Endocrinology and Metabolism

Review Article

Thyroid
Ultrasound Imaging Criteria and Protocols for Active Surveillance of Low-Risk Thyroid Cancer: A Review of International Consensus Guidelines: Ji Ye Lee, Dong Gyu Na; Endocrinol Metab. 2025;40(2):185-194. Published online March 27, 2025; DOI: https://doi.org/10.3803/EnM.2024.2319

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Abstract PDF PubReader ePub: Given the indolent nature and favorable outcomes of papillary thyroid microcarcinoma (PTMC), active surveillance (AS) has been adopted as an alternative management option to immediate surgery. However, the meticulous selection of patients based on individual and tumor-specific characteristics, as well as ultrasound (US) findings, is crucial in AS. Regular US monitoring is performed during AS to detect indicators of tumor progression, such as growth, the emergence of new US features suggestive of gross extrathyroidal extension, and lymph node metastasis. Thus, imaging-based evaluations play a pivotal role in guiding the decision to continue AS or proceed with surgical intervention. This review introduces the Korean Society of Thyroid Radiology (KSThR) guideline for the standardized US imaging of patients with low-risk PTMC under AS, which provide practical recommendations for tumor assessment during the initiation and follow-up phases of AS. This review compared the key features of the KSThR guideline with those of major international guidelines and identified the similarities and differences in imaging methodologies and follow-up strategies. The primary objective of this review is to support the broader implementation of AS and improve outcomes for patients with low-risk PTMC by emphasizing imaging protocols.

Original Articles

Medullary Thyroid Carcinoma Detected by Routine Health Screening Had Better Clinical Outcome and Survival: Ji Hyun Yoo, Da Eun Leem, Bo Ram Kim, Tae Hyuk Kim, Sun Wook Kim, Jae Hoon Chung; Received October 22, 2024 Accepted January 8, 2025 Published online March 5, 2025; DOI: https://doi.org/10.3803/EnM.2024.2214 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
The benefits of early detection in medullary thyroid carcinoma (MTC) are not well established. This study investigates the impact of early detection of MTC on clinical outcomes.
Methods
This retrospective study evaluated 144 patients diagnosed with MTC at Samsung Medical Center between 1995 and 2019, classified as asymptomatic (mostly detected through routine health check-ups, including ultrasonography, calcitonin, or carcinoembryonic antigen levels) and symptomatic. Initial treatment response, final clinical outcomes, and cancer-specific survival were compared.
Results
MTC was diagnosed in 104 (72.2%) asymptomatic and 40 (27.8%) symptomatic patients. The symptomatic group showed a significantly larger primary tumor size, more frequent lateral neck lymph node metastasis, more advanced tumor, node, metastasis (TNM) staging, and higher pre- and postoperative serum calcitonin levels. For initial treatment response, the proportion of excellent responders was significantly higher in the asymptomatic group (71.2% vs. 40.0%), while that of patients with biochemical incomplete response (37.5% vs. 26.9%) and structural incomplete response (22.5% vs. 1.9%) was significantly higher in the symptomatic group (all P<0.001). For the final clinical outcomes, the rate of patients with no evidence of disease was higher in the asymptomatic group (67.3% vs. 30.0%), while the rate of patients with structurally identifiable disease was higher in the symptomatic group (45.0% vs. 7.7%) (P<0.001 for both). The symptomatic group had significantly poorer cancer-specific survival than the asymptomatic group (log-rank P=0.023).
Conclusion
Compared with late diagnosis through symptomatic presentation, early diagnosis in asymptomatic patients results in significantly better initial treatment response, final clinical outcomes, and cancer-specific survival in patients with MTC.

