Endocrinology and Metabolism

Review Article

Thyroid
2025 Korean Thyroid Association Clinical Management Guideline on Active Surveillance for Low-Risk Papillary Thyroid Carcinoma: Eun Kyung Lee, Min Joo Kim, Seung Heon Kang, Bon Seok Koo, Kyungsik Kim, Mijin Kim, Bo Hyun Kim, Ji-hoon Kim, Shinje Moon, Kyorim Back, Young Shin Song, Jong-hyuk Ahn, Hwa Young Ahn, Ho-Ryun Won, Won Sang Yoo, Min Kyoung Lee, Jeongmin Lee, Ji Ye Lee, Kyong Yeun Jung, Chan Kwon Jung, Yoon Young Cho, Dong-Jun Lim, Sun Wook Kim, Young Joo Park, Dong Gyu Na, Jee Soo Kim; Endocrinol Metab. 2025;40(3):307-341. Published online June 24, 2025; DOI: https://doi.org/10.3803/EnM.2025.2461

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Abstract PDF PubReader ePub: The increasing detection of papillary thyroid microcarcinoma (PTMC) has raised concerns regarding overtreatment. For low-risk PTMC, either immediate surgery or active surveillance (AS) can be considered. To facilitate the implementation of AS, the Korean Thyroid Association convened a multidisciplinary panel and developed the first Korean guideline. AS is recommended for adults with pathologically confirmed Bethesda V–VI PTMC who have no clinical evidence of lymph node or distant metastasis, gross extrathyroidal extension, invasion of the trachea or recurrent laryngeal nerve, or aggressive histology. A baseline assessment requires high-resolution neck ultrasound performed by experienced operators to exclude extrathyroidal extension, tracheal or recurrent laryngeal nerve invasion, and lymph node metastasis; contrast-enhanced neck computed tomography is optional. Patient characteristics, including age, comorbidities, and the capacity for long-term follow-up, should be thoroughly assessed. Shared decision-making should carefully weigh the benefits and risks of surgery versus AS, considering expected oncologic outcomes, potential complications, quality of life, anxiety, medical costs, and patient preference. Follow-up involves neck ultrasound and thyroid function tests every 6 months for 2 years and annually thereafter. Disease progression, defined as significant tumor growth or newly detected nodal or distant metastasis, warrants surgery. Despite remaining uncertainties, this guideline provides a structured framework to ensure oncologic safety and supports patient-centered AS.

Editorial

Thyroid
Long-Term Outcomes of Radiofrequency Ablation in Patients with Low-Risk Papillary Thyroid Microcarcinoma: Hunjong Lim, Min Joo Kim; Endocrinol Metab. 2025;40(3):385-387. Published online June 11, 2025; DOI: https://doi.org/10.3803/EnM.2025.2432

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Original Article

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.

Review Article

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
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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
Global research landscape on active surveillance for papillary thyroid microcarcinoma: a bibliometric analysis
Dong-Shu Kang, Yu-Hao Lin, Jian-Qing Tian
Discover Oncology.2025;[Epub] CrossRef
2025 Korean Thyroid Association Clinical Management Guideline on Active Surveillance for Low-Risk Papillary Thyroid Carcinoma
Eun Kyung Lee, Min Joo Kim, Seung Heon Kang, Bon Seok Koo, Kyungsik Kim, Mijin Kim, Bo Hyun Kim, Ji-hoon Kim, Shin Je Moon, Kyorim Back, Young Shin Song, Jong-hyuk Ahn, Hwa Young Ahn, Ho-Ryun Won, Won Sang Yoo, Min Kyoung Lee, Jeongmin Lee, Ji Ye Lee, Kyo
International Journal of Thyroidology.2025; 18(1): 30. CrossRef
2025 Korean Thyroid Association Clinical Management Guideline on Active Surveillance for Low-Risk Papillary Thyroid Carcinoma
Eun Kyung Lee, Min Joo Kim, Seung Heon Kang, Bon Seok Koo, Kyungsik Kim, Mijin Kim, Bo Hyun Kim, Ji-hoon Kim, Shinje Moon, Kyorim Back, Young Shin Song, Jong-hyuk Ahn, Hwa Young Ahn, Ho-Ryun Won, Won Sang Yoo, Min Kyoung Lee, Jeongmin Lee, Ji Ye Lee, Kyon
Endocrinology and Metabolism.2025; 40(3): 307. 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

Brief Report

Diabetes, obesity and metabolism
Partial Deletion of Perk Improved High-Fat Diet-Induced Glucose Intolerance in Mice: Jooyeop Lee, Min Joo Kim, Seoil Moon, Ji Yoon Lim, Kyong Soo Park, Hye Seung Jung; Endocrinol Metab. 2023;38(6):782-787. Published online November 13, 2023; DOI: https://doi.org/10.3803/EnM.2023.1738

