Endocrinology and Metabolism

Review Articles

Thyroid
The Initial Risk Stratification System for Differentiated Thyroid Cancer: Key Updates in the 2024 Korean Thyroid Association Guideline: Shinje Moon, Young Shin Song, Kyong Yeun Jung, Eun Kyung Lee, Jeongmin Lee, Dong-Jun Lim, Chan Kwon Jung, Young Joo Park, on Behalf of the Korean Thyroid Association Clinical Guideline Committee; Endocrinol Metab. 2025;40(3):357-384. Published online June 24, 2025; DOI: https://doi.org/10.3803/EnM.2025.2465

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Abstract PDF Supplementary Material PubReader ePub: In 2024, the Korean Thyroid Association (KTA) introduced a revised Risk Stratification System (K-RSS) for differentiated thyroid cancer, building upon the modified RSS (M-RSS) proposed by the American Thyroid Association in 2015. The K-RSS emphasizes the cumulative impact of coexisting clinical and pathological features, acknowledging that multiple intermediate-risk factors collectively indicate a higher recurrence risk. Histologic classification follows the 2022 World Health Organization classification, consolidating encapsulated follicular-patterned thyroid carcinomas, including invasive encapsulated follicular variant papillary thyroid carcinoma, follicular thyroid carcinoma, and oncocytic carcinoma of the thyroid gland, and stratifying them by the extent of capsular and vascular invasion. High-grade thyroid carcinoma is newly included. Updated criteria for tumor size and extrathyroidal extension (ETE) represent another significant change. BRAF^V600E-mutated papillary thyroid carcinomas measuring 1 to 2 cm are now considered lower risk than previously classified in the M-RSS, while encapsulated follicular-patterned tumors larger than 4 cm are considered higher risk. Both minimal ETE and gross ETE confined to the strap muscles have been downgraded to low and intermediate risk, respectively. These changes are accompanied by updates regarding molecular profiling and surgical margin status. Collectively, these updates aim to minimize overtreatment in low-risk patients, while ensuring intensified management for those at higher risk.

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.

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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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
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

Thyroid Big Data Articles (National Health Insurance Service Database)
Risk of Subsequent Primary Cancers in Thyroid Cancer Survivors according to the Dose of Levothyroxine: A Nationwide Cohort Study: Min-Su Kim, Jang Won Lee, Min Kyung Hyun, Young Shin Song; Endocrinol Metab. 2024;39(2):288-299. Published online March 4, 2024; DOI: https://doi.org/10.3803/EnM.2023.1815

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Background
Current research has not investigated the effect of thyroid-stimulating hormone suppression therapy with levothyroxine on the risk for developing subsequent primary cancers (SPCs). This study aimed to investigate the association between levothyroxine dosage and the risk for SPCs in thyroid cancer patients.
Methods
We conducted a nationwide population-based retrospective cohort study form Korean National Health Insurance database. This cohort included 342,920 thyroid cancer patients between 2004 and 2018. Patients were divided into the non-levothyroxine and the levothyroxine groups, the latter consisting of four dosage subgroups according to quartiles. Cox proportional hazard models were performed to evaluate the risk for SPCs by adjusting for variables including cumulative doses of radioactive iodine (RAI) therapy.
Results
A total of 17,410 SPC cases were observed over a median 7.3 years of follow-up. The high-dose levothyroxine subgroups (Q3 and Q4) had a higher risk for SPC (adjusted hazard ratio [HR], 1.14 and 1.27; 95% confidence interval [CI], 1.05–1.24 and 1.17– 1.37; respectively) compared to the non-levothyroxine group. In particular, the adjusted HR of stomach (1.31), colorectal (1.60), liver and biliary tract (1.95), and pancreatic (2.48) cancers were increased in the Q4 subgroup. We consistently observed a positive association between high levothyroxine dosage per body weight and risk of SPCs, even after adjusting for various confounding variables. Moreover, similar results were identified in the stratified analyses according to thyroidectomy type and RAI therapy, as well as in a subgroup analysis of patients with good adherence.
Conclusion
High-dose levothyroxine use was associated with increased risk of SPCs among thyroid cancer patients regardless of RAI therapy.