Prognostic Impact of Primary Tumor Size in Papillary Thyroid Carcinoma without Lymph Node Metastasis: Chae A Kim, Hye In Kim, Na Hyun Kim, Tae Yong Kim, Won Bae Kim, Jae Hoon Chung, Min Ji Jeon, Tae Hyuk Kim, Sun Wook Kim, Won Gu Kim; Received October 2, 2024 Accepted January 2, 2025 Published online February 25, 2025; DOI: https://doi.org/10.3803/EnM.2024.2199 [Epub ahead of print]

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Abstract PDF PubReader ePub: Background
We aimed to investigate the prognostic significance of primary tumor size in patients with pT1–T3a N0 M0 papillary thyroid carcinoma (PTC), minimizing the impact of confounding factors.
Methods
A multicenter retrospective study included 5,759 patients with PTC. Those with lymph node metastasis, gross extrathyroidal extension (ETE), and aggressive variants were excluded. Patients were categorized by primary tumor size (≤1, 1.1–2, 2.1–4, and >4 cm) and subdivided based on the presence of microscopic ETE (mETE).
Results
The median age was 48.0 years, and 87.5% were female. The median primary tumor size was 0.7 cm, with mETE identified in 43.7%. The median follow-up was 8.0 years, with an overall recurrent/persistent disease rate of 2.8%. Multivariate analysis identified male sex, larger tumor size, and the presence of mETE as significant prognostic risk factors. The 10-year recurrent/persistent disease rates for tumors ≤1, 1.1–2, 2.1–4, and >4 cm were 2.5%, 4.7%, 11.1%, and 6.0%, respectively. The 2.1–4 cm group had a significantly higher hazard ratio (HR), with the >4 cm group had the highest HR than the ≤1 cm group. Patients with mETE had a higher recurrent/persistent disease rate (4.5%) than those without, with rates by tumor size being 2.6%, 5.6%, 16.7%, and 8.2%.
Conclusion
Larger tumor size and the presence of mETE significantly increased the risk of recurrent/persistent disease in PTC. Patients with pT2–T3a N0 M0 PTC (>2 cm) had a recurrent/persistent disease risk exceeding 5%, warranting vigilant management.

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
Association of the Preoperative Controlling Nutritional Status (CONUT) Score with Clinicopathological Characteristics in Patients with Papillary Thyroid Carcinoma: Doohwa Kim, Myungsoo Im, Soree Ryang, Mijin Kim, Yun Kyung Jeon, Sang Soo Kim, Bo Hyun Kim; Endocrinol Metab. 2024;39(6):856-863. Published online November 15, 2024; DOI: https://doi.org/10.3803/EnM.2024.2006

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Abstract PDF Supplementary Material PubReader ePub: Background
The Controlling Nutritional Status (CONUT) score is an immunonutritional test tool based on serum albumin, total cholesterol, and lymphocyte counts. It has been studied as a simple prognostic predictor for various carcinomas. This study aimed to investigate the association between preoperative CONUT scores and the clinicopathological characteristics in papillary thyroid carcinoma (PTC) patients.
Methods
This study included 2,403 PTC patients who underwent total thyroidectomy between 2012 and 2016 at a single tertiary medical center. The CONUT scores were calculated based on preoperative blood tests. The clinicopathological characteristics were retrospectively reviewed. The patients were categorized by the CONUT score (relatively low, 0–2; relatively high, 3–5).
Results
Among the 2,997 PTC patients who underwent total thyroidectomy at Pusan National University Hospital between 2012 and 2016, those without preoperative blood test were excluded (n=149). Finally 2,403 patients were analyzed after excluding 439 patients taking lipid-lowering drugs and six patients without available T stage data after surgery. Based on the CONUT score, the relatively high score group had a lower body mass index (23.7±3.3 kg/m² vs. 21.9±2.9 kg/m², P<0.001), more advanced T stage (T stage 3/4, 5.9% vs. 11.4%, P=0.045), and higher extrathyroidal extension (2.1% vs. 7.6%, P=0.005).
Conclusion
Patients included in this large, single-center study all had a preoperative CONUT score of 0–5, but this study demonstrated that higher preoperative CONUT scores were significantly associated with advanced T stage and extrathyroidal extension. The CONUT score, which can be easily used in clinical practice, is thought to be helpful in predicting the aggressiveness of PTC.

