Chung, Daham Kim, Kee-Hyun Nam
Cancers.2022; 14(19): 4928. CrossRef
Frequency of TERT Promoter Mutations in Real-World Analysis of 2,092 Thyroid Carcinoma Patients (Endocrinol Metab 2022;37:652-63, Heera Yang et al.)
Hyunju Park, Jae Hoon Chung
Endocrinology and Metabolism.2022; 37(6): 949. CrossRef
Frequency of TERT Promoter Mutations in Real-World Analysis of 2,092 Thyroid Carcinoma Patients (Endocrinol Metab 2022;37:652-63, Heera Yang et al.)
Sue Youn Kim, Chan Kwon Jung
Endocrinology and Metabolism.2022; 37(6): 947. CrossRef

Calcium & Bone Metabolism
Bone Mineral Density Screening Interval and Transition to Osteoporosis in Asian Women: Hyunju Park, Heera Yang, Jung Heo, Hye Won Jang, Jae Hoon Chung, Tae Hyuk Kim, Yong-Ki Min, Sun Wook Kim; Endocrinol Metab. 2022;37(3):506-512. Published online June 9, 2022; DOI: https://doi.org/10.3803/EnM.2022.1429

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Background
Bone mineral density (BMD) testing is indicated for women aged 65 years, but screening strategies for osteoporosis are controversial. Currently, there is no study focusing on the BMD testing interval in Asian populations. The current study aimed to evaluate the estimated time interval for screening osteoporosis.
Methods
We conducted a study of 6,385 subjects aged 50 years and older who underwent dual-energy X-ray absorptiometry screening more than twice at Samsung Medical Center as participants in a routine health checkup. Subjects were divided based on baseline T-score into mild osteopenia (T-score, <–1.0 to >–1.5), moderate osteopenia (T-score, ≤–1.5 to >–2.0), and severe osteopenia (T-score, ≤–2.0 to >–2.5). Information about personal medical and social history was collected by a structured questionnaire.
Results
The adjusted estimated BMD testing interval for 10% of the subjects to develop osteoporosis was 13.2 years in mild osteopenia, 5.0 years in moderate osteopenia, and 1.5 years in severe osteopenia.
Conclusion
Our study provides extended information about BMD screening intervals in Asian female population. Baseline T-score was important for predicting BMD screening interval, and repeat BMD testing within 5 years might not be necessary in mild osteopenia subjects.

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Chaiho Jeong, Jeonghoon Ha, Jun-Il Yoo, Young-Kyun Lee, Jung Hee Kim, Yong-Chan Ha, Yong-Ki Min, Dong-Won Byun, Ki-Hyun Baek, Ho Yeon Chung
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Thyroid Big Data Articles (National Health Insurance Service Database)
Graves’ Disease and the Risk of End-Stage Renal Disease: A Korean Population-Based Study: Yoon Young Cho, Bongseong Kim, Dong Wook Shin, Hye Ryoun Jang, Bo-Yeon Kim, Chan-Hee Jung, Jae Hyeon Kim, Sun Wook Kim, Jae Hoon Chung, Kyungdo Han, Tae Hyuk Kim; Endocrinol Metab. 2022;37(2):281-289. Published online April 6, 2022; DOI: https://doi.org/10.3803/EnM.2021.1333

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Background
Hyperthyroidism is associated with an increased glomerular filtration rate (GFR) in the hyperdynamic state, which is reversible after restoring euthyroidism. However, long-term follow-up of renal dysfunction in patients with hyperthyroidism has not been performed.
Methods
This was a retrospective cohort study using the Korean National Health Insurance database and biannual health checkup data. We included 41,778 Graves’ disease (GD) patients and 41,778 healthy controls, matched by age and sex. The incidences of end-stage renal disease (ESRD) were calculated in GD patients and controls. The cumulative dose and duration of antithyroid drugs (ATDs) were calculated for each patient and categorized into the highest, middle, and lowest tertiles.
Results
Among 41,778 GD patients, 55 ESRD cases occurred during 268,552 person-years of follow-up. Relative to the controls, regardless of smoking, drinking, or comorbidities, including chronic kidney disease, GD patients had a 47% lower risk of developing ESRD (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.37 to 0.76). In particular, GD patients with a higher baseline GFR (≥90 mL/min/1.73 m2; HR, 0.33; 95% CI, 0.11 to 0.99), longer treatment duration (>33 months; HR, 0.31; 95% CI, 0.17 to 0.58) or higher cumulative dose (>16,463 mg; HR, 0.29; 95% CI, 0.15 to 0.57) of ATDs had a significantly reduced risk of ESRD.
Conclusion
This was the first epidemiological study on the effect of GD on ESRD, and we demonstrated that GD population had a reduced risk for developing ESRD.