Citations

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Tailoring TSH suppression in differentiated thyroid carcinoma: evidence, controversies, and future directions
Xinxin Song, Xin Zhi, Linxue Qian
Endocrine.2025; 89(1): 1. CrossRef
The Levothyroxine Odyssey: Navigating the Path of Survivorship in Thyroid Cancer
Jin Hwa Kim
Endocrinology and Metabolism.2024; 39(2): 283. CrossRef
Levothyroxine Dosage and the Increased Risk of Second Primary Malignancy in Thyroid Cancer Survivors
Young Joo Park
Clinical Thyroidology®.2024; 36(7): 258. 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
Journal of Proteome Research.2025; 24(1): 256. CrossRef
Association Between Metabolic Dysfunction-Associated Steatotic Liver Disease and Thyroid Cancer
Sang Yi Moon, Minkook Son, Jung-Hwan Cho, Hye In Kim, Ji Min Han, Ji Cheol Bae, Sunghwan Suh
Thyroid®.2025; 35(1): 79. CrossRef
Navigating Active Surveillance for Low-Risk PTMC by Standardizing Ultrasound Evaluation: Key Takeaways from the Latest Korean Society of Thyroid Radiology Consensus Statements
Young Joo Park
Clinical Thyroidology®.2025; 37(1): 27. CrossRef
Assessing the Rise in Papillary Thyroid Cancer Incidence: A 38-Year Australian Study Investigating WHO Classification Influence
Steven Weller, Cordia Chu, Alfred King-yin Lam
Journal of Epidemiology and Global Health.2025;[Epub] CrossRef
A Personalized, Risk-Based Approach to Active Surveillance for Prostate Cancer with Takeaways from Broader Oncology Practices: A Mixed Methods Review
Jeroen J. Lodder, Sebastiaan Remmers, Roderick C. N. van den Bergh, Arnoud W. Postema, Pim J. van Leeuwen, Monique J. Roobol
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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
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
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2023 Update of the Korean Thyroid Association Guidelines for the Management of Thyroid Nodules
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Jiyun Park, Jin-Hyung Jung, Hyunju Park, Young Shin Song, Soo-Kyung Kim, Yong-Wook Cho, Kyungdo Han, Kyung-Soo Kim
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Prediction of Recurrent Laryngeal Nerve Invasion in Thyroid Cancer by Ultrasound
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Journal of Surgical Ultrasound.2024; 11(1): 18. CrossRef
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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
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Indian Journal of Surgical Oncology.2024;[Epub] CrossRef

Original Articles

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
Thyroid®.2025; 35(4): 367. CrossRef
Allele frequency in thyroid cancer: mechanisms, challenges, and applications in cancer therapy
Jiayu Huang, Jiazhi Wang, Guangzhi Wang, Yongfu Zhao
Thyroid Research.2025;[Epub] CrossRef
Papillary Thyroid Cancer Remodels the Genetic Information Processing Pathways
Dumitru Andrei Iacobas, Sanda Iacobas
Genes.2024; 15(5): 621. CrossRef
A computational approach to assessing the prognostic implications of BRAF and RAS mutations in patients with papillary thyroid carcinoma
Tahereh Haghzad, Babak Khorsand, S. Adeleh Razavi, Mehdi Hedayati
Endocrine.2024; 86(2): 707. CrossRef
Correlation between gene mutations and clinical characteristics in papillary thyroid cancer: a retrospective analysis of BRAF mutations and RET rearrangements
Daisuke Uno, Kazuhira Endo, Tomomi Yoshikawa, Nobuyuki Hirai, Eiji Kobayashi, Yosuke Nakanishi, Satoru Kondo, Tomokazu Yoshizaki
Thyroid Research.2024;[Epub] CrossRef
Multi-objective genetic algorithm for multi-view feature selection
Vandad Imani, Carlos Sevilla-Salcedo, Elaheh Moradi, Vittorio Fortino, Jussi Tohka
Applied Soft Computing.2024; 167: 112332. CrossRef
Emerging Strategies for the Treatment of Radioiodine-Refractory Differentiated Thyroid Cancer: Combining Immune Checkpoint Inhibitors with VEGF Inhibitors
Young Joo Park
Clinical Thyroidology®.2024; 36(10): 377. CrossRef