Thyroid
A Neglected Point: Frailty in Older Adults with Differentiated Thyroid Cancer: Meric Coskun, Esra Cataltepe, Hacer Dogan Varan, Eda Ceker, Yasemin Bektas, Yasemin Kuscu, Mehmet Muhittin Yalcin, Mujde Akturk, Fusun Balos Toruner, Mehmet Ayhan Karakoc, Alev Eroglu Altinova; Endocrinol Metab. 2024;39(6):899-907. Published online November 5, 2024; DOI: https://doi.org/10.3803/EnM.2024.2046

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Abstract PDF PubReader ePub: Background
This study investigated the risk of frailty in older adults with differentiated thyroid cancer (DTC) and the effect of thyroid- stimulating hormone (TSH) levels on frailty.
Methods
This single-center, cross-sectional study included 70 DTC patients aged ≥60 years with stable TSH levels during the previous year while receiving levothyroxine. Frailty was assessed using the fried frailty phenotype (FFP). Anterior thigh muscle thickness was measured by ultrasound, and the sonographic thigh adjustment ratio (STAR) index was calculated. Muscle strength was measured using a hand dynamometer. Physical activity was determined by the physical activity scale for the elderly (PASE).
Results
The median (interquartile range) age and follow-up time were 65 years (62 to 71) and 11 years (7.0 to 14.2), respectively. The median TSH level was 1.10 μIU/mL (0.49 to 1.62), and 58.6% of patients were prefrail/frail. Muscle mass and strength were reduced in 35.7% and 17.2% of patients, respectively. TSH levels were lower in those with prefrailty/frailty (P=0.002), low muscle mass (P=0.014), and low strength (P=0.037) than in their normal counterparts. TSH levels correlated negatively with FFP (P= 0.001) and positively with the STAR index (P=0.034). TSH below 1.325 μIU/mL was associated with an increased frailty risk (area under the curve=0.719; P=0.001). Low TSH, female sex, low handgrip strength, and low PASE leisure time scores emerged as independent predictors of frailty (P<0.05).
Conclusion
Older adults with lower TSH levels due to DTC are at high frailty risk and have low muscle mass and strength. Therefore, TSH targets should be set based on a comprehensive evaluation with consideration of the risk-benefit ratio.

Thyroid
Utilizing Immunoglobulin G4 Immunohistochemistry for Risk Stratification in Patients with Papillary Thyroid Carcinoma Associated with Hashimoto Thyroiditis: Faridul Haq, Gyeongsin Park, Sora Jeon, Mitsuyoshi Hirokawa, Chan Kwon Jung; Endocrinol Metab. 2024;39(3):468-478. Published online May 20, 2024; DOI: https://doi.org/10.3803/EnM.2024.1923

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Background
Hashimoto thyroiditis (HT) is suspected to correlate with papillary thyroid carcinoma (PTC) development. While some HT cases exhibit histologic features of immunoglobulin G4 (IgG4)-related disease, the relationship of HT with PTC progression remains unestablished.
Methods
This cross-sectional study included 426 adult patients with PTC (≥1 cm) undergoing thyroidectomy at an academic thyroid center. HT was identified based on its typical histologic features. IgG4 and IgG immunohistochemistry were performed. Wholeslide images of immunostained slides were digitalized. Positive plasma cells per 2 mm² were counted using QuPath and a pre-trained deep learning model. The primary outcome was tumor structural recurrence post-surgery.
Results
Among the 426 PTC patients, 79 were diagnosed with HT. With a 40% IgG4 positive/IgG plasma cell ratio as the threshold for diagnosing IgG4-related disease, a cutoff value of >150 IgG4 positive plasma cells per 2 mm² was established. According to this criterion, 53% (43/79) of HT patients were classified as IgG4-related. The IgG4-related HT subgroup presented a more advanced cancer stage than the IgG4-non-related HT group (P=0.038). The median observation period was 109 months (range, 6 to 142). Initial assessment revealed 43 recurrence cases. Recurrence-free survival periods showed significant (P=0.023) differences, with patients with IgG4 non-related HT showing the longest period, followed by patients without HT and those with IgG4-related HT.
Conclusion
This study effectively stratified recurrence risk in PTC patients based on HT status and IgG4-related subtypes. These findings may contribute to better-informed treatment decisions and patient care strategies.