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Abstract PDF Supplementary Material PubReader ePub: Although pancreatic endoplasmic reticulum kinase (PERK) is indispensable to beta cells, low-dose PERK inhibitor improved glucose- stimulated insulin secretion (GSIS) and hyperglycemia in diabetic mice. Current study examined if partial deletion of Perk (Perk^+/-) recapitulated the effects of PERK inhibitor, on the contrary to the complete deletion. Perk^+/- mice and wild-type controls were fed with a high-fat diet (HFD) for 23 weeks. Glucose tolerance was evaluated along with serum insulin levels and islet morphology. Perk^+/- mice on normal chow were comparable to wild-type mice in various metabolic features. HFD-induced obesity was not influenced by Perk reduction; however, HFD-induced glucose intolerance was significantly improved since 15-week HFD. HFD-induced compromises in GSIS were relieved by Perk reduction, accompanied by reductions in phosphorylated PERK and activating transcription factor 4 (ATF4) in the islets. Meanwhile, HFD-induced islet expansion was not significantly affected. In summary, partial deletion of Perk improved glucose tolerance and GSIS impaired by diet-induced obesity, without changes in body weights or islet mass.

Original Articles

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
Tingkat Keberhasilan Terapi Radioiodin Pertama pada Pasien Graves’ Disease
Aliya Khadijah Kemaleratu, Yuliana Rahmah Retnaningrum, Yudanti Riastiti
Jurnal Sains dan Kesehatan.2025; 6(1): 1. CrossRef
Association of high‐dose radioactive iodine therapy with PPM1D‐mutated clonal hematopoiesis in older individuals
Jaeryuk Kim, Sungwoo Bae, Jaeyong Choi, Sun‐Wha Im, Bukyoung Cha, Gyeongseo Jung, Sun Wook Cho, Eul‐Ju Seo, Young Ah Lee, Jin Chul Paeng, Young Joo Park, Jong‐Il Kim
Molecular Oncology.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

Thyroid
Comparison of Korean vs. American Thyroid Imaging Reporting and Data System in Malignancy Risk Assessment of Indeterminate Thyroid Nodules: Sunyoung Kang, Seul Ki Kwon, Hoon Sung Choi, Min Joo Kim, Young Joo Park, Do Joon Park, Sun Wook Cho; Endocrinol Metab. 2021;36(5):1111-1120. Published online October 21, 2021; DOI: https://doi.org/10.3803/EnM.2021.1208

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Background
The management of cytologically indeterminate thyroid nodules is challenging for clinicians. This study aimed to compare the diagnostic performance of the Korean Thyroid Imaging Reporting and Data Systems (K-TIRADS) with that of the American College of Radiology (ACR)-TIRADS for predicting the malignancy risk of indeterminate thyroid nodules.
Methods
Thyroid nodules diagnosed by fine-needle aspiration (FNA) followed by surgery or core needle biopsy at a single referral hospital were enrolled.
Results
Among 200 thyroid nodules, 78 (39.0%) nodules were classified as indeterminate by FNA (Bethesda category III, IV, and V), and 114 (57.0%) nodules were finally diagnosed as malignancy by surgery or core needle biopsy. The area under the curve (AUC) was higher for FNA than for either TIRADS system in all nodules, while all three methods showed similar AUCs for indeterminate nodules. However, for Bethesda category III nodules, applying K-TIRADS 5 significantly increased the risk of malignancy compared to a cytological examination alone (50.0% vs. 26.5%, P=0.028), whereas applying ACR-TIRADS did not lead to a change.
Conclusion
K-TIRADS and ACR-TIRADS showed similar diagnostic performance in assessing indeterminate thyroid nodules, and K-TIRADS had beneficial effects for malignancy prediction in Bethesda category III nodules.

