Endocrinology and Metabolism

Original Articles

Comparison of Ultrasensitive and Highly Sensitive Assay to Predict Stimulated Thyroglobulin Levels Using Unstimulated Levels in Differentiated Thyroid Cancer Patients: Jinsun Jang, Hyun Joo Kim, Seunggyun Ha, Kyong Yeun Jung, Gyeongseo Jung, Sun Wook Cho, Do Joon Park, Gi Jeong Cheon, Young Joo Park; Received January 6, 2025 Accepted March 20, 2025 Published online June 5, 2025; DOI: https://doi.org/10.3803/EnM.2025.2302 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Thyroglobulin (Tg) measurement is an essential aspect of monitoring for differentiated thyroid cancer (DTC) patients. This study compared the performances of ultrasensitive Tg (ultraTg) and highly sensitive Tg (hsTg) assays in predicting stimulated Tg levels without thyroid-stimulating hormone stimulation.
Methods
Overall, 268 DTC patients who had undergone total thyroidectomy and either radioiodine treatment or I-123 diagnostic scanning were included. Unstimulated and stimulated Tg levels were measured using hsTg (BRAHMS Dynotest Tg-plus) and ultraTg (RIAKEY Tg immunoradiometric assay) assays. Correlations of each assay with the ability of unstimulated Tg levels to predict stimulated Tg ≥1 ng/mL were analyzed.
Results
hsTg and ultraTg showed a strong correlation (R=0.79, P<0.01); the correlation was weaker in Tg antibody-positive patients (R=0.52). UltraTg demonstrated higher sensitivity in predicting stimulated Tg ≥1 ng/mL compared with hsTg. The optimal cut-off for ultraTg was 0.12 ng/mL (sensitivity, 72.0%; specificity, 67.2%). hsTg at 0.105 ng/mL had lower sensitivity (39.8%) but higher specificity (91.5%). Eight discordant cases with low hsTg (<0.2 ng/mL) but elevated ultraTg (>0.23 ng/mL) were identified; three developed structural recurrence within 3.4 to 5.8 years. Two patients had an excellent response according to hsTg but an indeterminate or biochemical incomplete response according to ultraTg.
Conclusion
UltraTg demonstrated higher sensitivity in predicting positive stimulated Tg levels and potential recurrence compared with hsTg. However, its lower specificity may lead to more frequent classifications of biochemical incomplete response. UltraTg may be beneficial in clinically suspicious cases where hsTg falls below the cut-off, but its broader applicability requires further investigation.

Thyroid
Study Protocol of Expanded Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro-EXP): Jae Hoon Moon, Eun Kyung Lee, Wonjae Cha, Young Jun Chai, Sun Wook Cho, June Young Choi, Sung Yong Choi, A Jung Chu, Eun-Jae Chung, Yul Hwangbo, Woo-Jin Jeong, Yuh-Seog Jung, Kyungsik Kim, Min Joo Kim, Su-jin Kim, Woochul Kim, Yoo Hyung Kim, Chang Yoon Lee, Ji Ye Lee, Kyu Eun Lee, Young Ki Lee, Hunjong Lim, Do Joon Park, Sue K. Park, Chang Hwan Ryu, Junsun Ryu, Jungirl Seok, Young Shin Song, Ka Hee Yi, Hyeong Won Yu, Eleanor White, Katerina Mastrocostas, Roderick J. Clifton-Bligh, Anthony Glover, Matti L. Gild, Ji-hoon Kim, Young Joo Park; Endocrinol Metab. 2025;40(2):236-246. Published online February 18, 2025; DOI: https://doi.org/10.3803/EnM.2024.2136

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Abstract PDF Supplementary Material PubReader ePub: Background
Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making.
Methods
This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes.
Conclusion
This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.

Thyroid
Distinct Impacts of Clinicopathological and Mutational Profiles on Long-Term Survival and Recurrence in Medullary Thyroid Carcinoma: Moon Young Oh, Kyong Yeun Jung, Hoonsung Choi, Young Jun Chai, Sun Wook Cho, Su-jin Kim, Kyu Eun Lee, Eun-Jae Chung, Do Joon Park, Young Joo Park, Han-Kwang Yang; Endocrinol Metab. 2024;39(6):877-890. Published online November 5, 2024; DOI: https://doi.org/10.3803/EnM.2024.2027

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Abstract PDF Supplementary Material PubReader ePub: Background
Medullary thyroid carcinoma (MTC) has a poorer prognosis than differentiated thyroid cancers; however, comprehensive data on the long-term outcomes of MTC remain scarce. This study investigated the extended clinical outcomes of MTC and aimed to identify prognostic factors.
Methods
Patients diagnosed with MTC between 1980 and 2020 were retrospectively reviewed. Their clinical characteristics, longterm clinical outcomes, and prognostic factors for recurrence and mortality were analyzed.
Results
The study included 226 patients (144 women, 82 men). The disease-specific survival (DSS) rates for all MTC patients at 5-, 10-, 20-, and 30-year intervals were 92.7%, 89.4%, 74.3%, and 68.1%, respectively. The recurrence-free survival (RFS) rates were 71.1%, 56.1%, 40.2%, and 32.1% at these intervals. DSS was comparable between the groups from 1980–2009 and 2010–2020 (P=0.995); however, the 1980–2009 group had significantly lower RFS rates (P=0.031). The 2010–2020 group exhibited greater extents of surgical and lymph node dissection (P=0.003) and smaller tumors (P=0.003). Multivariate analysis identified extrathyroidal extension as the strongest prognostic factor for both RFS and DSS. Age >55 years and tumor size of ≥2 cm were also significant prognostic factors for DSS, while hereditary disease and lymph node metastasis were significant for RFS. Survival analysis after propensity-score matching of rearranged during transfection (RET)-negative and non-screened RET-positive groups showed comparable DSS but longer RFS in the RET-negative group.
Conclusion
Extrathyroidal extension was identified as the strongest prognostic factor for RFS and DSS. Older age and larger tumor size were associated with decreased DSS, while RET mutation and lymph node metastasis significantly impacted RFS.

