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

Citations to this article as recorded by

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
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;[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
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.

Hypothalamus and pituitary gland
Preoperative Serum Copeptin Can Predict Delayed Hyponatremia after Pituitary Surgery in the Absence of Arginine Vasopressin Deficiency: Ho Kang, Seung Shin Park, Yoo Hyung Kim, Hwan Sub Lim, Mi-Kyeong Lee, Kyoung-Ryul Lee, Jung Hee Kim, Yong Hwy Kim; Endocrinol Metab. 2024;39(1):164-175. Published online January 3, 2024; DOI: https://doi.org/10.3803/EnM.2023.1792

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Background
Delayed postoperative hyponatremia (DPH) is the most common cause of readmission after pituitary surgery. In this study, we aimed to evaluate the cutoff values of serum copeptin and determine the optimal timing for copeptin measurement for the prediction of the occurrence of DPH in patients who undergo endoscopic transsphenoidal approach (eTSA) surgery and tumor resection.
Methods
This was a prospective observational study of 73 patients who underwent eTSA surgery for pituitary or stalk lesions. Copeptin levels were measured before surgery, 1 hour after extubation, and on postoperative days 1, 2, 7, and 90.
Results
Among 73 patients, 23 patients (31.5%) developed DPH. The baseline ratio of copeptin to serum sodium level showed the highest predictive performance (area under the curve [AUROC], 0.699), and its optimal cutoff to maximize Youden’s index was 2.5×10^–11, with a sensitivity of 91.3% and negative predictive value of 92.0%. No significant predictors were identified for patients with transient arginine vasopressin (AVP) deficiency. However, for patients without transient AVP deficiency, the copeptin-to-urine osmolarity ratio at baseline demonstrated the highest predictive performance (AUROC, 0.725). An optimal cutoff of 6.5×10^–12 maximized Youden’s index, with a sensitivity of 92.9% and a negative predictive value of 94.1%.
Conclusion
The occurrence of DPH can be predicted using baseline copeptin and its ratio with serum sodium or urine osmolarity only in patients without transient AVP deficiency after pituitary surgery.

Citations

Citations to this article as recorded by

Surgical outcomes of endoscopic endonasal surgery for nonfunctioning pituitary adenoma in elderly patients: a comprehensive analysis beyond age
Sun Mo Nam, Jong Ha Hwang, Hye Seok Park, Seung Shin Park, Jung Hee Kim, Min-Sung Kim, Chul-Kee Park, Hee-Pyoung Park, Yong Hwy Kim
BMC Endocrine Disorders.2026;[Epub] CrossRef
Incidence and risk factors of hyponatremia after transsphenoidal surgery: a systematic meta-analysis
Kevin L. Webb, Charles E. Reilly, Mickayla L. Hinkle, Yuki Shinya, Jamie J. Van Gompel, Fredric B. Meyer
Neurosurgical Review.2025;[Epub] CrossRef
Impact Factors of Blood Copeptin Levels in Health and Disease States
Yutong Wang, Shirui Wang, Siyu Liang, Xinke Zhou, Xiaoyuan Guo, Bochuan Huang, Hui Pan, Huijuan Zhu, Shi Chen
Endocrine Practice.2024; 30(12): 1197. 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

Citations to this article as recorded by

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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