Citations

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Is the nodule location a predictive risk factor for cancer in AUS/FLUS thyroid nodules? A retrospective cohort study
Saad M. Alqahtani, Bassam A. Altalhi, Yousef S. Alalawi, Saif S. Al-Sobhi
Asian Journal of Surgery.2024; 47(6): 2574. CrossRef
Correlation between Ultrasound TI-RADS and Bethesda FNAC Scoring in Thyroid Lesions: A Retrospective Analysis
Smriti Mathur, Amit Chail, Amit K. Das, Seerat Pal, Ranjit S. Lahel
Medical Journal of Dr. D.Y. Patil Vidyapeeth.2024; 17(3): 533. CrossRef
Diagnostic Performance of Various Ultrasound Risk Stratification Systems for Benign and Malignant Thyroid Nodules: A Meta-Analysis
Ji-Sun Kim, Byung Guk Kim, Gulnaz Stybayeva, Se Hwan Hwang
Cancers.2023; 15(2): 424. CrossRef
The impact of thyroid imaging reporting and data system on the management of Bethesda III thyroid nodules
Saad M. Alqahtani, Saif S. Al-Sobhi, Mohammed A. Alturiqy, Riyadh I. Alsalloum, Hindi N. Al-Hindi
Journal of Taibah University Medical Sciences.2023; 18(3): 506. CrossRef
Diagnostic Performance of Six Ultrasound Risk Stratification Systems for Thyroid Nodules: A Systematic Review and Network Meta-Analysis
Do Hyun Kim, Sung Won Kim, Mohammed Abdullah Basurrah, Jueun Lee, Se Hwan Hwang
American Journal of Roentgenology.2023; 220(6): 791. CrossRef
Diagnostic efficiency among Eu-/C-/ACR-TIRADS and S-Detect for thyroid nodules: a systematic review and network meta-analysis
Longtao Yang, Cong Li, Zhe Chen, Shaqi He, Zhiyuan Wang, Jun Liu
Frontiers in Endocrinology.2023;[Epub] CrossRef
Comparison of diagnostic performance of two ultrasound risk stratification systems for thyroid nodules: a systematic review and meta-analysis
Yun Jin Kang, Hee Sun Ahn, Gulnaz Stybayeva, Ju Eun Lee, Se Hwan Hwang
La radiologia medica.2023; 128(11): 1407. CrossRef
Diagnostic Performance of ACR and Kwak TI-RADS for Benign and Malignant Thyroid Nodules: An Update Systematic Review and Meta-Analysis
Yun Jin Kang, Gulnaz Stybayeya, Ju Eun Lee, Se Hwan Hwang
Cancers.2022; 14(23): 5961. CrossRef
Comparison of Thyroid Imaging Reporting and Data Systems in Malignancy Risk Stratification of Indeterminate Thyroid Nodules
Bo Hyun Kim
Endocrinology and Metabolism.2021; 36(5): 974. CrossRef

Endocrine Research
DEHP Down-Regulates Tshr Gene Expression in Rat Thyroid Tissues and FRTL-5 Rat Thyrocytes: A Potential Mechanism of Thyroid Disruption: Min Joo Kim, Hwan Hee Kim, Young Shin Song, Ok-Hee Kim, Kyungho Choi, Sujin Kim, Byung-Chul Oh, Young Joo Park; Endocrinol Metab. 2021;36(2):447-454. Published online March 31, 2021; DOI: https://doi.org/10.3803/EnM.2020.920

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Background
Di-2-ethylhexyl phthalate (DEHP) is known to disrupt thyroid hormonal status. However, the underlying molecular mechanism of this disruption is unclear. Therefore, we investigated the direct effects of DEHP on the thyroid gland.
Methods
DEHP (vehicle, 50 mg/kg, and 500 mg/kg) was administered to Sprague-Dawley rats for 2 weeks. The expression of the thyroid hormone synthesis pathway in rat thyroid tissues was analyzed through RNA sequencing analysis, quantitative reverse transcription-polymerase chain reaction (RT-PCR), and immunohistochemical (IHC) staining. DEHP was treated to FRTL-5 rat thyroid cells, and an RT-PCR analysis was performed. A reporter gene assay containing the promoter of thyroid stimulating hormone receptor (TSHR) in Nthy-ori 3-1 human thyroid cells was constructed, and luciferase activity was determined.
Results
After DEHP treatment, the free thyroxine (T4) and total T4 levels in rats significantly decreased. RNA sequencing analysis of rat thyroid tissues showed little difference between vehicle and DEHP groups. In the RT-PCR analysis, Tshr expression was significantly lower in both DEHP groups (50 and 500 mg/kg) compared to that in the vehicle group, and IHC staining showed that TSHR expression in the 50 mg/kg DEHP group significantly decreased. DEHP treatment to FRTL-5 cells significantly down-regulated Tshr expression. DEHP treatment also reduced luciferase activity in a reporter gene assay for TSHR.
Conclusion
Although overall genetic changes in the thyroid hormone synthesis pathway are not clear, DEHP exposure could significantly down-regulate Tshr expression in thyroid glands. Down-regulation of Tshr gene appears to be one of potential mechanisms of thyroid disruption by DEHP exposure.