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Renal function changes in patients with subclinical hyperthyroidism: a novel postulated mechanism
Magdy Mohamed Allam, Hanaa Tarek El-Zawawy, Tarek Hussein El-Zawawy
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Effect of Hyperthyroidism on Preventing Renal Insufficiency
Tae Yong Kim
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Computational and Mathematical Methods in Medicine.2022; 2022: 1. CrossRef

Corrigendum

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.2024; 26(1): 108. CrossRef

Original Articles

Thyroid
A Multicenter, Randomized, Controlled Trial for Assessing the Usefulness of Suppressing Thyroid Stimulating Hormone Target Levels after Thyroid Lobectomy in Low to Intermediate Risk Thyroid Cancer Patients (MASTER): A Study Protocol: Eun Kyung Lee, Yea Eun Kang, Young Joo Park, Bon Seok Koo, Ki-Wook Chung, Eu Jeong Ku, Ho-Ryun Won, Won Sang Yoo, Eonju Jeon, Se Hyun Paek, Yong Sang Lee, Dong Mee Lim, Yong Joon Suh, Ha Kyoung Park, Hyo-Jeong Kim, Bo Hyun Kim, Mijin Kim, Sun Wook Kim, Ka Hee Yi, Sue K. Park, Eun-Jae Jung, June Young Choi, Ja Seong Bae, Joon Hwa Hong, Kee-Hyun Nam, Young Ki Lee, Hyeong Won Yu, Sujeong Go, Young Mi Kang, MASTER study group; Endocrinol Metab. 2021;36(3):574-581. Published online May 26, 2021; DOI: https://doi.org/10.3803/EnM.2020.943

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Background
Postoperative thyroid stimulating hormone (TSH) suppression therapy is recommended for patients with intermediate- and high-risk differentiated thyroid cancer to prevent the recurrence of thyroid cancer. With the recent increase in small thyroid cancer cases, the extent of resection during surgery has generally decreased. Therefore, questions have been raised about the efficacy and long-term side effects of TSH suppression therapy in patients who have undergone a lobectomy.
Methods
This is a multicenter, prospective, randomized, controlled clinical trial in which 2,986 patients with papillary thyroid cancer are randomized into a high-TSH group (intervention) and a low-TSH group (control) after having undergone a lobectomy. The principle of treatment includes a TSH-lowering regimen aimed at TSH levels between 0.3 and 1.99 μIU/mL in the low-TSH group. The high-TSH group targets TSH levels between 2.0 and 7.99 μIU/mL. The dose of levothyroxine will be adjusted at each visit to maintain the target TSH level. The primary outcome is recurrence-free survival, as assessed by neck ultrasound every 6 to 12 months. Secondary endpoints include disease-free survival, overall survival, success rate in reaching the TSH target range, the proportion of patients with major cardiovascular diseases or bone metabolic disease, the quality of life, and medical costs. The follow-up period is 5 years.
Conclusion
The results of this trial will contribute to establishing the optimal indication for TSH suppression therapy in low-risk papillary thyroid cancer patients by evaluating the benefit and harm of lowering TSH levels in terms of recurrence, metabolic complications, costs, and quality of life.