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Advanced pathological subtype classification of thyroid cancer using efficientNetB0
Hongpeng Guo, Junjie Zhang, You Li, Xinghe Pan, Chenglin Sun
Diagnostic Pathology.2025;[Epub] CrossRef

Thyroid
Clinicopathological Features and Molecular Signatures of Lateral Neck Lymph Node Metastasis in Papillary Thyroid Microcarcinoma: Jinsun Lim, Han Sai Lee, Jin-Hyung Heo, Young Shin Song; Endocrinol Metab. 2024;39(2):324-333. Published online April 4, 2024; DOI: https://doi.org/10.3803/EnM.2023.1885

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Background
The predictive factors for lateral neck lymph node metastasis (LLNM) in papillary thyroid microcarcinoma (PTMC) remain undetermined. This study investigated the clinicopathological characteristics, transcriptomes, and tumor microenvironment in PTMC according to the LLNM status. We aimed to identify the biomarkers associated with LLNM development.
Methods
We retrospectively reviewed the medical records of patients with PTMC from two independent institutions between 2018 and 2022 (n=597 and n=467). We compared clinicopathological features between patients without lymph node metastasis (N0) and those with LLNM (N1b). Additionally, laser capture microdissection and RNA sequencing were performed on primary tumors from both groups, including metastatic lymph nodes from the N1b group (n=30; 20 primary tumors and 10 paired LLNMs). We corroborated the findings using RNA sequencing data from 16 BRAF-like PTMCs from The Cancer Genome Atlas. Transcriptomic analyses were validated by immunohistochemical staining.
Results
Clinicopathological characteristics, such as male sex, multifocality, extrathyroidal extension, lymphatic invasion, and central node metastasis showed associations with LLNM in PTMCs. Transcriptomic profiles between the N0 and N1b PTMC groups were similar. However, tumor microenvironment deconvolution from RNA sequencing and immunohistochemistry revealed an increased abundance of tumor-associated macrophages, particularly M2 macrophages, in the N1b group.
Conclusion
Patients with PTMC who have a male sex, multifocality, extrathyroidal extension, lymphatic invasion, and central node metastasis exhibited an elevated risk for LLNM. Furthermore, infiltration of M2 macrophages in the tumor microenvironment potentially supports tumor progression and LLNM in PTMCs.

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Prediction of lymph node metastasis in papillary thyroid carcinoma using non-contrast CT-based radiomics and deep learning with thyroid lobe segmentation: A dual-center study
Hao Wang, Xuan Wang, Yusheng Du, You Wang, Zhuojie Bai, Di Wu, Wuliang Tang, Hanling Zeng, Jing Tao, Jian He
European Journal of Radiology Open.2025; 14: 100639. CrossRef

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.