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Neonatal exposure to phthalates and their alternatives and associated thyroid disorders: Levels, potential health risks, and mechanisms
Yuting Chen, Xueyu Weng, Yu Hu, Jia Yin, Shuang Liu, Qingqing Zhu, Ligang Hu, Chunyang Liao, Guibin Jiang
Journal of Environmental Sciences.2025; 156: 519. CrossRef
Polystyrene Microplastics‐Induced Thyroid Dysfunction in Mice: A Study of Gene Expression, Oxidative Stress, and Histopathological Changes
Md. Sadequl Islam, Md. Kamruzzaman, Umme Kulsum Rima
Veterinary Medicine and Science.2025;[Epub] CrossRef
ARTS is essential for di-2-ethylhexyl phthalate (DEHP)-induced apoptosis of mouse Leydig cells
Yue Li, Linlin Xu, Chaoju Hao, Si Yang, Jinglei Wang, Jiaxiang Chen
Ecotoxicology and Environmental Safety.2024; 270: 115882. CrossRef
Thyroid dysfunction caused by exposure to environmental endocrine disruptors and the underlying mechanism: A review
Jie He, Jie Xu, Mucong Zheng, Kai Pan, Lilin Yang, Lina Ma, Chuyang Wang, Jie Yu
Chemico-Biological Interactions.2024; 391: 110909. CrossRef
Maternal Thyroid Hormones as Mediators between Phthalate Exposure and Neonatal Birth Weight: A Cross-Sectional Study from the Zunyi Birth Cohort
Lin Tao, Dengqing Liao, Shimin Xiong, Lulu Dai, Yuan-zhong Zhou, Xubo Shen
Environment & Health.2024; 2(11): 816. CrossRef
Thyroid under Attack: The Adverse Impact of Plasticizers, Pesticides, and PFASs on Thyroid Function
Vinicius Gonçalves Rodrigues, Guilherme Henrique, Érica Kássia Sousa-Vidal, Rafaela Martins Miguel de Souza, Evelyn Franciny Cardoso Tavares, Nathana Mezzalira, Thacila de Oliveira Marques, Bruna Monteiro Alves, João Anthony Araújo Pinto, Luana Naomi Niwa
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Intrauterine exposure to di(2-ethylhexyl) phthalate (DEHP) disrupts the function of the hypothalamus-pituitary-thyroid axis of the F1 rats during adult life
Érica Kássia Sousa-Vidal, Guilherme Henrique, Renata Elen Costa da Silva, Caroline Serrano-Nascimento
Frontiers in Endocrinology.2023;[Epub] CrossRef
Drinking water disinfection byproduct iodoacetic acid affects thyroid hormone synthesis in Nthy-ori 3–1 cells
Jingyi Xiao, Yujie Sha, Yuwen Huang, Kunling Long, Huan Wu, Yan Mo, Qiyuan Yang, Shengkun Dong, Qiang Zeng, Xiao Wei
Ecotoxicology and Environmental Safety.2023; 257: 114926. CrossRef
Assessment of five typical environmental endocrine disruptors and thyroid cancer risk: a meta-analysis
Yuyao Yang, Xiaoyue Bai, Juan Lu, Ronghao Zou, Rui Ding, Xiaohui Hua
Frontiers in Endocrinology.2023;[Epub] CrossRef
Investigation of the effects of phthalates on in vitro thyroid models with RNA-Seq and ATAC-Seq
Marta Nazzari, Mírian Romitti, Duncan Hauser, Daniel J. Carvalho, Stefan Giselbrecht, Lorenzo Moroni, Sabine Costagliola, Florian Caiment
Frontiers in Endocrinology.2023;[Epub] CrossRef
Di(2-ethylhexyl) phthalate (DEHP) and thyroid: biological mechanisms of interference and possible clinical implications
Xueting Zhang, Wen Qi, Qi Xu, Xu Li, Liting Zhou, Lin Ye
Environmental Science and Pollution Research.2022; 29(2): 1634. CrossRef
The possible thyroid disruptive effect of di-(2-ethyl hexyl) phthalate and the potential protective role of selenium and curcumin nanoparticles: a toxicological and histological study
Naima Abd El-Halim Sherif, Asmaa El-Banna, Rehab Ahmed Abdel-Moneim, Zahraa Khalifa Sobh, Manal Ibrahim Fathy Balah
Toxicology Research.2022; 11(1): 108. CrossRef
Environmental disruption of reproductive rhythms
Marie-Azélie Moralia, Clarisse Quignon, Marine Simonneaux, Valérie Simonneaux
Frontiers in Neuroendocrinology.2022; 66: 100990. CrossRef
Endocrine-disruptor endpoints in the ovary and thyroid of adult female rats exposed to realistic doses of di-(2-ethylhexyl) phthalate
Amel Jebara, Asma Beltifa, Guissepa Di Bella, Lotfi Mabrouk, Hedi Ben Mansour
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Gang Wei, Cao-xu Zhang, Yu Jing, Xia Chen, Huai-dong Song, Liu Yang
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Role of estrogen receptors in thyroid toxicity induced by mono (2-ethylhexyl) phthalate via endoplasmic reticulum stress: An in vitro mechanistic investigation
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Clinical Study
Low Predictive Value of FRAX Adjusted by Trabecular Bone Score for Osteoporotic Fractures in Korean Women: A Community-Based Cohort Study: Hana Kim, Jung Hee Kim, Min Joo Kim, A Ram Hong, HyungJin Choi, EuJeong Ku, Ji Hyun Lee, Chan Soo Shin, Nam H. Cho; Endocrinol Metab. 2020;35(2):359-366. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.359

