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Thyroid
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; Endocrinol Metab. 2025;40(4):655-656. Published online July 23, 2025; DOI: https://doi.org/10.3803/EnM.2025.2495

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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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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.

Citations

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Who Really Needs RAI Ablation Therapy for Low-to-Intermediate Risk Differentiated Thyroid Cancer? Insights from the IoN Trial
Young Joo Park
Clinical Thyroidology®.2025; 37(9): 323. CrossRef
From Classification to Personalization: Advances in Thyroid Cancer Risk Stratification Systems
Mijin Kim, Bo Hyun Kim
Endocrinology and Metabolism.2025; 40(5): 689. CrossRef
Thyroglobulin Cutoffs after Total Thyroidectomy Without Radioiodine in Low- to Intermediate-Risk Thyroid Cancer: A Multicenter Cohort Study
Mijin Kim, Eun Kyung Lee, Kyeong Jin Kim, Soo Myoung Shin, Jinsun Jang, Je Yoon Shin, Meihua Jin, Ja Seong Bae, Kwangsoon Kim, Won Gu Kim, Min Ji Jeon, Seung Heon Kang, Hee Kyung Kim, Jee Hee Yoon, Yea Eun Kang, Hwa Young Ahn, Young Joo Park, Bo Hyun Kim
Thyroid®.2025;[Epub] CrossRef
Diagnostic Challenges, Prognostic Assessment, and Treatment Strategies in High-Grade Differentiated Thyroid Carcinoma
Chan Kwon Jung, Agnes Stephanie Harahap
Endocrinology and Metabolism.2025; 40(6): 830. CrossRef

Thyroid
2025 Korean Thyroid Association Management Guidelines for Radioactive Iodine Therapy in Patients with Hyperthyroidism: Kyeong Jin Kim, Eyun Song, Mijin Kim, Hyemi Kwon, Eu Jeong Ku, Hyun Woo Kwon, Jee Hee Yoon, Eun Kyung Lee, Won Woo Lee, Young Joo Park, Dong-Jun Lim, Sun Wook Kim, Ho-Cheol Kang, Jae Hoon Chung, Tae Yong Kim, Sin Gon Kim, Dong Gyu Na, Jee Soo Kim; Endocrinol Metab. 2025;40(3):342-356. Published online June 24, 2025; DOI: https://doi.org/10.3803/EnM.2025.2464

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Abstract PDF PubReader ePub: Hyperthyroidism is a condition marked by excessive thyroid hormone production, most commonly due to Graves’ disease. Treatment options include antithyroid drugs (ATD), radioactive iodine (RAI) therapy, and thyroidectomy. To develop standardized clinical recommendations for RAI therapy with a focus on safety, efficacy, and monitoring, the Korean Thyroid Association formed a task force to create evidence-based guidelines. Six key clinical questions were identified through expert consensus, and a systematic literature review from 2013 to 2022 was conducted. Clinical indications for RAI therapy were categorized into three groups: strongly recommended, may be considered, and not recommended. A fixed dose of 10 to 15 mCi is recommended. Although a strict low-iodine diet is unnecessary, iodine-rich foods should be avoided for at least 1 week before treatment. ATD should be stopped 3 to 7 days before RAI and may be resumed in select cases. Prophylactic glucocorticoids are recommended for patients with mildly active thyroid eye disease and may be considered for others at risk. Thyroid function should be monitored at 4–6 weeks post-treatment, every 2–3 months until stabilized, and then every 6–12 months. These guidelines highlight recent advances and underscore the importance of individualized treatment based on clinical features, comorbidities, and patient preferences in Korea.

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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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.

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Feasibility and Safety of Active Surveillance in Subcapsular Thyroid Nodules with High Suspicion for Malignancy
Yan Hu, Wei Zhou, Lu Zhang, Weiwei Zhan
Ultrasound in Medicine & Biology.2026;[Epub] CrossRef
Optimal cutoff value of fine-needle aspiration thyroglobulin of metastatic lymph node in thyroid cancer patients
Yang Yang, Xianfeng Jiang
European Journal of Surgical Oncology.2025; 51(11): 110428. CrossRef
Low-risk thyroid cancer: surgery or active surveillance—an application of shared decision-making: a narrative review
Min Joo Kim, Eun Kyung Lee, Sun Wook Cho, Yoo Hyung Kim, Kyu Eun Lee, Su-jin Kim, Woochul Kim, Eun-Jae Chung, Jungirl Seok, Yul Hwangbo, Young Ki Lee, Jinsun Jang, Junsun Ryu, Yuh-Seog Jung, Chang Hwan Ryu, Jae Hoon Moon, June Young Choi, Hyeong Won Yu, K
Journal of the Korean Medical Association.2025; 68(9): 573. CrossRef