Thyroid
Small Multi-Gene DNA Panel Can Aid in Reducing the Surgical Resection Rate and Predicting the Malignancy Risk of Thyroid Nodules: Moon Young Oh, Hye-Mi Choi, Jinsun Jang, Heejun Son, Seung Shin Park, Minchul Song, Yoo Hyung Kim, Sun Wook Cho, Young Jun Chai, Woosung Chung, Young Joo Park; Endocrinol Metab. 2024;39(5):777-792. Published online October 14, 2024; DOI: https://doi.org/10.3803/EnM.2024.2034

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Background
We explored the utility of a small multi-gene DNA panel for assessing molecular profiles of thyroid nodules and influencing clinical decisions by comparing outcomes between tested and untested nodules.
Methods
Between April 2022 and May 2023, we prospectively performed fine-needle aspiration (FNA) with gene testing via DNA panel of 11 genes (BRAF, RAS [NRAS, HRAS, KRAS], EZH1, DICER1, EIF1AX, PTEN, TP53, PIK3CA, TERT promoter) in 278 consecutive nodules (panel group). Propensity score-matching (1:1) was performed with 475 nodules that consecutively underwent FNA without gene testing between January 2021 and December 2021 (control group).
Results
In the panel group, positive call rate for mutations was 41.7% (BRAF 16.2%, RAS 12.6%, others 11.5%, double mutation 1.4%) for all nodules, and 40.0% (BRAF 4.3%, RAS 19.1%, others 15.7%, double mutation 0.9%) for indeterminate nodules. Benign call rate was 69.8% for all nodules, and 75.7% for indeterminate nodules. In four nodules, additional TP53 (in addition to BRAF or EZH1) or PIK3CA (in addition to BRAF or TERT) mutations were co-detected. Sensitivity, specificity, positive predictive value, and negative predictive value were 80.0%, 53.3%, 88.1%, 38.1% for all nodules, and 78.6%, 45.5%, 64.7%, 62.5% for indeterminate nodules, respectively. Panel group exhibited lower surgical resection rates than the control group for all nodules (27.0% vs. 52.5%, P<0.001), and indeterminate nodules (23.5% vs. 68.2%, P<0.001). Malignancy risk was significantly different between the panel and control groups (81.5% vs. 63.9%, P=0.008) for all nodules.
Conclusion
Our panel aids in managing thyroid nodules by providing information on malignancy risk based on mutations, potentially reducing unnecessary surgery in benign nodules or patients with less aggressive malignancies.

Citations

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Great Debate: Molecular Testing and Extent of Surgery in Well-Differentiated Thyroid Cancer
Cord Sturgeon, Ashok R. Shaha, Linwah Yip
Annals of Surgical Oncology.2025;[Epub] CrossRef

Thyroid
Diagnostic Accuracy of Preoperative Radiologic Findings in Papillary Thyroid Microcarcinoma: Discrepancies with the Postoperative Pathologic Diagnosis and Implications for Clinical Outcomes: Ying Li, Seul Ki Kwon, Hoonsung Choi, Yoo Hyung Kim, Sunyoung Kang, Kyeong Cheon Jung, Jae-Kyung Won, Do Joon Park, Young Joo Park, Sun Wook Cho; Endocrinol Metab. 2024;39(3):450-460. Published online May 27, 2024; DOI: https://doi.org/10.3803/EnM.2023.1872

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Abstract PDF Supplementary Material PubReader ePub: Background
The diagnostic accuracy of preoperative radiologic findings in predicting the tumor characteristics and clinical outcomes of papillary thyroid microcarcinoma (PTMC) was evaluated across all risk groups.
Methods
In total, 939 PTMC patients, comprising both low-risk and non-low-risk groups, who underwent surgery were enrolled. The preoperative tumor size and lymph node metastasis (LNM) were evaluated by ultrasonography within 6 months before surgery and compared with the postoperative pathologic findings. Discrepancies between the preoperative and postoperative tumor sizes were analyzed, and clinical outcomes were assessed.
Results
The agreement rate between radiological and pathological tumor size was approximately 60%. Significant discrepancies were noted, including an increase in tumor size in 24.3% of cases. Notably, in 10.8% of patients, the postoperative tumor size exceeded 1 cm, despite being initially classified as 0.5 to 1.0 cm based on preoperative imaging. A postoperative tumor size >1 cm was associated with aggressive pathologic factors such as multiplicity, microscopic extrathyroidal extension, and LNM, as well as a higher risk of distant metastasis. In 30.1% of patients, LNM was diagnosed after surgery despite not being suspected before the procedure. This group was characterized by smaller metastatic foci and lower risks of distant metastasis or recurrence than patients with LNM detected both before and after surgery.
Conclusion
Among all risk groups of PTMCs, a subset showed an increase in tumor size, reaching 1 cm after surgery. These cases require special consideration due to their association with adverse clinical outcomes, including an elevated risk of distant metastasis.

Review Articles

Thyroid
Active Surveillance for Low-Risk Thyroid Cancers: A Review of Current Practice Guidelines: Min Joo Kim, Jae Hoon Moon, Eun Kyung Lee, Young Shin Song, Kyong Yeun Jung, Ji Ye Lee, Ji-hoon Kim, Kyungsik Kim, Sue K. Park, Young Joo Park; Endocrinol Metab. 2024;39(1):47-60. Published online February 15, 2024; DOI: https://doi.org/10.3803/EnM.2024.1937

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The indolent nature and favorable outcomes associated with papillary thyroid microcarcinoma have prompted numerous prospective studies on active surveillance (AS) and its adoption as an alternative to immediate surgery in managing low-risk thyroid cancer. This article reviews the current status of AS, as outlined in various international practice guidelines. AS is typically recommended for tumors that measure 1 cm or less in diameter and do not exhibit aggressive subtypes on cytology, extrathyroidal extension, lymph node metastasis, or distant metastasis. To determine the most appropriate candidates for AS, factors such as tumor size, location, multiplicity, and ultrasound findings are considered, along with patient characteristics like medical condition, age, and family history. Moreover, shared decision-making, which includes patient-reported outcomes such as quality of life and cost-effectiveness, is essential. During AS, patients undergo regular ultrasound examinations to monitor for signs of disease progression, including tumor growth, extrathyroidal extension, or lymph node metastasis. In conclusion, while AS is a feasible and reliable approach for managing lowrisk thyroid cancer, it requires careful patient selection, effective communication for shared decision-making, standardized follow-up protocols, and a clear definition of disease progression.