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Ja Kyung Lee, Eu Jeong Ku, Su-jin Kim, Woochul Kim, Jae Won Cho, Kyong Yeun Jung, Hyeong Won Yu, Yea Eun Kang, Mijin Kim, Hee Kyung Kim, Junsun Ryu, June Young Choi
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Clinical impact of coexistent chronic lymphocytic thyroiditis on central lymph node metastasis in low- to intermediate-risk papillary thyroid carcinoma: The MASTER study
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璐狄
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ASO Author Reflections: Active Surveillance may be Possible in Patients with T1b Papillary Thyroid Carcinoma Over 55 Years of Age Without High-Risk Features on Preoperative Examinations
Ho-Ryun Won, Eonju Jeon, Da Beom Heo, Jae Won Chang, Minho Shong, Je Ryong Kim, Hyemi Ko, Yea Eun Kang, Hyon-Seung Yi, Ju Hee Lee, Kyong Hye Joung, Ji Min Kim, Younju Lee, Sung-Woo Kim, Young Ju Jeong, Yong Bae Ji, Kyung Tae, Bon Seok Koo
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Age-Dependent Clinicopathological Characteristics of Patients with T1b Papillary Thyroid Carcinoma: Implications for the Possibility of Active Surveillance
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Mijin Kim, Yae Eun Kang, Young Joo Park, Bon Seok Koo, Eu Jeong Ku, June Young Choi, Eun Kyung Lee, Bo Hyun Kim
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Differentiated thyroid cancer: a focus on post-operative thyroid hormone replacement and thyrotropin suppression therapy
Benjamin J. Gigliotti, Sina Jasim
Endocrine.2023; 83(2): 251. CrossRef
Thyroid stimulating hormone suppression and recurrence after thyroid lobectomy for papillary thyroid carcinoma
Mi Rye Bae, Sung Hoon Nam, Jong-Lyel Roh, Seung-Ho Choi, Soon Yuhl Nam, Sang Yoon Kim
Endocrine.2022; 75(2): 487. CrossRef
The Concept of Economic Evaluation and Its Application in Thyroid Cancer Research
Kyungsik Kim, Mijin Kim, Woojin Lim, Bo Hyun Kim, Sue K. Park
Endocrinology and Metabolism.2021; 36(4): 725. 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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A Clinical Study on Hypopitutiarism: Significance of Combined Pituitary Stimulation Test.: Bo Youn Cho, Hong Gyu Lee, Chang Soon Koh, Hyung Kyu Park, Sook Kyung Kim, Chan Soo Shin, Seong Yeon Kim, Jae Seok Chun, Kyung Soo Park, Hyeon Kyu Kim, Sun Wook Kim; J Korean Endocr Soc. 1996;11(3):268-276. Published online November 7, 2019

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Abstract PDF: Background
Hypopituitarism can be caused by various diseases. Its clinical manifestations vary, depending on the extent and severity of the pituitary hormone deficiency. And some patients may initially present with SIADH-like features. Combined pituitary stimulation test has been used for the diagnosis of hypopituitarism and subsequent hormone replacement therapy. However, the test is laborious, expensive and uncomfortable to the patients, So we performed this study to know whether combined pituitary stimulation test can be replaced with clinical features and simple basal hormone concentrations. Methods: Fifty-four patients who were diagnosed as hypopituitarism by combined pituitary stimulation test were included in this study. Clinical features and basal hormone data were compared with the results of combined pituitary stimulation test for the evaluation of pituitary-gonadal, pituitary-thyroid, and pituitary-adrenal axes, using X2 test. Results: 1) In pituitary-gonadal axis, the evaluation of clinical features and basal gonad hormone concentrations were significantly consistent with stimulation test(p<0.05), 2) In pituitary-thyroid axis, the evaluation of basal thyroid hormone concentrations were more helpful than stimulation test though results of the two tests were not consistent. 3) In pituitary-adrenal axis, all patients whose basal cortisol concentrations were low showed inadequate responses to stimulation test. However, stimulation test revealed adrenal insufficiency in some patients with normal basal cortisol concentrations. 4) 9 patients who presented with SIADH-like features were older than the others and had all corticotropin deficiency. Conclusion: In patients with suspected hypopituitarism, the evaluation of clinical features and basal hormone concentrations can be sufficient for the diagnosis of hypopituitarism and hormone replacement therapy. However, stimulation test is necessary to investigate adrenal function in patients with normal basal cortisol concentrations. And hypopituitarism should be considered in old patients who present with SIADH-like features.

Thyroid
Prognosis of Differentiated Thyroid Carcinoma with Initial Distant Metastasis: A Multicenter Study in Korea: Hosu Kim, Hye In Kim, Sun Wook Kim, Jaehoon Jung, Min Ji Jeon, Won Gu Kim, Tae Yong Kim, Hee Kyung Kim, Ho-Cheol Kang, Ji Min Han, Yoon Young Cho, Tae Hyuk Kim, Jae Hoon Chung; Endocrinol Metab. 2018;33(2):287-295. Published online June 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.2.287

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Background

Most patients with differentiated thyroid cancer (DTC) have a favorable prognosis. However, patients with DTC and initial distant metastasis have not been commonly found, and their clinical characteristics have seldom been reported. In this study, we analyzed the clinical features and prognosis of patients with DTC and initial distant metastasis in Korea.

Methods

We retrospectively reviewed the clinical data of 242 patients with DTC and initial distant metastasis treated from 1994 to 2013, collected from five tertiary hospitals in Korea.

