Endocrinology and Metabolism

Original Articles

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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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.

Citations

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Shared Decision-Making for Determining Treatment Strategies in Low-Risk Thyroid Cancer: Protocol of a Multicenter Cluster-Randomized Trial (MAeSTro-SDM)
Eun Kyung Lee, Min Joo Kim, Yul Hwangbo, Jae Hoon Moon, Sun Wook Cho, Young Jun Chai, June Young Choi, Yuh-Seog Jung, Kyu Eun Lee, Eun-Jae Chung, Kyungsik Kim, Su-jin Kim, Woochul Kim, Yoo Hyung Kim, Young Ki Lee, Jinsun Jang, Young Shin Song, Ka Hee Yi,
Journal of Korean Medical Science.2026;[Epub] CrossRef
Study Protocol of Expanded Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro-EXP) (Endocrinol Metab 2025;40:236-46, Jae Hoon Moon et al.)
Eun Kyung Lee, Jae Hoon Moon, Young Joo Park
Endocrinology and Metabolism.2025; 40(4): 655. CrossRef
Study Protocol of Expanded Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro-EXP) (Endocrinol Metab 2025;40:236-46, Jae Hoon Moon et al.)
Hoonsung Choi
Endocrinology and Metabolism.2025; 40(4): 653. CrossRef
Habitat imaging combined with multimodal analysis for preoperative risk stratification of papillary thyroid carcinoma
Jia-Wei Feng, You-Long Zhu, Lu Zhang, Yu-Xin Yang, An-Cheng Qin, Shui-Qing Liu, Yong Jiang
Insights into Imaging.2025;[Epub] CrossRef

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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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.

Citations

Citations to this article as recorded by

Clinical characteristics and risk analysis of lymph node metastasis in patients with cN0 differentiated thyroid carcinoma
Meng Wei, Kaipeng Hu, Gaolin Qiu, Qing Lin, Jincan Qian, Yao Lu, Rui Wang
Scientific Reports.2026;[Epub] CrossRef
Diagnosis of recurrent medullary thyroid cancer: Capabilities of PET/CT with ¹⁸F-DOPA
Nikolai A. Ognerubov, Olga O. Mirsalimova
Consilium Medicum.2026; 28(4): 270. CrossRef
The impact of microscopic extrathyroidal extension on the prognosis of medullary thyroid carcinoma: A multicenter cohort study
Beyza Olcay Ozturk, Umran Keskin, Serhat Uysal, Aysa Hacioglu, Seda Karsli, Burak Andac, Umit Nur Ozbay, Hulyanur Sodan, Sebnem Burhan, Coskun Ates, Ugur Avci, Faruk Kilinc, Selvinaz Erol, Merve Catak, Zafer Pekkolay, Gulhan Akbaba, Goknur Yorulmaz, Sakin
Endocrinología, Diabetes y Nutrición.2025; 72(10): 501633. CrossRef
The impact of microscopic extrathyroidal extension on the prognosis of medullary thyroid carcinoma: A multicenter cohort study
Beyza Olcay Ozturk, Umran Keskin, Serhat Uysal, Aysa Hacioglu, Seda Karsli, Burak Andac, Umit Nur Ozbay, Hulyanur Sodan, Sebnem Burhan, Coskun Ates, Ugur Avci, Faruk Kilinc, Selvinaz Erol, Merve Catak, Zafer Pekkolay, Gulhan Akbaba, Goknur Yorulmaz, Sakin
Endocrinología, Diabetes y Nutrición (English ed.).2025; 72(10): 501633. CrossRef
MEDULLARY THYROID CARCINOMA (MTC): A CURRENT REVIEW OF EPIDEMIOLOGY, DIAGNOSIS, AND THERAPY
Szymon Zysiak, Julia Wawerska, Dawid Głaz, Maksymilian Głaz, Natalia Kamińska, Jędrzej Zaguła, Magdalena Stolarczyk, Aleksandra Jagura-Sukiennik, Mateusz Stronczyński, Kacper Wicha
International Journal of Innovative Technologies in Social Science.2025;[Epub] CrossRef