Citations

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Proteomic Analysis of Tissue Proteins Related to Lateral Lymph Node Metastasis in Papillary Thyroid Microcarcinoma
Qiyao Zhang, Zhen Cao, Yuanyang Wang, Hao Wu, Zejian Zhang, Ziwen Liu
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Association Between Metabolic Dysfunction-Associated Steatotic Liver Disease and Thyroid Cancer
Sang Yi Moon, Minkook Son, Jung-Hwan Cho, Hye In Kim, Ji Min Han, Ji Cheol Bae, Sunghwan Suh
Thyroid®.2025; 35(1): 79. CrossRef
Navigating Active Surveillance for Low-Risk PTMC by Standardizing Ultrasound Evaluation: Key Takeaways from the Latest Korean Society of Thyroid Radiology Consensus Statements
Young Joo Park
Clinical Thyroidology®.2025; 37(1): 27. CrossRef
Assessing the Rise in Papillary Thyroid Cancer Incidence: A 38-Year Australian Study Investigating WHO Classification Influence
Steven Weller, Cordia Chu, Alfred King-yin Lam
Journal of Epidemiology and Global Health.2025;[Epub] CrossRef
A Personalized, Risk-Based Approach to Active Surveillance for Prostate Cancer with Takeaways from Broader Oncology Practices: A Mixed Methods Review
Jeroen J. Lodder, Sebastiaan Remmers, Roderick C. N. van den Bergh, Arnoud W. Postema, Pim J. van Leeuwen, Monique J. Roobol
Journal of Personalized Medicine.2025; 15(3): 84. CrossRef
Exploration of immunocytochemical biomarkers related to central lymph node metastasis in papillary thyroid microcarcinoma
Lulu Rong, Jie Wang, Qian Wang, Yanli Zhu, Wenhao Ren
Cytojournal.2025; 22: 18. CrossRef
Study Protocol of Expanded Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro-EXP)
Jae Hoon Moon, Eun Kyung Lee, Wonjae Cha, Young Jun Chai, Sun Wook Cho, June Young Choi, Sung Yong Choi, A Jung Chu, Eun-Jae Chung, Yul Hwangbo, Woo-Jin Jeong, Yuh-Seog Jung, Kyungsik Kim, Min Joo Kim, Su-jin Kim, Woochul Kim, Yoo Hyung Kim, Chang Yoon Le
Endocrinology and Metabolism.2025; 40(2): 236. CrossRef
2024 International Expert Consensus on US-guided Thermal Ablation for T1N0M0 Papillary Thyroid Cancer
Zhen-long Zhao, Shu-rong Wang, Jennifer Kuo, Bülent Çekiç, Lei Liang, Hossam Arafa Ghazi, Shu-hang Xu, Gerardo Amabile, Song-song Wu, Ajit Yadav, Gang Dong, Ingo Janssen, Bo-qiang Fan, Nobuhiro Fukunari, Jun-feng He, Le Thanh Dung, Song-yuan Yu, Sum Leong
Radiology.2025;[Epub] CrossRef
Ultrasound and gene-guided microwave ablation vs. surgery for low-risk papillary thyroid carcinoma: a prospective observational cohort study
Yunfang Yu, Yuxin Shen, Yujie Tan, Yisikandaer Yalikun, Tian Tian, Qingqing Tang, Qiyun Ou, Yue Zhu, Miaoyun Long
Precision Clinical Medicine.2025;[Epub] CrossRef
2023 Update of the Korean Thyroid Association Guidelines for the Management of Thyroid Nodules
Eun Kyung Lee, Young Joo Park
Clinical Thyroidology®.2024; 36(4): 153. CrossRef
Association between exercise habits and incident type 2 diabetes mellitus in patients with thyroid cancer: nationwide population-based study
Jiyun Park, Jin-Hyung Jung, Hyunju Park, Young Shin Song, Soo-Kyung Kim, Yong-Wook Cho, Kyungdo Han, Kyung-Soo Kim
BMC Medicine.2024;[Epub] CrossRef
Prediction of Recurrent Laryngeal Nerve Invasion in Thyroid Cancer by Ultrasound
Jin Hyang Jung, Eunji Kim, Byung Ju Kang
Journal of Surgical Ultrasound.2024; 11(1): 18. CrossRef
Advances in clinical research on ultrasound-guided radiofrequency ablation for papillary thyroid microcarcinoma
Hua Xu, Jin-yan Yang, Xing Zhao, Zhe Ma
Frontiers in Oncology.2024;[Epub] CrossRef
Systemic therapy for differentiated thyroid cancer with distant metastasis
Eun Kyung Lee
Journal of the Korean Medical Association.2024; 67(7): 484. CrossRef
Active Surveillance of Papillary Thyroid Cancer—A Feasibility Experience from a Tertiary Care Centre
Narmada Nangadda, Hetashvi Gondaliya, Deepali Bhat, Anirudh J. Shetty, Kranti S. Khadilkar, Shivaprasad Kumbenahalli Siddegowda, Basavaraj G. Sooragonda, Vijay Pillai, Vidhya Bhushan Rangappa, Vivek Shetty, Yogesh Madhav Dokhe, Trupti C. Kolur, Naveen Ban
Indian Journal of Surgical Oncology.2024;[Epub] CrossRef