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Background
The value of the Fracture Risk Assessment Tool (FRAX) and the trabecular bone score (TBS) for assessing osteoporotic fracture risk has not been fully elucidated in Koreans. We conducted this study to clarify the predictive value of FRAX adjusted by TBS for osteoporotic fractures in Korean women.
Methods
After screening 7,192 eligible subjects from the Ansung cohort, 1,165 women aged 45 to 76 years with available bone mineral density (BMD) and TBS data were enrolled in this study. We assessed their clinical risk factors for osteoporotic fractures and evaluated the predictive value of FRAX with or without BMD and TBS.
Results
During the mean follow-up period of 7.5 years, 99 (8.5%) women suffered major osteoporotic fractures (MOFs) and 28 (2.4%) experienced hip fractures. FRAX without BMD, BMD-adjusted FRAX, and TBS-adjusted FRAX were significantly associated with the risk of MOFs (hazard ratio [HR] per percent increase, 1.08; 95% confidence interval [CI], 1.03 to 1.14; HR, 1.09; 95% CI, 1.03 to 1.15; and HR, 1.07; 95% CI, 1.02 to 1.13, respectively). However, BMD-adjusted FRAX and TBS-adjusted FRAX did not predict MOFs better than FRAX without BMD based on the Harrell’s C statistic. FRAX probabilities showed limited value for predicting hip fractures. The cut-off values of FRAX without BMD, FRAX with BMD, and FRAX with BMD adjusted by TBS for predicting MOFs were 7.2%, 5.0%, and 6.7%, respectively.
Conclusion
FRAX with BMD and TBS adjustment did not show better predictive value for osteoporotic fractures in this study than FRAX without adjustment. Moreover, the cut-off values of FRAX probabilities for treatment might be lower in Korean women than in other countries.

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Review Article

Thyroid
Bisphenols and Thyroid Hormone: Min Joo Kim, Young Joo Park; Endocrinol Metab. 2019;34(4):340-348. Published online December 23, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.4.340

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Abstract PDF PubReader ePub

In recent decades, attention has been directed toward the effects of bisphenol A (BPA) on human health. BPA has estrogenic activity and is regarded as a representative endocrine disruptor. In addition, mounting evidence indicates that BPA can disrupt thyroid hormone and its action. This review examined human epidemiological studies to investigate the association between BPA exposure and thyroid hormone levels, and analyzed in vivo and in vitro experiments to identify the causal relationship and its mechanism of action. BPA is involved in thyroid hormone action not only as a thyroid hormone receptor antagonist, but also through several other mechanisms. Since the use of bisphenols other than BPA has recently increased, we also reviewed the effects of other bisphenols on thyroid hormone action.

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Original Article

Clinical Study
Postoperative Thyroid-Stimulating Hormone Levels Did Not Affect Recurrence after Thyroid Lobectomy in Patients with Papillary Thyroid Cancer: Myung-Chul Lee, Min Joo Kim, Hoon Sung Choi, Sun Wook Cho, Guk Haeng Lee, Young Joo Park, Do Joon Park; Endocrinol Metab. 2019;34(2):150-157. Published online May 10, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.2.150

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Background

Thyroid-stimulating hormone (TSH) suppression is recommended for patients who undergo thyroidectomy for differentiated thyroid cancer (DTC). However, the impact of TSH suppression on clinical outcomes in low-risk DTC remains uncertain. Therefore, we investigated the effects of postoperative TSH levels on recurrence in patients with low-risk DTC after thyroid lobectomy.

Methods

Patients (n=1,528) who underwent thyroid lobectomy for papillary thyroid carcinoma between 2000 and 2012 were included in this study. According to the mean and dominant TSH values during the entire follow-up period or 5 years, patients were divided into four groups (<0.5, 0.5 to 1.9, 2.0 to 4.4, and ≥4.5 mIU/L). Recurrence-free survival was compared among the groups.