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

Citations to this article as recorded by

Integrative multi-omics refines the molecular subtypes of thyroid cancers and enhances cancer-progression prediction: a retrospective cohort study
Yoo Hyung Kim, Joseph Wang, Jae-Kyung Won, Youngsoo Kim, Sun Wook Cho, Dohyun Han, Young Joo Park
International Journal of Surgery.2026; 112(5): 11987. CrossRef
Impact of Molecular Testing on Surgical Decision-Making in Indeterminate Thyroid Nodules: A Global Meta-Analysis Across Test Generations
Truong Phan-Xuan Nguyen, Andrey Bychkov, Chan Kwon Jung, Kennichi Kakudo, Chanchal Rana
Endocrine Pathology.2026;[Epub] CrossRef
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; 32(7): 4597. CrossRef
Prediction of malignancy risk in Bethesda III nodules: development and validation of multiple machine learning models
Wentian Li, Jiayu Zhu, Ying Wang, Jingxiu Li, Zhonghui Li, Cuicui Wang, Jingli Xue, Peng Zhou, Qingqing He
Frontiers in Endocrinology.2025;[Epub] CrossRef
Inside the Matrix: Integrated Cytology and Molecular Testing of Thyroid FNAC Samples Using a Commercial Synthetic 3D Scaffold
Diana Raluca Streinu, Dana Liana Stoian, Octavian Constantin Neagoe, Mihnea Derban, Paula Diana Ciordas, Catalin Marian
International Journal of Molecular Sciences.2025; 26(22): 11100. CrossRef

Thyroid
Effect of Cigarette Smoking on Thyroid Cancer: Meta-Analysis: Joon-Hyop Lee, Young Jun Chai, Ka Hee Yi; Endocrinol Metab. 2021;36(3):590-598. Published online May 26, 2021; DOI: https://doi.org/10.3803/EnM.2021.954

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Background
Although smoking is generally carcinogenic, its effect on thyroid cancers is still subject to controversy. The purpose of this study was to summarize the role of smoking in relation to thyroid cancer occurrence.
Methods
We performed a meta-analysis of 24 eligible studies: 21 case-control studies and three prospective cohort studies. The summary odds ratio (OR) and 95% confidence interval (CI) of all studies were acquired based on random effect model. Further subgroup analyses were conducted according to gender, histological type of thyroid cancer, and smoking status of patients for the case-control studies.
Results
The summary effect size indicated a negative association of smoking for thyroid cancer (OR, 0.798; 95% CI, 0.681 to 0.935). From the subgroup analyses for the case-control studies, reduced risk of thyroid cancer was observed in both men (OR, 0.734; 95% CI, 0.553 to 0.974) and women (OR, 0.792; 95% CI, 0.700 to 0.897). The protective effect of smoking was observed in studies in which thyroid cancer was limited to differentiated thyroid cancers (DTCs) (OR, 0.798; 95% CI, 0.706 to 0.902).
Conclusion
Our results suggests that smoking may have a protective effect on thyroid cancer, especially on DTCs. Further studies with larger sample sizes should be conducted in elucidating the dose and time dependent effect of smoking on thyroid cancer with specific focus on the types of thyroid cancers.