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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
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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
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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
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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
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Jin Hyang Jung, Eunji Kim, Byung Ju Kang
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Systemic therapy for differentiated thyroid cancer with distant metastasis
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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

Original Articles

Thyroid
Active Surveillance for Low-Risk Papillary Thyroid Carcinoma as an Acceptable Management Option with Additional Benefits: A Comprehensive Systematic Review: Jee Hee Yoon, Wonsuk Choi, Ji Yong Park, A Ram Hong, Hee Kyung Kim, Ho-Cheol Kang; Endocrinol Metab. 2024;39(1):152-163. Published online January 22, 2024; DOI: https://doi.org/10.3803/EnM.2023.1794

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Background
Active surveillance (AS) has been introduced as a management strategy for low-risk papillary thyroid carcinoma (PTC) due to its typically indolent nature. Despite this, the widespread adoption of AS has encountered several challenges. The aim of this systematic review was to evaluate the safety of AS related to disease progression and its benefits compared with immediate surgery (IS).
Methods
Studies related to AS in patients with low-risk PTC were searched through the Ovid MEDLINE, Embase, Cochrane Library, and KoreaMed databases. Studies on disease progression, surgical complication, quality of life (QoL), and cost-effectiveness were separately analyzed and narratively synthesized.
Results
In the evaluation of disease progression, the proportions of cases with tumor growth ≥3 mm and a volume increase >50% were 2.2%–10.8% and 16.0%–25.5%, respectively. Newly detected lymph node metastasis was identified in 0.0%–1.4% of patients. No significant difference was found between IS and delayed surgery in surgical complications, including vocal cord paralysis and postoperative hypoparathyroidism. AS was associated with better QoL than IS. Studies on the cost-effectiveness of AS reported inconsistent data, but AS was more cost-effective when quality-adjusted life years were considered.
Conclusion
AS is an acceptable management option for patients with low-risk PTC based on the low rate of disease progression and the absence of an increased mortality risk. AS has additional benefits, including improved QoL and greater QoL-based cost-effectiveness.

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Thyroid Nodules: Past, Present, and Future
Alan A. Parsa, Hossein Gharib
Endocrine Practice.2025; 31(1): 114. CrossRef
Approach to the Patient With Thyroid Cancer: Selection and Management of Candidates for Lobectomy
Eyal Robenshtok, Gideon Bachar, Amit Ritter
The Journal of Clinical Endocrinology & Metabolism.2025;[Epub] 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
It Is Time to Understand the Additional Benefits of Active Surveillance for Low-Risk Papillary Thyroid Carcinoma
Kyeong Jin Kim
Endocrinology and Metabolism.2024; 39(1): 95. CrossRef

Thyroid
Comparative Analysis of Driver Mutations and Transcriptomes in Papillary Thyroid Cancer by Region of Residence in South Korea: Jandee Lee, Seonhyang Jeong, Hwa Young Lee, Sunmi Park, Meesson Jeong, Young Suk Jo; Endocrinol Metab. 2023;38(6):720-729. Published online November 6, 2023; DOI: https://doi.org/10.3803/EnM.2023.1758

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Background
Radiation exposure is a well-known risk factor for papillary thyroid cancer (PTC). South Korea has 24 nuclear reactors in operation; however, no molecular biological analysis has been performed on patients with PTC living near nuclear power plants.
Methods
We retrospectively included patients with PTC (n=512) divided into three groups according to their place of residence at the time of operation: inland areas (n=300), coastal areas far from nuclear power plants (n=134), and nuclear power plant areas (n=78). After propensity score matching (1:1:1) by age, sex, and surgical procedure, the frequency of representative driver mutations and gene expression profiles were compared (n=50 per group). Epithelial-mesenchymal transition (EMT), BRAF, thyroid differentiation, and radiation scores were calculated and compared.
Results
No significant difference was observed in clinicopathological characteristics, including radiation exposure history and the frequency of incidentally discovered thyroid cancer, among the three groups. BRAF^V600E mutation was most frequently detected in the groups, with no difference among the three groups. Furthermore, gene expression profiles showed no statistically significant difference. EMT and BRAF scores were higher in our cohort than in cohorts from Chernobyl tissue bank and The Cancer Genome Atlas Thyroid Cancer; however, there was no difference according to the place of residence. Radiation scores were highest in the Chernobyl tissue bank but exhibited no difference according to the place of residence.
Conclusion
Differences in clinicopathological characteristics, frequency of representative driver mutations, and gene expression profiles were not observed according to patients’ region of residence in South Korea.