Results

During the 5.6 years of follow-up, 21 patients (1.4%) experienced recurrence. Mean TSH levels were within the recommended low-normal range (0.5 to 1.9 mIU/L) during the total follow-up period or 5 years in 38.1% or 36.0% of patients. The mean and dominant TSH values did not affect recurrence-free survival. Adjustment for other risk factors did not alter the results.

Conclusion

Serum TSH levels did not affect short-term recurrence in patients with low-risk DTC after thyroid lobectomy. TSH suppression should be conducted more selectively.

Citations

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Corrigendum

Miscellaneous
Corrigendum: Author's Name Correction. Study Protocol of Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro): Jae Hoon Moon, Ji-hoon Kim, Eun Kyung Lee, Kyu Eun Lee, Sung Hye Kong, Yeo Koon Kim, Woo-Jin Jeong, Chang Yoon Lee, Roh-Eul Yoo, Yul Hwangbo, Young Shin Song, Min Joo Kim, Sun Wook Cho, Su-jin Kim, Eun-Jae Chung, June Young Choi, Chang Hwan Ryu, You Jin Lee, Jeong Hun Hah, Yuh-Seog Jung, Junsun Ryu, Yunji Hwang, Sue K. Park, Ho Kyung Sung, Ka Hee Yi, Do Joon Park, Young Joo Park; Endocrinol Metab. 2018;33(3):427. Published online August 14, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.3.427

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Citations

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Original Articles

Thyroid
Study Protocol of Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro): Jae Hoon Moon, Ji-hoon Kim, Eun Kyung Lee, Kyu Eun Lee, Sung Hye Kong, Yeo Koon Kim, Woo-jin Jung, Chang Yoon Lee, Roh-Eul Yoo, Yul Hwangbo, Young Shin Song, Min Joo Kim, Sun Wook Cho, Su-jin Kim, Eun Jae Jung, June Young Choi, Chang Hwan Ryu, You Jin Lee, Jeong Hun Hah, Yuh-Seog Jung, Junsun Ryu, Yunji Hwang, Sue K. Park, Ho Kyung Sung, Ka Hee Yi, Do Joon Park, Young Joo Park; Endocrinol Metab. 2018;33(2):278-286. Published online June 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.2.278

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Background

The ongoing Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) aims to observe the natural course of papillary thyroid microcarcinoma (PTMC), develop a protocol for active surveillance (AS), and compare the long-term prognosis, quality of life, and medical costs between the AS and immediate surgery groups.

Methods

This multicenter prospective cohort study of PTMC started in June 2016. The inclusion criteria were suspicious of malignancy or malignancy based on fine needle aspiration or core needle biopsy, age of ≥18 years, and a maximum diameter of ≤1 cm. If there was no major organ involvement, no lymph node/distant metastasis, and no variants with poor prognosis, the patients were explained of the pros and cons of immediate surgery and AS before selecting AS or immediate surgery. Follow-up visits (physical examination, ultrasonography, thyroid function, and questionnaires) are scheduled every 6 months during the first 2 years, and then every 1 year thereafter. Progression was defined as a maximum diameter increase of ≥3, ≥2 mm in two dimensions, suspected organ involvement, or lymph node/distant metastasis.

Results

Among 439 enrolled patients, 290 patients (66.1%) chose AS and 149 patients (33.9%) chose immediate surgery. The median follow-up was 6.7 months (range, 0.2 to 11.9). The immediate surgery group had a larger maximum tumor diameter, compared to the AS group (7.1±1.9 mm vs. 6.6±2.0 mm, respectively; P=0.014).

Conclusion

The results will be useful for developing an appropriate PTMC treatment policy based on its natural course and risk factors for progression.