Original Articles

Thyroid
Comparison of Ultrasensitive and Highly Sensitive Assay to Predict Stimulated Thyroglobulin Levels Using Unstimulated Levels in Differentiated Thyroid Cancer Patients: Jinsun Jang, Hyun Joo Kim, Seunggyun Ha, Kyong Yeun Jung, Gyeongseo Jung, Sun Wook Cho, Do Joon Park, Gi Jeong Cheon, Young Joo Park; Endocrinol Metab. 2025;40(5):759-771. Published online June 5, 2025; DOI: https://doi.org/10.3803/EnM.2025.2302

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Background
Thyroglobulin (Tg) measurement is an essential aspect of monitoring for differentiated thyroid cancer (DTC) patients. This study compared the performances of ultrasensitive Tg (ultraTg) and highly sensitive Tg (hsTg) assays in predicting stimulated Tg levels without thyroid-stimulating hormone stimulation.
Methods
Overall, 268 DTC patients who had undergone total thyroidectomy and either radioiodine treatment or I-123 diagnostic scanning were included. Unstimulated and stimulated Tg levels were measured using hsTg (BRAHMS Dynotest Tg-plus) and ultraTg (RIAKEY Tg immunoradiometric assay) assays. Correlations of each assay with the ability of unstimulated Tg levels to predict stimulated Tg ≥1 ng/mL were analyzed.
Results
hsTg and ultraTg showed a strong correlation (R=0.79, P<0.01); the correlation was weaker in Tg antibody-positive patients (R=0.52). UltraTg demonstrated higher sensitivity in predicting stimulated Tg ≥1 ng/mL compared with hsTg. The optimal cut-off for ultraTg was 0.12 ng/mL (sensitivity, 72.0%; specificity, 67.2%). hsTg at 0.105 ng/mL had lower sensitivity (39.8%) but higher specificity (91.5%). Eight discordant cases with low hsTg (<0.2 ng/mL) but elevated ultraTg (>0.23 ng/mL) were identified; three developed structural recurrence within 3.4 to 5.8 years. Two patients had an excellent response according to hsTg but an indeterminate or biochemical incomplete response according to ultraTg.
Conclusion
UltraTg demonstrated higher sensitivity in predicting positive stimulated Tg levels and potential recurrence compared with hsTg. However, its lower specificity may lead to more frequent classifications of biochemical incomplete response. UltraTg may be beneficial in clinically suspicious cases where hsTg falls below the cut-off, but its broader applicability requires further investigation.

Citations

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Unstimulated Highly Sensitive Thyroglobulin <0.2 ng/mL: Insufficient to Predict Stimulated Thyroglobulin <1 ng/mL?
Tae Yong Kim
Endocrinology and Metabolism.2025; 40(5): 687. CrossRef
Post-thyroidectomy ultrasonography versus thyroglobulin as a surveillance tool for locoregional recurrence in patients with differentiated thyroid carcinoma: A single centre 10-year study
Abhishek Mahajan, Vineeth Kurki, Pranjal Rai, Nilesh Sable, Ujjwal Agarwal, Richa Vaish, Nivedita Chakrabarty, Shreya Shukla, Anil D’Cruz, Prathamesh Pai, Kumar Prabhash, Vanita Noronha, Vijay Patil, Nandini Menon, Sarbani Ghosh Laskar, Asawari Patil, Mun
Frontiers in Endocrinology.2025;[Epub] CrossRef

Thyroid
Study Protocol of Expanded Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro-EXP): Jae Hoon Moon, Eun Kyung Lee, Wonjae Cha, Young Jun Chai, Sun Wook Cho, June Young Choi, Sung Yong Choi, A Jung Chu, Eun-Jae Chung, Yul Hwangbo, Woo-Jin Jeong, Yuh-Seog Jung, Kyungsik Kim, Min Joo Kim, Su-jin Kim, Woochul Kim, Yoo Hyung Kim, Chang Yoon Lee, Ji Ye Lee, Kyu Eun Lee, Young Ki Lee, Hunjong Lim, Do Joon Park, Sue K. Park, Chang Hwan Ryu, Junsun Ryu, Jungirl Seok, Young Shin Song, Ka Hee Yi, Hyeong Won Yu, Eleanor White, Katerina Mastrocostas, Roderick J. Clifton-Bligh, Anthony Glover, Matti L. Gild, Ji-hoon Kim, Young Joo Park; Endocrinol Metab. 2025;40(2):236-246. Published online February 18, 2025; DOI: https://doi.org/10.3803/EnM.2024.2136

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Background
Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making.
Methods
This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes.
Conclusion
This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.