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

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

Citations

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Radioactive Iodine in Differentiated Thyroid Cancer: Effect on Detection of Distant Metastases Comparing 4 Guidelines
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Thyroid nodules: diagnosis and management
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Thyroid cancer-specific mortality during 2005–2018 in Korea, aftermath of the overdiagnosis issue: a nationwide population-based cohort study
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Endocrinology and Metabolism.2023; 38(1): 72. CrossRef
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Endocrinology and Metabolism.2023; 38(1): 75. CrossRef
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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
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ARTS is essential for di-2-ethylhexyl phthalate (DEHP)-induced apoptosis of mouse Leydig cells
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Review Articles

Thyroid
Mechanisms of TERT Reactivation and Its Interaction with BRAF^V600E: Young Shin Song, Young Joo Park; Endocrinol Metab. 2020;35(3):515-525. Published online September 22, 2020; DOI: https://doi.org/10.3803/EnM.2020.304

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The telomerase reverse transcriptase (TERT) gene, which is repressed in most differentiated human cells, can be reactivated by somatic TERT alterations and epigenetic modulations. Moreover, the recruitment, accessibility, and binding of transcription factors also affect the regulation of TERT expression. Reactivated TERT contributes to the development and progression of cancer through telomere lengthening-dependent and independent ways. In particular, because of recent advances in high-throughput sequencing technologies, studies on genomic alterations in various cancers that cause increased TERT transcriptional activity have been actively conducted. TERT reactivation has been reported to be associated with poor prognosis in several cancers, and TERT promoter mutations are among the most potent prognostic markers in thyroid cancer. In particular, when a TERT promoter mutation coexists with the BRAF^V600E mutation, these mutations exert synergistic effects on a poor prognosis. Efforts have been made to uncover the mechanisms of these synergistic interactions. In this review, we discuss the role of TERT reactivation in tumorigenesis, the mechanisms of TERT reactivation across all human cancers and in thyroid cancer, and the mechanisms of interactions between BRAF^V600E and TERT promoter mutations.

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Thyroid
Recent Improvements in Genomic and Transcriptomic Understanding of Anaplastic and Poorly Differentiated Thyroid Cancers: Seong-Keun Yoo, Young Shin Song, Young Joo Park, Jeong-Sun Seo; Endocrinol Metab. 2020;35(1):44-54. Published online March 19, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.1.44

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Anaplastic thyroid cancer (ATC) is a lethal human cancer with a 5-year survival rate of less than 10%. Recently, its genomic and transcriptomic characteristics have been extensively elucidated over 5 years owing to advance in high throughput sequencing. These efforts have extended molecular understandings into the progression mechanisms and therapeutic vulnerabilities of aggressive thyroid cancers. In this review, we provide an overview of genomic and transcriptomic alterations in ATC and poorly-differentiated thyroid cancer, which are distinguished from differentiated thyroid cancers. Clinically relevant genomic alterations and deregulated signaling pathways will be able to shed light on more effective prevention and stratified therapeutic interventions for affected patients.

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Namgok Lecture 2018

Thyroid
Genomic Characterization of Differentiated Thyroid Carcinoma: Young Shin Song, Young Joo Park; Endocrinol Metab. 2019;34(1):1-10. Published online March 21, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.1.1

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Since the release of The Cancer Genome Atlas study of papillary thyroid carcinoma (PTC) in 2014, additional genomic studies of differentiated thyroid carcinoma (DTC) using massively-parallel sequencing (MPS) have been published. Recent advances in MPS technology have started to provide important insights into the molecular pathogenesis of DTC. In the genomic landscape, the most recurrently altered genes in DTC, which has a low mutational burden relative to other cancers, are BRAF, RAS, and fusion genes. Some novel driver candidates also have been identified. The frequency of these genomic alterations varies across the subtypes of DTC (classical PTC, follicular variant of PTC, and follicular thyroid carcinoma). Telomerase reverse transcriptase (TERT) promoter mutations are the alteration that makes the most important contribution to the progression of DTC. In the transcriptomic landscape, DTC can be classified according to its gene expression profile, and each subtype has a distinct mutational profile, intracellular signaling output, and clinicopathological characteristics. Herein, we review the results of genomic studies using MPS technology, and describe the types and frequencies of genomic alterations according to histological classifications of DTC and the characteristics and significance of the gene expression signatures of DTC.