Citations

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The harmful habits (smoking, alcohol consumption), thyroid cancer and other chronic thyroid diseases risk
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Incidence and risk factors for skin cancer after heart transplantation: a systematic review and meta-analysis
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Cigarette Smoking, Alcohol Consumption, and the Risk of Thyroid Cancer in Japan: The Japan Public Health Center–Based Prospective Study
Marina Tanitame, Manami Inoue, Taiki Yamaji, Motoki Iwasaki, Shoichiro Tsugane, Norie Sawada
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The global burden of pediatric respiratory infections attributable to long-term exposure to fine particulate matters
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Environmental Pollution.2025; 378: 126419. CrossRef
Co-occurrence of follicular thyroid carcinoma and Warthin’s tumor of the parotid gland: a rare case report
Arnab Adak, Anannya Tripathy, Rajdeep Guha, Sukanya Naskar
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Author correction: Association between exposure to particulate matter during pregnancy and birthweight: A systematic review and a meta-analysis of birth cohort studies
Yinwen Ji, Fei Song, Bo Xu, Yining Zhu, Chuncheng Lu, Yankai Xia
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Thyroid cancers reveal significant age- and gender-specific associations in papillary, medullary, and multinodularity types in Ha’il, Saudi Arabia: retrospective analysis
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OBESITY AS A MODIFIABLE DETERMINANT OF THYROID DYSFUNCTION, STRUCTURAL CHANGES, AND THYROID CANCER
Klaudia Baran, Aleksandra Grygorowicz, Michał Ględa, Michał Szyszka, Weronika Radecka, Weronika Kozak, Agnieszka Szreiber, Karol Grela, Karolina Nowacka, Kamil Jabłoński, Anna Woźniak
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Salman Khazaei, Soheil Abdollahi Yeganeh, Seyed Ahmad Raza Salim Bahrami, Shiva Borzouei
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N. Hasan, N. A. Nasser, A. D. Hussein, O. A. Mohsein
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Association of dietary manganese intake and the IL1R1 rs3917225 polymorphism with thyroid cancer risk: a prospective cohort study in Korea
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Clinical Study
Efficacy of Intraoperative Neuromonitoring in Reoperation for Recurrent Thyroid Cancer Patients: Jang-il Kim, Su-jin Kim, Zhen Xu, JungHak Kwak, Jong-hyuk Ahn, Hyeong Won Yu, Young Jun Chai, June Young Choi, Kyu Eun Lee; Endocrinol Metab. 2020;35(4):918-924. Published online December 23, 2020; DOI: https://doi.org/10.3803/EnM.2020.778

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Background
The use of intraoperative neuromonitoring (IONM) in thyroid surgery to preserve recurrent laryngeal nerve (RLN) function has been widely accepted. We aimed to evaluate the usefulness of IONM in reoperation for recurrent thyroid cancer patients to help identify the RLN and prevent vocal cord palsy (VCP).
Methods
We analyzed 121 consecutive patients (with IONM group, 48 patients; without IONM group, 73 patients) who underwent reoperation for recurrent thyroid cancer after total thyroidectomy from January 2009 to March 2019 in our institution without VCP due to previous operations. Data including age, sex, number of previous operations, histologic subtype of the malignancy at the initial operation, operation time, RLNs at risk, difficulty of RLN identification, surgical procedure, VCP, and other postoperative complications were reviewed. Vocal cord movement evaluations were performed preoperatively and at 2 weeks postoperatively to evaluate RLN function. In patients with VCP, additional evaluations were performed. VCP exceeding 12 months after surgery was considered permanent VCP.
Results
VCP was observed in six (12.5%) and 16 (21.9%) patients with and without IONM (P=0.189). Transient and permanent VCP were found in three (6.3%) and three (6.3%) patients with IONM (P=0.098 and P=0.982, respectively) versus in 12 (16.4%) and four (5.5%) patients without IONM.
Conclusion
The incidence of transient VCP seems to be lower in reoperations with IONM; however, there was no statistical significances. Further study will be needed to ascertain the efficacy of IONM in reoperation for recurrent thyroid cancer patients.

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Construction and validation of a predictive model for hypothermia complication during endoscopic thyroidectomy for thyroid cancer
Hui Ye, Lu Xia, Tian Zhan, Haiwei Zhang
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Review Article

Thyroid
Can Robotic Thyroidectomy Be Performed Safely in Thyroid Carcinoma Patients?: Young Jun Chai, Kyu Eun Lee, Yeo-Kyu Youn; Endocrinol Metab. 2014;29(3):226-232. Published online September 25, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.3.226

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Since the adoption of the Da Vinci robotic system for remote access thyroid surgery, robotic thyroidectomy (RT) has become a popular surgical option for patients who want to avoid neck scars. Surgeons in South Korea pioneered this surgical technique and have reported successful outcomes. Although many studies have reported that RT is a feasible and safe therapeutic alternative, concerns over the surgical and oncological safety of RT remain. This article reviews the advantages and disadvantages of RT and compares the surgical safety and oncological completeness of RT with conventional open thyroidectomy.

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