Thyroid
A Narrative Review of the 2023 Korean Thyroid Association Management Guideline for Patients with Thyroid Nodules: Eun Kyung Lee, Young Joo Park, Chan Kwon Jung, Dong Gyu Na; Endocrinol Metab. 2024;39(1):61-72. Published online February 14, 2024; DOI: https://doi.org/10.3803/EnM.2024.1938

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The 2023 Korean Thyroid Association (KTA) Management Guideline for Patients with Thyroid Nodules constitute an update of the 2016 KTA guideline for thyroid nodules and cancers that focuses specifically on nodules. The 2023 guideline aim to offer updated guidance based on new evidence that reflects the changes in clinical practice since the 2016 KTA guideline. To update the 2023 guideline, a comprehensive literature search was conducted from January 2022 to May 2022. The literature search included studies, reviews, and other evidence involving human subjects that were published in English in MEDLINE (PubMed), Embase, and other relevant databases. Additional significant clinical trials and research studies published up to April 2023 were also reviewed. The limitations of the current evidence are discussed, and suggestions for areas in need of further research are identified. The purpose of this review is to provide a summary of the 2023 KTA guideline for the management of thyroid nodules released in May 2023 and to give a balanced insight with comparison of recent guidelines from other societies.

Citations

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Recomendaciones de la Sociedad Española de Endocrinología y Nutrición (SEEN) sobre «qué no hacer» en la práctica clínica
Juan José Díez, Emma Anda, Irene Bretón, Cintia González-Blanco, María Miguélez, Ana Zugasti, Alberto Fernández
Endocrinología, Diabetes y Nutrición.2025; 72(3): 101531. CrossRef
Association Between Metabolic Dysfunction-Associated Steatotic Liver Disease and Thyroid Cancer
Sang Yi Moon, Minkook Son, Jung-Hwan Cho, Hye In Kim, Ji Min Han, Ji Cheol Bae, Sunghwan Suh
Thyroid®.2025; 35(1): 79. CrossRef
Comparison of core-needle biopsy and repeat fine-needle aspiration biopsy for thyroid nodules with initially inconclusive findings: a systematic review, diagnostic accuracy meta-analysis, and meta-regression
Hendra Zufry, Timotius Ivan Hariyanto
Journal of the American Society of Cytopathology.2025; 14(3): 159. CrossRef
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Endocrinología, Diabetes y Nutrición (English ed.).2025; 72(3): 101531. CrossRef
Enhancing recurrent laryngeal nerve localization during transoral endoscopic thyroid surgery using augmented reality: a proof-of-concept study
Moon Young Oh, Yeonjin Choi, Taesoo Jang, Eun Kyung Choe, Hyoun-Joong Kong, Young Jun Chai
Annals of Surgical Treatment and Research.2025; 108(3): 135. CrossRef
Surgical Extent of Low-to-Intermediate Thyroid Cancer: Molecular Testing and Clinical Decision-Making
Jae Won Chang
International Journal of Thyroidology.2025; 18(1): 19. CrossRef
2023 Update of the Korean Thyroid Association Guidelines for the Management of Thyroid Nodules
Eun Kyung Lee, Young Joo Park
Clinical Thyroidology®.2024; 36(4): 153. CrossRef
Systemic therapy for differentiated thyroid cancer with distant metastasis
Eun Kyung Lee
Journal of the Korean Medical Association.2024; 67(7): 484. CrossRef
Educational exchange in thyroid core needle biopsy diagnosis: enhancing pathological interpretation through guideline integration and peer learning
Agnes Stephanie Harahap, Chan Kwon Jung
Journal of Pathology and Translational Medicine.2024; 58(5): 205. CrossRef
Standardized Ultrasound Evaluation for Active Surveillance of Low-Risk Thyroid Microcarcinoma in Adults: 2024 Korean Society of Thyroid Radiology Consensus Statement
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Original Articles

Thyroid
Hashimoto Thyroiditis and Mortality in Patients with Differentiated Thyroid Cancer: The National Epidemiologic Survey of Thyroid Cancer in Korea and Meta-Analysis: Injung Yang, Jae Myung Yu, Hye Soo Chung, Yoon Jung Kim, Yong Kyun Roh, Min Kyu Choi, Sung-ho Park, Young Joo Park, Shinje Moon; Endocrinol Metab. 2024;39(1):140-151. Published online January 3, 2024; DOI: https://doi.org/10.3803/EnM.2023.1748

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Background
Many studies have shown that Hashimoto’s thyroiditis (HT) acts as a protective factor in differentiated thyroid cancer (DTC), but little is known about its effects on mortality. Therefore, this study was performed to reveal the prognosis of HT on mortality in patients with DTC.
Methods
This study included two types of research results: retrospective cohort study using the National Epidemiologic Survey of Thyroid cancer (NEST) in Korea and meta-analysis study with the NEST data and eight selected studies.
Results
Of the 4,398 patients with DTC in NEST, 341 patients (7.8%) died during the median follow-up period of 15 years (interquartile range, 12.3 to 15.6). Of these, 91 deaths (2.1%) were related to DTC. HT was associated with a smaller tumor size and less aggressive DTC. In Cox regression analysis after adjusting for age and sex, patients with HT showed a significantly lower risk of all-cause death (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.52 to 0.96) and DTC-related death (HR, 0.33; 95% CI, 0.14 to 0.77). The analysis with inverse probability of treatment weight data adjusted for age, sex, and year of thyroid cancer registration showed similar association. The meta-analysis showed that patients with HT showed a lower risk of all-cause mortality (risk ratio [RR], 0.24; 95% CI, 0.13 to 0.47) and thyroid cancer-related mortality (RR, 0.23; 95% CI, 0.13 to 0.40) in comparison with patients without HT.
Conclusion
This study showed that DTC co-presenting with HT is associated with a low risk of advanced DTC and presents a low risk for all-cause and DTC-related death.