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Original Article

Clinical Study
Effects of Maternal Iodine Status during Pregnancy and Lactation on Maternal Thyroid Function and Offspring Growth and Development: A Prospective Study Protocol for the Ideal Breast Milk Cohort: Young Ah Lee, Sun Wook Cho, Ho Kyung Sung, Kyungsik Kim, Young Shin Song, Sin Je Moon, Jung Won Oh, Dal Lae Ju, Sooyeon Choi, Sang Hoon Song, Gi Jeong Cheon, Young Joo Park, Choong Ho Shin, Sue K. Park, Jong Kwan Jun, June-Key Chung; Endocrinol Metab. 2018;33(3):395-402. Published online September 18, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.3.395

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Background

Iodine is an intrinsic element of thyroid hormone, which is essential for childhood growth and development. The Ideal Breast Milk (IBM) cohort study aims to evaluate the effects of maternal iodine status during pregnancy and lactation on maternal thyroid function, offspring growth and development, and offspring thyroid function.

Methods

The IBM cohort study recruited pregnant women from Seoul National University Hospital between June 2016 and August 2017, followed by enrollment of their offspring after delivery. For the maternal participants, iodine status is evaluated by urinary iodine concentration (UIC) and dietary records in the third trimester and at 3 to 4 weeks and 12 to 15 months postpartum. For the child participants, cord blood sampling and UIC measurements are performed at birth. At 3 to 4 weeks of age, UIC and breastmilk iodine concentrations are measured. At 12 to 15 months of age, growth and development are assessed and measurements of UIC, a thyroid function test, and ultrasonography are performed.

Results

A total of 198 pregnant women in their third trimester were recruited. Their mean age was 35.1±3.5 years, and 78 (39.4%) of them were pregnant with twins. Thirty-three (16.7%) of them had a previous history of thyroid disease.

Conclusion

Korea is an iodine-replete area. In particular, lactating women in Korea are commonly exposed to excess iodine due to the traditional practice of consuming brown seaweed soup postpartum. The study of the IBM cohort is expected to contribute to developing guidelines for optimal iodine nutrition in pregnant or lactating women.

Citations

Citations to this article as recorded by

Exposure to and Transplacental Transfer of Per- and Polyfluoroalkyl Substances in a Twin Pregnancy Cohort in Korea
Na-Youn Park, Sun Wook Cho, Ye Eun Seo, Heeyeon Chae, Inae Lee, Young Ah Lee, Jong Kwan Jun, Eun Na Kim, Jeong-Won Oh, Kyungho Choi, Younglim Kho
Environmental Science & Technology.2024; 58(48): 21120. CrossRef
High intakes of iodine among women during pregnancy and the postpartum period has no adverse effect on thyroid function
Dal Lae Ju, Sun Wook Cho, Chae Won Chung, Young Ah Lee, Gi Jeong Cheon, Young Joo Park, Choong Ho Shin, Jong Kwan Jun, June-Key Chung, Sue K. Park, YoonJu Song
European Journal of Nutrition.2023; 62(1): 239. CrossRef
Associations between maternal thyroid function in pregnancy and child neurodevelopmental outcomes at 20 months in the Seychelles Child Development Study, Nutrition Cohort 2 (SCDS NC2)
Anna M. Monaghan, Maria S. Mulhern, Emeir M. Mc Sorley, J.J. Strain, Theresa Winter, Edwin van Wijngaarden, Gary J. Myers, Philip W. Davidson, Conrad Shamlaye, Jude Gedeon, Alison J. Yeates
Journal of Nutritional Science.2021;[Epub] CrossRef

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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Invasiveness and Metastatic Aggressiveness in Small Differentiated Thyroid Cancers: Demography of Small Papillary Thyroid Carcinomas in the Swedish Population
Haytham Bayadsi, Martin Bergman, Malin Sund, Joakim Hennings
World Journal of Surgery.2020; 44(2): 461. CrossRef
Clinical and pathologic predictors of lymph node metastasis in papillary thyroid microcarcinomas
Ling Zhao, Xiaoya Sun, Yukun Luo, Fulin Wang, Zhaohui Lyu
Annals of Diagnostic Pathology.2020; 49: 151647. CrossRef

Original Article

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

Citations to this article as recorded by

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