Results

The patients' median age was 51 years, and 65% were women. They were followed for a median of 7 years. Lung was the most common site of distant metastasis: only lung 149 patients (62%), only bone 49 (20%), other single site one (pleura), and combined sites 43 (40 were lung and bone, two were bone and other site, and one was lung and other site). At the time of diagnosis, 50 patients (21%) had non-radioactive iodine (RAI) avidity. Five-year disease-specific survival (DSS) was 85% and 10-year DSS was 68%, which were better than those in previous studies. After multivariate analysis, old age, male sex, metastatic site, and histologic type (follicular type) were significant factors for poor prognosis. However, negative RAI avidity status was not a significant prognostic factor after adjusting for other variables.

Conclusion

The prognosis of Korean patients with DTC and initial distant metastasis was better than in previous studies. Old age, male sex, metastasis site, and histologic type were significant prognostic factors.

Citations

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Luca Giovanella, Murat Tuncel, Atena Aghaee, Alfredo Campenni, Armando De Virgilio, Petra Petranović Ovčariček
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Molecular Theranostics in Radioiodine-Refractory Differentiated Thyroid Cancer
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Joonseon Park, Kwangsoon Kim, Dong-Jun Lim, Ja Seong Bae, Jeong Soo Kim
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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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Abstract PDF Supplementary Material PubReader

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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The association between vitamin D supplementation and the long-term prognosis of differentiated thyroid cancer patients: a retrospective observational cohort study with propensity score matching
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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
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Prognosis of Differentiated Thyroid Carcinoma with Initial Distant Metastasis: A Multicenter Study in Korea
Hosu Kim, Hye In Kim, Sun Wook Kim, Jaehoon Jung, Min Ji Jeon, Won Gu Kim, Tae Yong Kim, Hee Kyung Kim, Ho-Cheol Kang, Ji Min Han, Yoon Young Cho, Tae Hyuk Kim, Jae Hoon Chung
Endocrinology and Metabolism.2018; 33(2): 287. CrossRef
Decreasing Disease-Specific Mortality of Differentiated Thyroid Cancer in Korea: A Multicenter Cohort Study
Min Ji Jeon, Hee Kyung Kim, Eun Heui Kim, Eun Sook Kim, Hyon-Seung Yi, Tae Yong Kim, Ho-Cheol Kang, Young Kee Shong, Won Bae Kim, Bo Hyun Kim, Won Gu Kim
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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; Correction in: Endocrinol Metab 2023;38(3):357

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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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Clinical Study
Triiodothyronine Levels Are Independently Associated with Metabolic Syndrome in Euthyroid Middle-Aged Subjects: Hye Jeong Kim, Ji Cheol Bae, Hyeong Kyu Park, Dong Won Byun, Kyoil Suh, Myung Hi Yoo, Jae Hyeon Kim, Yong-Ki Min, Sun Wook Kim, Jae Hoon Chung; Endocrinol Metab. 2016;31(2):311-319. Published online May 13, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.2.311

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Abstract PDF Supplementary Material PubReader

Background

Recent studies have shown an association between thyroid hormone levels and metabolic syndrome (MetS) among euthyroid individuals; however, there have been some inconsistencies between studies. Here, we evaluated the relationship between thyroid hormone levels and MetS in euthyroid middle-aged subjects in a large cohort.

Methods

A retrospective analysis of 13,496 euthyroid middle-aged subjects who participated in comprehensive health examinations was performed. Subjects were grouped according to thyroid stimulating hormone, total triiodothyronine (T3), total thyroxine (T4), and T3-to-T4 ratio quartile categories. We estimated the odds ratios (ORs) for MetS according to thyroid hormone quartiles using logistic regression models, adjusted for potential confounders.

Results

Of the study patients, 12% (n=1,664) had MetS. A higher T3 level and T3-to-T4 ratio were associated with unfavourable metabolic profiles, such as higher body mass index, systolic and diastolic blood pressure, triglycerides, fasting glucose and glycated hemoglobin, and lower high density lipoprotein cholesterol levels. The proportion of participants with MetS increased across the T3 quartile categories (P for trend <0.001) and the T3-to-T4 ratio quartile categories (P for trend <0.001). The multi-variate-adjusted OR (95% confidence interval) for MetS in the highest T3 quartile group was 1.249 (1.020 to 1.529) compared to the lowest T3 quartile group, and that in the highest T3-to-T4 ratio quartile group was 1.458 (1.141 to 1.863) compared to the lowest T3-to-T4 ratio quartile group, even after adjustment for potential confounders.