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Systemic therapy for differentiated thyroid cancer with distant metastasis
Eun Kyung Lee
Journal of the Korean Medical Association.2024; 67(7): 484. CrossRef

Thyroid
Different Molecular Phenotypes of Progression in BRAF- and RAS-Like Papillary Thyroid Carcinoma: Jinsun Lim, Han Sai Lee, Jiyun Park, Kyung-Soo Kim, Soo-Kyung Kim, Yong-Wook Cho, Young Shin Song; Endocrinol Metab. 2023;38(4):445-454. Published online July 18, 2023; DOI: https://doi.org/10.3803/EnM.2023.1702

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Background
Papillary thyroid carcinoma (PTC) can be classified into two distinct molecular subtypes, BRAF-like (BL) and RASlike (RL). However, the molecular characteristics of each subtype according to clinicopathological factors have not yet been determined. We aimed to investigate the gene signatures and tumor microenvironment according to clinicopathological factors, and to identify the mechanism of progression in BL-PTCs and RL-PTCs.
Methods
We analyzed RNA sequencing data and corresponding clinicopathological information of 503 patients with PTC from The Cancer Genome Atlas database. We performed differentially expressed gene (DEG), Gene Ontology, and molecular pathway enrichment analyses according to clinicopathological factors in each molecular subtype. EcoTyper and CIBERSORTx were used to deconvolve the tumor cell types and their surrounding microenvironment.
Results
Even for the same clinicopathological factors, overlapping DEGs between the two molecular subtypes were uncommon, indicating that BL-PTCs and RL-PTCs have different progression mechanisms. Genes related to the extracellular matrix were commonly upregulated in BL-PTCs with aggressive clinicopathological factors, such as old age (≥55 years), presence of extrathyroidal extension, lymph node metastasis, advanced tumor-node-metastasis (TNM) stage, and high metastasis-age-completeness of resection- invasion-size (MACIS) scores (≥6). Furthermore, in the deconvolution analysis of tumor microenvironment, cancer-associated fibroblasts were significantly enriched. In contrast, in RL-PTCs, downregulation of immune response and immunoglobulin-related genes was significantly associated with aggressive characteristics, even after adjusting for thyroiditis status.
Conclusion
The molecular phenotypes of cancer progression differed between BL-PTC and RL-PTC. In particular, extracellular matrix and cancer-associated fibroblasts, which constitute the tumor microenvironment, would play an important role in the progression of BL-PTC that accounts for the majority of advanced PTCs.

Citations

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Nuclear pseudoinclusion is associated with BRAFV600E mutation: Analysis of nuclear features in papillary thyroid carcinoma
Agnes Stephanie Harahap, Dina Khoirunnisa, Salinah, Maria Francisca Ham
Annals of Diagnostic Pathology.2025; 75: 152434. CrossRef
Transcriptome of Anaplastic Thyroid Cancer Reveals Two Molecular Subtypes with Distinct Tumor Microenvironment and Prognosis
Hyunjong Byun, Han Sai Lee, Young Shin Song, Young Joo Park
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Thyroid
Diagnostic Performance of Thyroid Core Needle Biopsy Using the Revised Reporting System: Comparison with Fine Needle Aspiration Cytology: Kwangsoon Kim, Ja Seong Bae, Jeong Soo Kim, So Lyung Jung, Chan Kwon Jung; Endocrinol Metab. 2022;37(1):159-169. Published online February 28, 2022; DOI: https://doi.org/10.3803/EnM.2021.1299