Citations

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Association of Patient Age With Progression of Low-risk Papillary Thyroid Carcinoma Under Active Surveillance
Alexandra Koshkina, Rouhi Fazelzad, Iwao Sugitani, Akira Miyauchi, Lehana Thabane, David P. Goldstein, Sangeet Ghai, Anna M. Sawka
JAMA Otolaryngology–Head & Neck Surgery.2020; 146(6): 552. CrossRef
Active surveillance in low risk papillary thyroid carcinoma
Fabian Pitoia, Anabella Smulever
World Journal of Clinical Oncology.2020; 11(6): 320. CrossRef
Early Diagnosis of Low-Risk Papillary Thyroid Cancer Results Rather in Overtreatment Than a Better Survival
Jolanta Krajewska, Aleksandra Kukulska, Malgorzata Oczko-Wojciechowska, Agnieszka Kotecka-Blicharz, Katarzyna Drosik-Rutowicz, Malgorzata Haras-Gil, Barbara Jarzab, Daria Handkiewicz-Junak
Frontiers in Endocrinology.2020;[Epub] CrossRef
The dilemma of papillary thyroid microcarcinoma management. To operate or not to operate, that is the question
Juan C Galofré
Endocrinología, Diabetes y Nutrición.2019; 66(8): 469. CrossRef
Computed Tomography for Detecting Cervical Lymph Node Metastasis in Patients Who Have Papillary Thyroid Microcarcinoma with Tumor Characteristics Appropriate for Active Surveillance
Dong-Hwa Lee, Yeo Koon Kim, Hyeong Won Yu, June Young Choi, So Yeon Park, Jae Hoon Moon
Thyroid.2019; 29(11): 1653. CrossRef
The dilemma of papillary thyroid microcarcinoma management. To operate or not to operate, that is the question
Juan C Galofré
Endocrinología, Diabetes y Nutrición (English ed.).2019; 66(8): 469. CrossRef
Longitudinal Assessment of Quality of Life According to Treatment Options in Low-Risk Papillary Thyroid Microcarcinoma Patients: Active Surveillance or Immediate Surgery (Interim Analysis of MAeSTro)
Sung Hye Kong, Junsun Ryu, Min Joo Kim, Sun Wook Cho, Young Shin Song, Ka Hee Yi, Do Joon Park, Yul Hwangbo, You Jin Lee, Kyu Eun Lee, Su-jin Kim, Woo-Jin Jeong, Eun-Jae Chung, Jeong Hun Hah, June Young Choi, Chang Hwan Ryu, Yuh-Seog Jung, Jae Hoon Moon,
Thyroid.2019; 29(8): 1089. CrossRef
Ultrasound-guided percutaneous laser ablation for papillary thyroid microcarcinoma: a retrospective analysis of 37 patients
Lili Ji, Qin Wu, Jun Gu, Xuedong Deng, Wei Zhou, Xing Fan, Feng Zhou
Cancer Imaging.2019;[Epub] CrossRef
Evolving management considerations in active surveillance for micropapillary thyroid carcinoma
Allen S. Ho, Irene Chen, Michelle Melany, Wendy L. Sacks
Current Opinion in Endocrinology, Diabetes & Obesity.2018; 25(5): 353. CrossRef

Thyroid
Star-Shaped Intense Uptake of ¹³¹I on Whole Body Scans Can Reflect Good Therapeutic Effects of Low-Dose Radioactive Iodine Treatment of 1.1 GBq: Sung Hye Kong, Jung Ah Lim, Young Shin Song, Shinje Moon, Ye An Kim, Min Joo Kim, Sun Wook Cho, Jae Hoon Moon, Ka Hee Yi, Do Joon Park, Bo Youn Cho, Young Joo Park; Endocrinol Metab. 2018;33(2):228-235. Published online May 4, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.2.228

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Abstract PDF PubReader ePub

Background

After initial radioactive iodine (RAI) treatment in differentiated thyroid cancer patients, we sometimes observe a star-shaped region of intense uptake of ¹³¹I on whole body scans (WBSs), called a ‘star artifact.’ We evaluated the clinical implications of star artifacts on the success rate of remnant ablation and long-term prognosis.

Methods

Total 636 patients who received ¹³¹I dose of 1.1 GBq for the initial RAI therapy and who did not show distant metastasis at the time of diagnosis were retrospectively evaluated. A negative second WBS was used for evaluating the ablation efficacy of the RAI therapy. Among them, 235 patients (36.9%) showed a star artifact on their first WBS.

Results

In patients with first stimulated thyroglobulin (sTg) levels ≤2 ng/mL, patients with star artifacts had a higher rate of negative second WBS compared with those without star artifacts (77.8% vs. 63.9%, P=0.044), and showed significantly higher recurrence-free survival (P=0.043) during the median 8.0 years (range, 1.0 to 10.0) of follow-up. The 5- and 10-year recurrence rates (5YRR, 10YRR) were also significantly lower in patients with star artifacts compared with those without (0% vs. 4.9%, respectively, P=0.006 for 5YRR; 0% vs. 6.4%, respectively, P=0.005 for 10YRR). However, ablation success rate or recurrence-free survival was not different among patients whose first sTg levels >2 ng/mL regardless of star artifacts.

Conclusion

Therefore, star artifacts at initial RAI therapy imply a good ablation efficacy or a favorable long-term prognosis in patients with sTg levels ≤2 ng/mL.