Conclusion

Serum T3 levels and T3-to-T4 ratio are independently associated with MetS in euthyroid middle-aged subjects. Longitudinal studies are needed to define this association and its potential health implications.

Citations

Citations to this article as recorded by

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Clinical Study
Economic Evaluation of Recombinant Human Thyroid Stimulating Hormone Stimulation vs. Thyroid Hormone Withdrawal Prior to Radioiodine Ablation for Thyroid Cancer: The Korean Perspective: Seo Young Sohn, Hye Won Jang, Yoon Young Cho, Sun Wook Kim, Jae Hoon Chung; Endocrinol Metab. 2015;30(4):531-542. Published online December 31, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.4.531

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43 Download
9 Web of Science
8 Crossref

Abstract PDF PubReader

Background

Previous studies have suggested that recombinant human thyroid stimulating hormone (rhTSH) stimulation is an acceptable alternative to thyroid hormone withdrawal (THW) when radioiodine remnant ablation is planned for thyroid cancer treatment, based on superior short-term quality of life with non-inferior remnant ablation efficacy. This study evaluated the cost-effectiveness of radioiodine remnant ablation using rhTSH, compared with the traditional preparation method which renders patients hypothyroid by THW, in Korean perspective.

Methods

This economic evaluation considered the costs and benefits to the Korean public healthcare system. Clinical experts were surveyed regarding the current practice of radioiodine ablation in Korea and their responses helped inform assumptions used in a cost effectiveness model. Markov modelling with 17 weekly cycles was used to assess the incremental costs per quality-adjusted life year (QALY) associated with rhTSH. Clinical inputs were based on a multi-center, randomized controlled trial comparing remnant ablation success after rhTSH preparation with THW. The additional costs associated with rhTSH were considered relative to the clinical benefits and cost offsets.

Results

The additional benefits of rhTSH (0.036 QALY) are achieved with an additional cost of Korean won ₩961,105, equating to cost per QALY of ₩26,697,361. Sensitivity analyses had only a modest impact upon cost-effectiveness, with one-way sensitivity results of approximately ₩33,000,000/QALY.

Conclusion

The use of rhTSH is a cost-effective alternative to endogenous hypothyroid stimulation prior to radioiodine ablation for patients who have undergone thyroidectomy in Korea.

Citations

Citations to this article as recorded by

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Clinical Study
Characteristics of Korean Patients with Antithyroid Drug-Induced Agranulocytosis: A Multicenter Study in Korea: Hee Kyung Kim, Jee Hee Yoon, Min Ji Jeon, Tae Yong Kim, Young Kee Shong, Min Jin Lee, Bo Hyun Kim, In Joo Kim, Ji Young Joung, Sun Wook Kim, Jae Hoon Chung, Ho-Cheol Kang; Endocrinol Metab. 2015;30(4):475-480. Published online December 31, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.4.475

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Abstract PDF PubReader

Background

Antithyroid drugs (ATDs) can lead to the development of agranulocytosis, which is the most serious adverse effect. Characteristics of ATD-induced agranulocytosis (AIA) have seldom been reported due to the rarity. In this study, we characterized the clinical features for AIA in Korean patients.

Methods

We retrospectively reviewed data from patients with AIA diagnosed between 1997 and 2014 at four tertiary hospitals. Agranulocytosis was defined as an absolute neutrophil count (ANC) below 500/mm³.

Results

The mean age of the patients (11 males, 43 females) was 38.2±14.9 years. Forty-eight patients (88.9%) with AIA had fever and sore throat on initial presentation, 20.4% of patients developed AIA during the second course of treatment, and 75.9% of patients suffered AIA within 3 months after initiation of ATD. The patients taking methimazole (n=39) showed lower levels of ANC and more frequent use of granulocyte-macrophage colony-stimulating factor than propylthiouracil (n=15) users. The median duration of agranulocytosis was 5.5 days (range, 1 to 20). No differences were observed between the long (≥6 days) and short recovery time (≤5 days) groups in terms of age, gender, ATDs, duration of ATDs, or initial ANC levels. Four patients (7.4%) who were taking ATDs for less than 2 months died of sepsis on the first or second day of hospitalization.

Conclusion

The majority of AIA incidents occur in the early treatment period. Considering the high fatality rate of AIA, an early aggressive therapeutic approach is critical and patients should be well informed regarding the warning symptoms of the disease.

Citations

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