Citations

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Germline polymorphisms of the NOD2 pathway may predict the effectiveness of radioiodine in differentiated thyroid cancer treatment
M. Borowczyk, M. Kaczmarek-Ryś, S. Hryhorowicz, M. Sypniewski, D. Filipowicz, P. Dobosz, M. Oszywa, M. Ruchała, K. Ziemnicka
Journal of Endocrinological Investigation.2024; 47(12): 2969. CrossRef

Thyroid Big Data Articles (National Health Insurance Service Database)
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; Endocrinol Metab. 2023;38(4):436-444. Published online July 12, 2023; DOI: https://doi.org/10.3803/EnM.2023.1684

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Background
This study aimed to investigate the changes of incidence and treatment of choice for hyperthyroidism from 2003 to 2018 and explore the treatment-related complications and concomitant comorbidities in South Korea using data from the National Health Insurance Service.
Methods
This is a retrospective observational study. Hyperthyroidism was defined as a case having two or more diagnostic codes of thyrotoxicosis, with antithyroid drug intake for more than 6 months.
Results
The average age-standardized incidence of hyperthyroidism from 2003 to 2018 was 42.23 and 105.13 per 100,000 men and women, respectively. In 2003 to 2004, hyperthyroidism was most often diagnosed in patients in their 50s, but in 2017 to 2018, people were most often diagnosed in their 60s. During the entire period, about 93.7% of hyperthyroidism patients were prescribed with antithyroid drugs, and meanwhile, the annual rates of ablation therapy decrease from 7.68% in 2008 to 4.56% in 2018. Antithyroid drug-related adverse events, mainly agranulocytosis and acute hepatitis, as well as complications of hyperthyroidism such as atrial fibrillation or flutter, osteoporosis, and fractures, occurred more often in younger patients.
Conclusion
In Korea, hyperthyroidism occurred about 2.5 times more in women than in men, and antithyroid drugs were most preferred as the first-line treatment. Compared to the general population, hyperthyroid patients may have a higher risk of atrial fibrillation or flutter, osteoporosis, and fractures at a younger age.

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Unveiling Risk Factors for Treatment Failure in Patients with Graves’ Disease: A Nationwide Cohort Study in Korea
Jung A Kim, Kyeong Jin Kim, Jimi Choi, Kyoung Jin Kim, Eyun Song, Ji Hee Yu, Nam Hoon Kim, Hye Jin Yoo, Ji A Seo, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Sin Gon Kim
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International Journal of Thyroidology.2025; 18(1): 65. CrossRef
Long-term Effect of Thyrotropin-binding Inhibitor Immunoglobulin on Atrial Fibrillation in Euthyroid Patients
Jung-Chi Hsu, Kang-Chih Fan, Ting-Chuan Wang, Shu-Lin Chuang, Ying-Ting Chao, Ting-Tse Lin, Kuan-Chih Huang, Lian-Yu Lin, Lung-Chun Lin
Endocrine Practice.2024; 30(6): 537. CrossRef
Treatment Patterns and Preferences for Graves’ Disease in Korea: Insights from a Nationwide Cohort Study
Kyeong Jin Kim, Jimi Choi, Soo Myoung Shin, Jung A Kim, Kyoung Jin Kim, Sin Gon Kim
Endocrinology and Metabolism.2024; 39(4): 659. CrossRef
Dynamic Risk Model for the Medical Treatment of Graves’ Hyperthyroidism according to Treatment Duration
Meihua Jin, Chae A Kim, Min Ji Jeon, Won Bae Kim, Tae Yong Kim, Won Gu Kim
Endocrinology and Metabolism.2024; 39(4): 579. CrossRef
Effect of COVID-19 Vaccination on Thyroid Disease in 7 Million Adult and 0.2 Million Adolescent Vaccine Recipients
Sungho Bea, Hwa Young Ahn, Jieun Woo, Ju-Young Shin, Sun Wook Cho
The Journal of Clinical Endocrinology & Metabolism.2024;[Epub] CrossRef
The Current Status of Hyperthyroidism in Korea
Hyemi Kwon
Endocrinology and Metabolism.2023; 38(4): 392. CrossRef
Is Thyroid Dysfunction Associated with Unruptured Intracranial Aneurysms? A Population-Based, Nested Case–Control Study from Korea
Hyeree Park, Sun Wook Cho, Sung Ho Lee, Kangmin Kim, Hyun-Seung Kang, Jeong Eun Kim, Aesun Shin, Won-Sang Cho
Thyroid®.2023; 33(12): 1483. CrossRef

Thyroid Thyroid Cancer Screening
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; Endocrinol Metab. 2023;38(1):81-92. Published online February 27, 2023; DOI: https://doi.org/10.3803/EnM.2023.1668

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Background
The true benefit of thyroid cancer screening is incompletely understood. This study investigated the impact of ultrasound screening on thyroid cancer outcomes through a comparison with symptomatic thyroid cancer using data from a nationwide cohort study in Korea.
Methods
Cox regression analysis was performed to assess the hazard ratios (HRs) for all-cause and thyroid cancer-specific mortality. Considering the possible bias arising from age, sex, year of thyroid cancer registration, and confounding factors for mortality (including smoking/drinking status, diabetes, and hypertension), all analyses were conducted with stabilized inverse probability of treatment weighting (IPTW) according to the route of detection.
Results
Of 5,796 patients with thyroid cancer, 4,145 were included and 1,651 were excluded due to insufficient data. In comparison with the screening group, the clinical suspicion group was associated with large tumors (17.2±14.6 mm vs. 10.4±7.9 mm), advanced T stage (3–4) (odds ratio [OR], 1.24; 95% confidence interval [CI], 1.09 to 1.41), extrathyroidal extension (OR, 1.16; 95% CI, 1.02 to 1.32), and advanced stage (III–IV) (OR, 1.16; 95% CI, 1.00 to 1.35). In IPTW-adjusted Cox regression analysis, the clinical suspicion group had significantly higher risks of all-cause mortality (HR, 1.43; 95% CI, 1.14 to 1.80) and thyroid cancer-specific mortality (HR, 3.07; 95% CI, 1.77 to 5.29). Mediation analysis showed that the presence of thyroid-specific symptoms was directly associated with a higher risk of cancer-specific mortality. Thyroid-specific symptoms also indirectly affected thyroid cancer-specific mortality, mediated by tumor size and advanced clinicopathologic status.
Conclusion
Our findings provide important evidence for the survival benefit of early detection of thyroid cancer compared to symptomatic thyroid cancer.

