Endocrinology and Metabolism

Original Articles

Thyroid
Clinical Utility of Liquid Chromatography-Tandem Mass Spectrometry for Thyroglobulin Measurement in Comparison with Immunoradiometric Assay and Chemiluminescence Microparticle Immunoassay: Hyunju Park, Eungjun Yoon, Sang-Mi Kim, Tae Hyuk Kim, Jae Hoon Chung, Soo-Youn Lee, Sun Wook Kim; Endocrinol Metab. 2025;40(6):928-939. Published online August 26, 2025; DOI: https://doi.org/10.3803/EnM.2025.2413

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Background
The liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to overcome interference from thyroglobulin autoantibodies (TgAb); however, it has not yet been implemented in Korea. This study aimed to confirm the accuracy of LC-MS/MS compared to conventional methods and to identify its advantages in patients with thyroid carcinoma (TC).
Methods
A total of 206 TC and 18 Hashimoto’s thyroiditis samples were collected. TgAb-positive (TgAb-P) was defined as TgAb >60 U/mL. Tg testing was performed using LC-MS/MS, immunoradiometric assay (Tg-IRMA), and chemiluminescence microparticle immunoassay (Tg-CMIA). The interference of TgAb in LC-MS/MS and CMIA methods was evaluated through an in vitro TgAb spiking experiment.
Results
The frequency of TgAb-P in TC samples was 76.2%. Correlations between assays were as follows: Tg measurements made by LC-MS/MS (Tg-MS) and Tg-IRMA (R=0.93), Tg-MS and Tg-CMIA (R=0.96), and Tg-CMIA and Tg-IRMA (R=0.99), and it was lower in TgAb-P than TgAb-negative group. Clinical factors (total thyroidectomy, thyroid lobectomy, and Hashimoto’s thyroiditis) did not affect these correlations. In TgAb spiking experiments, Tg-CMIA showed false negatives in TgAb-P, whereas Tg-MS did not. Among 21 TC cases with highly suspicious disease recurrence but Tg-IRMA <1 ng/mL, Tg-MS detected Tg ≥0.5 ng/mL in six samples. However, there was no consistent pattern of recurrence or TgAb trends.
Conclusion
Correlations between assays were lower in TgAb-P cases. The spike test results show Tg-MS is less prone to false negatives in TgAb-P cases. Tg-MS may improve Tg detection in TgAb-P cases. However, we could not identify a distinct patient group with shared clinical features that would benefit from Tg-MS.

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LC‑MS/MS for Thyroglobulin: A Complementary Approach to Immunoassay Limitations for Thyroid Cancer
Se Hee Park, Dong Yeob Shin
Endocrinology and Metabolism.2025; 40(6): 866. CrossRef

Thyroid
Adequate Dose of Levothyroxine for Thyroid-Stimulating Hormone Suppression after Total Thyroidectomy in Patients with Differentiated Thyroid Cancer: Hyun Jin Ryu, Min Sun Choi, Hyunju Park, Tae Hyuk Kim, Jae Hoon Chung, So Young Park, Sun Wook Kim; Endocrinol Metab. 2024;39(4):615-621. Published online August 7, 2024; DOI: https://doi.org/10.3803/EnM.2023.1896

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Background
The adequate dose of levothyroxine (LT4) for patients who have undergone total thyroidectomy (TT) for differentiated thyroid cancer (DTC) is uncertain. We evaluated the LT4 dose required to achieve mild thyroid-stimulating hormone (TSH) suppression in DTC patients after TT.
Methods
The electronic medical records of patients who underwent TT for DTC and received mild TSH suppression therapy were reviewed. Linear regression analysis was performed to evaluate the association between LT4 dose (μg/kg) and an ordinal group divided by body mass index (BMI). We also evaluated the trend in LT4 doses among groups divided by BMI and age.
Results
In total, 123 patients achieved mild TSH suppression (0.1 to 0.5 mIU/L). The BMI variable was divided into three categories: <23 kg/m² (n=46), ≥23 and <25 kg/m² (n=30), and ≥25 kg/m² (n=47). In the linear regression analysis, BMI was negatively associated with the LT4 dose after adjusting for age and sex (P<0.001). The LT4 doses required to achieve mild TSH suppression based on the BMI categories were 1.86, 1.71, and 1.71 μg/kg, respectively (P for trend <0.001). Further analysis with groups divided by age and BMI revealed that a higher BMI was related to a lower LT4 dose, especially in younger patients aged 20 to 39 (P for trend=0.011).
Conclusion
The study results suggest an appropriate LT4 dose for mild TSH suppression after TT based on body weight in patients with DTC. Considering body weight, BMI, and age in estimating LT4 doses might help to achieve the target TSH level promptly.

Citations

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A paper-based fluorescent aptasensor utilizing click chemistry strategy for portable detection of thyroid stimulating hormone
Changxin Huangfu, Yanting Duan, Chenyue Zhan, Ruimin Liang, Jiajie Xu, Minghua Ge
Microchemical Journal.2026; 225: 118035. CrossRef
Effects of 131I and TSH suppression therapy on METTL3, METTL14 levels and recurrence in thyroid cancer
Li-Guo Yang
American Journal of Cancer Research.2025; 15(1): 42. CrossRef
Developing a machine learning-based predictive model for levothyroxine dosage estimation in hypothyroid patients: a retrospective study
Tran Thi Ngan, Dang Huong Tra, Ngo Thi Quynh Mai, Hoang Van Dung, Nguyen Van Khai, Pham Van Linh, Nguyen Thi Thu Phuong
Frontiers in Endocrinology.2025;[Epub] CrossRef
Tailoring TSH suppression in differentiated thyroid carcinoma: evidence, controversies, and future directions
Xinxin Song, Xin Zhi, Linxue Qian
Endocrine.2025; 89(1): 1. CrossRef
Risk of Osteoporotic Fractures among Patients with Thyroid Cancer: A Nationwide Population-Based Cohort Study
Eu Jeong Ku, Won Sang Yoo, Yu Been Hwang, Subin Jang, Jooyoung Lee, Shinje Moon, Eun Kyung Lee, Hwa Young Ahn
Endocrinology and Metabolism.2025; 40(2): 225. CrossRef
Levothyroxine Dosing for Thyroid-Stimulating Hormone Suppression in Patients with Differentiated Thyroid Cancer after Total Thyroidectomy
Mijin Kim
Endocrinology and Metabolism.2024; 39(4): 576. CrossRef

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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Identification of recurrent pathogenic SERPINA7 mutation causing coexistence of TBG-CD and hypothyroidism in Indian pedigrees: in Silico structural analysis of mutant TBG and literature reappraisal
Smita Gawandi, Harshlata Khati, Gaurav Malhotra, Nawab Singh Baghel
Thyroid Research.2026;[Epub] CrossRef
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

Response

Thyroid
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; Endocrinol Metab. 2022;37(6):949-950. Published online November 10, 2022; DOI: https://doi.org/10.3803/EnM.2022.601

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Original Articles

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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International Journal of Molecular Sciences.2026; 27(3): 1497. CrossRef
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Adrian Harvey, Eric Walser, Rebecca Lahamm-Andraos, Caitlin Yeo, Samantha Wolfe, Cynthia Stretch, Steven Craig, Oliver F. Bathe
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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
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Mineral, Bone & Muscle
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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Arlingga Pratama, Gadis Meinar Sari, Dwikora Novembri Utomo
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