Citations

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Prognostic value of star-shaped intense uptake of 131I in thyroid cancer patients
Liu Xiao, Wen Jie Zhang, Yue Qi Wang, Lin Li
Revista Española de Medicina Nuclear e Imagen Molecular (English Edition).2021; 40(1): 30. CrossRef
Valores pronósticos de la captación en estrella de 131I en pacientes con cáncer diferenciado de tiroides
L. Xiao, W.J. Zhang, Y.Q. Wang, L. Li
Revista Española de Medicina Nuclear e Imagen Molecular.2021; 40(1): 30. CrossRef
Comparison between planar and single-photon computed tomography images for radiation intensity quantification in iodine-131 scintigraphy
Yusuke Iizuka, Tomohiro Katagiri, Minoru Inoue, Kiyonao Nakamura, Takashi Mizowaki
Scientific Reports.2021;[Epub] CrossRef

Obesity and Metabolism
Mitochondrial Complexes I and II Are More Susceptible to Autophagy Deficiency in Mouse β-Cells: Min Joo Kim, Ok Kyong Choi, Kyung Sil Chae, Min Kyeong Kim, Jung Hee Kim, Masaaki Komatsu, Keiji Tanaka, Hakmo Lee, Sung Soo Chung, Soo Heon Kwak, Young Min Cho, Kyong Soo Park, Hye Seung Jung; Endocrinol Metab. 2015;30(1):65-70. Published online March 27, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.1.65

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Background

Damaged mitochondria are removed by autophagy. Therefore, impairment of autophagy induces the accumulation of damaged mitochondria and mitochondrial dysfunction in most mammalian cells. Here, we investigated mitochondrial function and the expression of mitochondrial complexes in autophagy-related 7 (Atg7)-deficient β-cells.

Methods

To evaluate the effect of autophagy deficiency on mitochondrial function in pancreatic β-cells, we isolated islets from Atg7^F/F:RIP-Cre+ mice and wild-type littermates. Oxygen consumption rate and intracellular adenosine 5'-triphosphate (ATP) content were measured. The expression of mitochondrial complex genes in Atg7-deficient islets and in β-TC6 cells transfected with siAtg7 was measured by quantitative real-time polymerase chain reaction.

Results

Baseline oxygen consumption rate of Atg7-deficient islets was significantly lower than that of control islets (P<0.05). Intracellular ATP content of Atg7-deficient islets during glucose stimulation was also significantly lower than that of control islets (P<0.05). By Oxygraph-2k analysis, mitochondrial respiration in Atg7-deficient islets was significantly decreased overall, although state 3 respiration and responses to antimycin A were unaffected. The mRNA levels of mitochondrial complexes I, II, III, and V in Atg7-deficient islets were significantly lower than in control islets (P<0.05). Down-regulation of Atg7 in β-TC6 cells also reduced the expression of complexes I and II, with marginal significance (P<0.1).

Conclusion

Impairment of autophagy in pancreatic β-cells suppressed the expression of some mitochondrial respiratory complexes, and may contribute to mitochondrial dysfunction. Among the complexes, I and II seem to be most vulnerable to autophagy deficiency.

Citations

Citations to this article as recorded by

A Cholecystokinin Analogue Ameliorates Cognitive Deficits and Regulates Mitochondrial Dynamics via the AMPK/Drp1 Pathway in APP/PS1 Mice
L. Hao, M. Shi, J. Ma, S. Shao, Y. Yuan, J. Liu, Z. Yu, Zhenqiang Zhang, Christian Hölscher, Zijuan Zhang
The Journal of Prevention of Alzheimer's Disease.2024; 11(2): 382. CrossRef
Proteomic pathways to metabolic disease and type 2 diabetes in the pancreatic islet
Belinda Yau, Sheyda Naghiloo, Alexis Diaz-Vegas, Austin V. Carr, Julian Van Gerwen, Elise J. Needham, Dillon Jevon, Sing-Young Chen, Kyle L. Hoehn, Amanda E. Brandon, Laurence Macia, Gregory J. Cooney, Michael R. Shortreed, Lloyd M. Smith, Mark P. Keller,
iScience.2021; 24(10): 103099. CrossRef
Natural compound oblongifolin C inhibits autophagic flux, and induces apoptosis and mitochondrial dysfunction in human cholangiocarcinoma QBC939 cells
Aiqing Zhang, Wei He, Huimin Shi, Xiaodan Huang, Guozhong Ji
Molecular Medicine Reports.2016; 14(4): 3179. CrossRef
Autophagy deficiency in β cells blunts incretin-induced suppression of glucagon release from α cells
Min Joo Kim, Ok Kyong Choi, Kyung Sil Chae, Hakmo Lee, Sung Soo Chung, Dong-Sik Ham, Ji-Won Kim, Kun-Ho Yoon, Kyong Soo Park, Hye Seung Jung
Islets.2015; 7(5): e1129096. CrossRef

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