Citations

Citations to this article as recorded by

Cost-Utility Analysis of Early Detection with Ultrasonography of Differentiated Thyroid Cancer: A Retrospective Study on a Korean Population
Han-Sang Baek, Jeonghoon Ha, Kwangsoon Kim, Ja Seong Bae, Jeong Soo Kim, Sungju Kim, Dong-Jun Lim, Chul-Min Kim
Endocrinology and Metabolism.2024; 39(2): 310. CrossRef
Thyroid cancer-specific mortality during 2005–2018 in Korea, aftermath of the overdiagnosis issue: a nationwide population-based cohort study
Kyeong Jin Kim, Jimi Choi, Sue K. Park, Young Joo Park, Sin Gon Kim
International Journal of Surgery.2024; 110(9): 5489. CrossRef
Distinct Impacts of Clinicopathological and Mutational Profiles on Long-Term Survival and Recurrence in Medullary Thyroid Carcinoma
Moon Young Oh, Kyong Yeun Jung, Hoonsung Choi, Young Jun Chai, Sun Wook Cho, Su-jin Kim, Kyu Eun Lee, Eun-Jae Chung, Do Joon Park, Young Joo Park, Han-Kwang Yang
Endocrinology and Metabolism.2024; 39(6): 877. CrossRef
Clinical Characteristics, Diagnostic Approach and Outcome of Thyroid Incidental Findings vs. Clinically Overt Thyroid Nodules: An Observational Single-Centre Study
Tom Jansen, Nike Stikkelbroeck, Annenienke van de Ven, Ilse van Engen-van Grunsven, Marcel Janssen, Han Bonenkamp, Martin Gotthardt, Romana T. Netea-Maier
Cancers.2023; 15(8): 2350. CrossRef
Lower Thyroid Cancer Mortality in Patients Detected by Screening: A Meta-Analysis
Shinje Moon, Young Shin Song, Kyong Yeun Jung, Eun Kyung Lee, Young Joo Park
Endocrinology and Metabolism.2023; 38(1): 93. CrossRef
To Screen or Not to Screen?
Do Joon Park
Endocrinology and Metabolism.2023; 38(1): 69. CrossRef
The 2017 United States Preventive Services Task Force Recommendation for Thyroid Cancer Screening Is No Longer the Gold Standard
Ka Hee Yi
Endocrinology and Metabolism.2023; 38(1): 72. CrossRef
Thyroid Cancer Screening: How to Maximize Its Benefits and Minimize Its Harms
Jung Hwan Baek
Endocrinology and Metabolism.2023; 38(1): 75. CrossRef

Thyroid Thyroid Cancer Screening
Lower Thyroid Cancer Mortality in Patients Detected by Screening: A Meta-Analysis: Shinje Moon, Young Shin Song, Kyong Yeun Jung, Eun Kyung Lee, Young Joo Park; Endocrinol Metab. 2023;38(1):93-103. Published online February 27, 2023; DOI: https://doi.org/10.3803/EnM.2023.1667

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Background
Thyroid cancer screening has contributed to the skyrocketing prevalence of thyroid cancer. However, the true benefit of thyroid cancer screening is not fully understood. This study aimed to evaluate the impact of screening on the clinical outcomes of thyroid cancer by comparing incidental thyroid cancer (ITC) with non-incidental thyroid cancer (NITC) through a meta-analysis.
Methods
PubMed and Embase were searched from inception to September 2022. We estimated and compared the prevalence of high-risk features (aggressive histology of thyroid cancer, extrathyroidal extension, metastasis to regional lymph nodes or distant organs, and advanced tumor-node-metastasis [TNM] stage), thyroid cancer-specific death, and recurrence in the ITC and NITC groups. We also calculated pooled risks and 95% confidence intervals (CIs) of the outcomes derived from these two groups.
Results
From 1,078 studies screened, 14 were included. In comparison to NITC, the ITC group had a lower incidence of aggressive histology (odds ratio [OR], 0.46; 95% CI, 0.31 to 0.7), smaller tumors (mean difference, −7.9 mm; 95% CI, −10.2 to −5.6), lymph node metastasis (OR, 0.64; 95% CI, 0.48 to 0.86), and distant metastasis (OR, 0.42; 95% CI, 0.23 to 0.77). The risks of recurrence and thyroid cancer-specific mortality were also lower in the ITC group (OR, 0.42; 95% CI, 0.25 to 0.71 and OR, 0.46; 95% CI, 0.28 to 0.74) than in the NITC group.
Conclusion
Our findings provide important evidence of a survival benefit from the early detection of thyroid cancer compared to symptomatic thyroid cancer.