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Background
We aim to validate the diagnostic performance of thyroid core needle biopsy (CNB) for diagnosing malignancy in clinical settings to align with the changes made in recently updated thyroid CNB guidelines.
Methods
We retrospectively analyzed 1,381 thyroid CNB and 2,223 fine needle aspiration (FNA) samples. The FNA and CNB slides were interpreted according to the Bethesda System for Reporting Thyroid Cytopathology and updated practice guidelines for thyroid CNB, respectively.
Results
Compared to FNA, CNB showed lower rates of inconclusive results: categories I (2.8% vs. 11.2%) and III (1.2% vs. 6.2%), and higher rates of categories II (60.9% vs. 50.4%) and IV (17.5% vs. 2.0%). The upper and lower bounds of the risk of malignancy (ROM) for category IV of CNB were 43.2% and 26.6%, respectively. The CNB subcategory IVb with nuclear atypia had a higher ROM than the subcategory without nuclear atypia (40%–62% vs. 23%–36%). In histologically confirmed cases, there was no significant difference in the diagnostic performance between CNB and FNA for malignancy. However, neoplastic diseases were more frequently detected by CNB than by FNA (88.8% vs. 77.6%, P=0.046). In category IV, there was no difference in unnecessary surgery rate between CNB and FNA (4.7% vs. 6.9%, P=0.6361).
Conclusion
Thyroid CNB decreased the rate of inconclusive results and showed a higher category IV diagnostic rate than FNA. The revised guidelines for thyroid CNB proved to be an excellent reporting system for assessing thyroid nodules.

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Qixin Huang, Zhenhe Chen, Lingyu Zhao, Lichao Jiang, Ye Wang, Qianqian Feng, Yajuan Lei, Xiaodong Li, Dingrong Zhong
Pathology - Research and Practice.2025; 270: 155952. CrossRef
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Thyroid
Clinicopathological Characteristics and Disease-Free Survival in Patients with Hürthle Cell Carcinoma: A Multicenter Cohort Study in South Korea: Meihua Jin, Eun Sook Kim, Bo Hyun Kim, Hee Kyung Kim, Yea Eun Kang, Min Ji Jeon, Tae Yong Kim, Ho-Cheol Kang, Won Bae Kim, Young Kee Shong, Mijin Kim, Won Gu Kim; Endocrinol Metab. 2021;36(5):1078-1085. Published online October 28, 2021; DOI: https://doi.org/10.3803/EnM.2021.1151

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Background
Hürthle cell carcinoma (HCC), a type of thyroid carcinoma, is rare in South Korea, and few studies have investigated its prognosis.
Methods
This long-term multicenter retrospective cohort study evaluated the clinicopathological features and clinical outcomes in patients with HCC who underwent thyroid surgery between 1996 and 2009.
Results
The mean age of the 97 patients included in the study was 50.3 years, and 26.8% were male. The mean size of the primary tumor was 3.2±1.8 cm, and three (3.1%) patients had distant metastasis at initial diagnosis. Ultrasonographic findings were available for 73 patients; the number of nodules with low-, intermediate-, and high suspicion was 28 (38.4%), 27 (37.0%), and 18 (24.7%), respectively, based on the Korean-Thyroid Imaging Reporting and Data System. Preoperatively, follicular neoplasm (FN) or suspicion for FN accounted for 65.2% of the cases according to the Bethesda category, and 13% had malignancy or suspicious for malignancy. During a median follow-up of 8.5 years, eight (8.2%) patients had persistent/recurrent disease, and none died of HCC. Older age, gross extrathyroidal extension (ETE), and widely invasive types of tumors were significantly associated with distant metastasis (all P<0.01). Gross ETE (hazard ratio [HR], 27.7; 95% confidence interval [CI], 2.2 to 346.4; P=0.01) and widely invasive classification (HR, 6.5; 95% CI, 1.1 to 39.4; P=0.04) were independent risk factors for poor disease-free survival (DFS).
Conclusion
The long-term prognosis of HCC is relatively favorable in South Korea from this study, although this is not a nation-wide data, and gross ETE and widely invasive cancer are significant prognostic factors for DFS. The diagnosis of HCC by ultrasonography and cytopathology remains challenging.