Citations

Citations to this article as recorded by

Radioactive Iodine in Differentiated Thyroid Cancer: Effect on Detection of Distant Metastases Comparing 4 Guidelines
Merel T Stegenga, W Edward Visser, Robin P Peeters, Folkert J van Kemenade, Marco Medici, Tessa M van Ginhoven, Frederik A Verburg, Evert F S van Velsen
Journal of the Endocrine Society.2025;[Epub] CrossRef
Cost-Utility Analysis of Early Detection with Ultrasonography of Differentiated Thyroid Cancer: A Retrospective Study on a Korean Population
Han-Sang Baek, Jeonghoon Ha, Kwangsoon Kim, Ja Seong Bae, Jeong Soo Kim, Sungju Kim, Dong-Jun Lim, Chul-Min Kim
Endocrinology and Metabolism.2024; 39(2): 310. CrossRef
Thyroid nodules: diagnosis and management
Giorgio Grani, Marialuisa Sponziello, Sebastiano Filetti, Cosimo Durante
Nature Reviews Endocrinology.2024; 20(12): 715. CrossRef
Thyroid cancer-specific mortality during 2005–2018 in Korea, aftermath of the overdiagnosis issue: a nationwide population-based cohort study
Kyeong Jin Kim, Jimi Choi, Sue K. Park, Young Joo Park, Sin Gon Kim
International Journal of Surgery.2024; 110(9): 5489. CrossRef
To Screen or Not to Screen?
Do Joon Park
Endocrinology and Metabolism.2023; 38(1): 69. CrossRef
The 2017 United States Preventive Services Task Force Recommendation for Thyroid Cancer Screening Is No Longer the Gold Standard
Ka Hee Yi
Endocrinology and Metabolism.2023; 38(1): 72. CrossRef
Thyroid Cancer Screening: How to Maximize Its Benefits and Minimize Its Harms
Jung Hwan Baek
Endocrinology and Metabolism.2023; 38(1): 75. CrossRef
Delayed Surgery for and Outcomes of Papillary Thyroid Cancer: Is the Pendulum Still Swinging?
Giorgio Grani
Clinical Thyroidology.2023; 35(5): 192. CrossRef

Thyroid
BRAF^V600E Mutation Enhances Estrogen-Induced Metastatic Potential of Thyroid Cancer by Regulating the Expression of Estrogen Receptors: Minjun Kim, Su-jin Kim, Seong Yun Ha, Zhen Xu, Youngjin Han, Hyeon-Gun Jee, Sun Wook Cho, Young Joo Park, Kyu Eun Lee; Endocrinol Metab. 2022;37(6):879-890. Published online December 26, 2022; DOI: https://doi.org/10.3803/EnM.2022.1563

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Background
Cross-talk between mitogen-activated protein kinase and estrogen has been reported; however, the role of BRAF^V600E in the estrogen responsiveness of thyroid cancer is unknown. We elucidated the effect of BRAF^V600E on the estrogen-induced increase in metastatic potential in thyroid cancer.
Methods
Using a pair of cell lines, human thyroid cell lines which harbor wild type BRAF gene (Nthy/WT) and Nthy/BRAF^V600E (Nthy/V600E), the expression of estrogen receptors (ERs) and estrogen-induced metastatic phenotypes were evaluated. Susceptibility to ERα- and ERβ-selective agents was evaluated to confirm differential ER expression. ESR expression was analyzed according to BRAF^V600E status and age (≤50 years vs. >50 years) using The Cancer Genome Atlas (TCGA) data.
Results
Estradiol increased the ERα/ERβ expression ratio in Nthy/V600E, whereas the decreased ERα/ERβ expression ratio was found in Nthy/WT. BRAF^V600E-mutated cell lines showed a higher E2-induced increase in metastatic potential, including migration, invasion, and anchorage-independent growth compared with Nthy/WT. An ERα antagonist significantly inhibited migration in Nthy/V600E cells, whereas an ERβ agonist was more effective in Nthy/WT. In the BRAF^V600E group, ESR1/ESR2 ratio was significantly higher in younger age group (≤50 years) compared with older age group (>50 years) by TCGA data analysis.
Conclusion
Our data show that BRAF^V600E mutation plays a crucial role in the estrogen responsiveness of thyroid cancer by regulating ER expression. Therefore, BRAF^V600E might be used as a biomarker when deciding future hormone therapies based on estrogen signaling in thyroid cancer patients.

Citations

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The importance of protein domain mutations in cancer therapy
Kiran Kumar Chitluri, Isaac Arnold Emerson
Heliyon.2024; 10(6): e27655. CrossRef
Three cases of thyroid cancer in transgender female veterans receiving gender-affirming estrogen treatment
John D. Christensen, Hiba T. Basheer
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Thyroid Cancer Prevalence, Risk Exposure, and Clinical Features Among Transgender Female Veterans
John David Christensen, Hiba T Basheer, Jose Joaquin Lado Abeal
Journal of the Endocrine Society.2024;[Epub] CrossRef
A review of complex hormone regulation in thyroid cancer: novel insights beyond the hypothalamus–pituitary–thyroid axis
Liu-han Chen, Tao Xie, Qian Lei, Yan-rui Gu, Chuan-zheng Sun
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Genes Co-Expressed with ESR2 Influence Clinical Outcomes in Cancer Patients: TCGA Data Analysis
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Preoperative Diagnosis of Cervical Lymph Node Metastasis in Papillary Thyroid Carcinoma
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Association of DNA Promoter Methylation and BRAF Mutation in Thyroid Cancer
Farzana Jasmine, Briseis Aschebrook-Kilfoy, Mohammad M. Rahman, Garrett Zaagman, Raymon H. Grogan, Mohammed Kamal, Habibul Ahsan, Muhammad G. Kibriya
Current Oncology.2023; 30(3): 2978. CrossRef
Editorial: Recent advances in papillary thyroid carcinoma: Progression, treatment and survival predictors
Erivelto Martinho Volpi, Margarita Carmen Ramirez-Ortega, Jose Federico Carrillo
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Letter

Thyroid
Re-Increasing Trends in Thyroid Cancer Incidence after a Short Period of Decrease in Korea: Reigniting the Debate on Ultrasound Screening: Chan Kwon Jung, Ja Seong Bae, Young Joo Park; Endocrinol Metab. 2022;37(5):816-818. Published online October 11, 2022; DOI: https://doi.org/10.3803/EnM.2022.1586