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Prognostic impact of fibrosclerotic changes in non-papillary, non-anaplastic, follicular cell-derived thyroid carcinomas
Giulia Orlando, Giulia Capella, Giulia Vocino Trucco, Elena Vissio, Jasna Metovic, Francesca Maletta, Marco Volante, Mauro Papotti
Virchows Archiv.2025;[Epub] CrossRef
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Nelson R. Gruszczynski, Shahzeb S. Hasan, Ana G. Brennan, Julian De La Chapa, Adithya S. Reddy, David N. Martin, Prem P. Batchala, Edward B. Stelow, Eric M. Dowling, Katherine L. Fedder, Jonathan C. Garneau, David C. Shonka
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Xiqian Wang, Yingao Liu, Lijie Chen, Jie Zhang, Ruoyu Jiang, Lei Zhang, Han Yan, Jie Zhang
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Soo Young Kim
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Lu Li, Likun Zhang, Wenhao Jiang, Zhiqiang Gui, Zhihong Wang, Hao Zhang, Yi He, Yi Zhu, Tiannan Guo, Haixia Guan, Zhiyan Liu, Yaoting Sun, Jianqing Gao
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Thyroid
Lobeglitazone, A Peroxisome Proliferator-Activated Receptor-Gamma Agonist, Inhibits Papillary Thyroid Cancer Cell Migration and Invasion by Suppressing p38 MAPK Signaling Pathway: Jun-Qing Jin, Jeong-Sun Han, Jeonghoon Ha, Han-Sang Baek, Dong-Jun Lim; Endocrinol Metab. 2021;36(5):1095-1110. Published online October 14, 2021; DOI: https://doi.org/10.3803/EnM.2021.1155

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Background
Peroxisome proliferator-activated receptor-gamma (PPAR-γ) ligands have been widely shown to correlate with epithelial-mesenchymal transition (EMT) and cancer progression. Lobeglitazone (LGZ) is a novel ligand of PPAR-γ; and its role in EMT and metastasis in papillary thyroid carcinoma (PTC) is poorly understood. We aimed to investigate the role of LGZ in metastatic behavior of PTC cells.
Methods
Half maximal inhibitory concentration (IC₅₀) values of LGZ in BRAF-mutated PTC cell lines (BCPAP and K1) were determined using MTT assay. Rosiglitazone (RGZ), the PPAR-γ ligand was used as a positive control. The protein expression of PPAR-γ, cell-surface proteins (E-cadherin, N-cadherin), cytoskeletal protein (Vimentin), transcription factor (Snail), p38 mitogenactivated protein kinase (MAPK), extracellular signal-regulated kinase (ERK) 1/2 pathway, and matrix metalloproteinase (MMP)-2 expression were measured using Western blotting. Changes in E-cadherin expression were also determined using immunocytochemistry. Cell migration and invasion were analyzed using wound healing and Matrigel invasion assays.
Results
Treatment with LGZ or RGZ significantly inhibited transforming growth factor-beta1 (TGF-β1)-induced EMT-associated processes such as fibroblast-like morphological changes, EMT-related protein expression, and increased cell migration and invasion in BCPAP and K1 cells. LGZ restored TGF-β1-induced loss of E-cadherin, as observed using immunocytochemistry. Furthermore, LGZ and RGZ suppressed TGF-β1-induced MMP-2 expression and phosphorylation of p38 MAPK, but not ERK1/2. Although there was no change in PPAR-γ expression after treatment with LGZ or RGZ, the effect of downstream processes mediated by LGZ was hampered by GW9662, a PPAR-γ antagonist.
Conclusion
LGZ inhibits TGF-β1-induced EMT, migration, and invasion through the p38 MAPK signaling pathway in a PPAR-γ-dependent manner in PTC cells.

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