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Bilateral axillo-breast approach robotic total thyroidectomy without isthmectomy: a case report
Hyeji Kim, Hyeonuk Hwang, Hyungju Kwon
The Ewha Medical Journal.2024;[Epub] CrossRef
Contents analysis of thyroid cancer-related information uploaded to YouTube by physicians in Korea: endorsing thyroid cancer screening, potentially leading to overdiagnosis
EunKyo Kang, HyoRim Ju, Soojeong Kim, Juyoung Choi
BMC Public Health.2024;[Epub] CrossRef
Cost-Utility Analysis of Early Detection with Ultrasonography of Differentiated Thyroid Cancer: A Retrospective Study on a Korean Population
Han-Sang Baek, Jeonghoon Ha, Kwangsoon Kim, Ja Seong Bae, Jeong Soo Kim, Sungju Kim, Dong-Jun Lim, Chul-Min Kim
Endocrinology and Metabolism.2024; 39(2): 310. CrossRef
Thyroid Cancer Incidence Among Korean Individuals: A Comparison of South Korea and the United States
Dohun Kim, Guan Li, Peter K. Moon, Yifei Ma, Soohyun Sim, Sung Y. Park, Minkyung Oh, Uchechukwu C. Megwalu
The Laryngoscope.2024; 134(9): 4156. CrossRef
Thyroid cancer-specific mortality during 2005–2018 in Korea, aftermath of the overdiagnosis issue: a nationwide population-based cohort study
Kyeong Jin Kim, Jimi Choi, Sue K. Park, Young Joo Park, Sin Gon Kim
International Journal of Surgery.2024; 110(9): 5489. CrossRef
Changing Trends of Thyroid Cancer Clinical Characteristics and Treatment Pattern in South Korea: Insights from an Institutional Database and the Korean Cancer Center Registry Database
Yung Jee Kang, Nayeon Choi, Jungirl Seok, Sun Wook Kim, Tae-Hyuk Kim, Jae Hoon Chung, Young-Ik Son, Man Ki Chung
International Journal of Thyroidology.2024; 17(2): 277. 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

Original Article

Thyroid
Clinical Outcomes of Repeated Radioactive Iodine Therapy for Graves’ Disease: Min Joo Kim, Sun Wook Cho, Ye An Kim, Hoon Sung Choi, Young Joo Park, Do Joon Park, Bo Youn Cho; Endocrinol Metab. 2022;37(3):524-532. Published online June 16, 2022; DOI: https://doi.org/10.3803/EnM.2022.1418

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Background
Radioactive iodine (RAI) therapy is a successful therapeutic modality for Graves’ disease. However, RAI therapy can fail, and RAI therapy after antithyroid drugs (ATDs) has a lower remission rate. Therefore, many patients require repeated RAI therapy. This study investigated the clinical outcomes of repeated RAI therapy for Graves’ disease.
Methods
Patients who underwent RAI therapy as second-line therapy after failure of ATD treatment between 2001 and 2015 were reviewed. Remission was defined as hypothyroid or euthyroid status without ATD, and with or without levothyroxine at 12 months after RAI therapy.
Results
The 1-year remission rate after 2nd RAI therapy (66%, 152/230) is significantly higher than that after 1st RAI therapy (48%, 393/815) or long-term ATD treatment after 1st RAI therapy failure (42%). The clinical response to 2nd RAI therapy was more rapid. The median time intervals from the 2nd RAI therapy to ATD discontinuation (1.3 months) and to the start of levothyroxine replacement (2.5 months) were significantly shorter than those for the 1st RAI therapy. A smaller goiter size, a longer time interval between the 1st and 2nd RAI therapies, and a longer ATD discontinuation period predicted remission after the 2nd RAI therapy. Finally, in 78 patients who failed the 2nd RAI therapy, the mean ATD dosage significantly reduced 5.1 mg over 12 months.
Conclusion
Repeated RAI therapy can be a good therapeutic option, especially in patients with smaller goiters and those who are more responsive to the 1st RAI therapy.

Citations

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Outcomes of Fixed-Dose Radioactive Iodine Therapy in Hyperthyroidism and Optimization of Follow-Up After Treatment Failure With Low-Dose Antithyroid Medication
Panita Kantikool, Naphat Buraphanawibun
Cureus.2025;[Epub] CrossRef
Prospective study to evaluate radioactive iodine of 20 mCi vs 10–15 mCi in Graves’ disease
Wasit Kanokwongnuwat, Nawarat Penpong
BMC Endocrine Disorders.2024;[Epub] CrossRef
The Early Changes in Thyroid-Stimulating Immunoglobulin Bioassay over Anti-Thyroid Drug Treatment Could Predict Prognosis of Graves’ Disease
Jin Yu, Han-Sang Baek, Chaiho Jeong, Kwanhoon Jo, Jeongmin Lee, Jeonghoon Ha, Min Hee Kim, Jungmin Lee, Dong-Jun Lim
Endocrinology and Metabolism.2023; 38(3): 338. CrossRef
Effect of liver dysfunction on outcome of radioactive iodine therapy for Graves’ disease
Yuyang Ze, Fei Shao, Xuefeng Feng, Shanmei Shen, Yan Bi, Dalong Zhu, Xiaowen Zhang
BMC Endocrine Disorders.2022;[Epub] CrossRef

Letter

Thyroid
Transarterial Radioembolization as an Effective Local Treatment Modality for Liver Metastasis of Thyroid Cancer: Yoo Hyung Kim, Hyo-Cheol Kim, Yun Bin Lee, Samina Park, Eun-Jae Chung, Jin Chul Paeng, Young Joo Park; Endocrinol Metab. 2022;37(2):383-385. Published online April 13, 2022; DOI: https://doi.org/10.3803/EnM.2022.1437

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Citations

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Thyroid Gland as a Metastatic Site for Hepatocellular Carcinoma: A Rare Case Report
Yang-Lu Ge, Shui-Quan Jin, Lv-Zhou Han, Xiang Zhang
OncoTargets and Therapy.2024; Volume 17: 1033. CrossRef

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