Citations

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

Thyroid
Distinct Impacts of Clinicopathological and Mutational Profiles on Long-Term Survival and Recurrence in Medullary Thyroid Carcinoma: Moon Young Oh, Kyong Yeun Jung, Hoonsung Choi, Young Jun Chai, Sun Wook Cho, Su-jin Kim, Kyu Eun Lee, Eun-Jae Chung, Do Joon Park, Young Joo Park, Han-Kwang Yang; Endocrinol Metab. 2024;39(6):877-890. Published online November 5, 2024; DOI: https://doi.org/10.3803/EnM.2024.2027

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Background
Medullary thyroid carcinoma (MTC) has a poorer prognosis than differentiated thyroid cancers; however, comprehensive data on the long-term outcomes of MTC remain scarce. This study investigated the extended clinical outcomes of MTC and aimed to identify prognostic factors.
Methods
Patients diagnosed with MTC between 1980 and 2020 were retrospectively reviewed. Their clinical characteristics, longterm clinical outcomes, and prognostic factors for recurrence and mortality were analyzed.
Results
The study included 226 patients (144 women, 82 men). The disease-specific survival (DSS) rates for all MTC patients at 5-, 10-, 20-, and 30-year intervals were 92.7%, 89.4%, 74.3%, and 68.1%, respectively. The recurrence-free survival (RFS) rates were 71.1%, 56.1%, 40.2%, and 32.1% at these intervals. DSS was comparable between the groups from 1980–2009 and 2010–2020 (P=0.995); however, the 1980–2009 group had significantly lower RFS rates (P=0.031). The 2010–2020 group exhibited greater extents of surgical and lymph node dissection (P=0.003) and smaller tumors (P=0.003). Multivariate analysis identified extrathyroidal extension as the strongest prognostic factor for both RFS and DSS. Age >55 years and tumor size of ≥2 cm were also significant prognostic factors for DSS, while hereditary disease and lymph node metastasis were significant for RFS. Survival analysis after propensity-score matching of rearranged during transfection (RET)-negative and non-screened RET-positive groups showed comparable DSS but longer RFS in the RET-negative group.
Conclusion
Extrathyroidal extension was identified as the strongest prognostic factor for RFS and DSS. Older age and larger tumor size were associated with decreased DSS, while RET mutation and lymph node metastasis significantly impacted RFS.

Citations

Citations to this article as recorded by

The impact of microscopic extrathyroidal extension on the prognosis of medullary thyroid carcinoma: A multicenter cohort study
Beyza Olcay Ozturk, Umran Keskin, Serhat Uysal, Aysa Hacioglu, Seda Karsli, Burak Andac, Umit Nur Ozbay, Hulyanur Sodan, Sebnem Burhan, Coskun Ates, Ugur Avci, Faruk Kilinc, Selvinaz Erol, Merve Catak, Zafer Pekkolay, Gulhan Akbaba, Goknur Yorulmaz, Sakin
Endocrinología, Diabetes y Nutrición.2025; 72(10): 501633. CrossRef
The impact of microscopic extrathyroidal extension on the prognosis of medullary thyroid carcinoma: A multicenter cohort study
Beyza Olcay Ozturk, Umran Keskin, Serhat Uysal, Aysa Hacioglu, Seda Karsli, Burak Andac, Umit Nur Ozbay, Hulyanur Sodan, Sebnem Burhan, Coskun Ates, Ugur Avci, Faruk Kilinc, Selvinaz Erol, Merve Catak, Zafer Pekkolay, Gulhan Akbaba, Goknur Yorulmaz, Sakin
Endocrinología, Diabetes y Nutrición (English ed.).2025; 72(10): 501633. CrossRef

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

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.

Review Articles

Thyroid
Active Surveillance for Low-Risk Thyroid Cancers: A Review of Current Practice Guidelines: Min Joo Kim, Jae Hoon Moon, Eun Kyung Lee, Young Shin Song, Kyong Yeun Jung, Ji Ye Lee, Ji-hoon Kim, Kyungsik Kim, Sue K. Park, Young Joo Park; Endocrinol Metab. 2024;39(1):47-60. Published online February 15, 2024; DOI: https://doi.org/10.3803/EnM.2024.1937

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The indolent nature and favorable outcomes associated with papillary thyroid microcarcinoma have prompted numerous prospective studies on active surveillance (AS) and its adoption as an alternative to immediate surgery in managing low-risk thyroid cancer. This article reviews the current status of AS, as outlined in various international practice guidelines. AS is typically recommended for tumors that measure 1 cm or less in diameter and do not exhibit aggressive subtypes on cytology, extrathyroidal extension, lymph node metastasis, or distant metastasis. To determine the most appropriate candidates for AS, factors such as tumor size, location, multiplicity, and ultrasound findings are considered, along with patient characteristics like medical condition, age, and family history. Moreover, shared decision-making, which includes patient-reported outcomes such as quality of life and cost-effectiveness, is essential. During AS, patients undergo regular ultrasound examinations to monitor for signs of disease progression, including tumor growth, extrathyroidal extension, or lymph node metastasis. In conclusion, while AS is a feasible and reliable approach for managing lowrisk thyroid cancer, it requires careful patient selection, effective communication for shared decision-making, standardized follow-up protocols, and a clear definition of disease progression.

Citations

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Active Surveillance for Locoregional Recurrent Differentiated Thyroid Cancer: A Systematic Review and Meta-Analysis
Hunjong Lim, Se Jin Cho, Jung Hwan Baek
Thyroid®.2026;[Epub] CrossRef
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
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.2025; 16(3): 743. 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
Journal of Personalized Medicine.2025; 15(3): 84. CrossRef
Exploration of immunocytochemical biomarkers related to central lymph node metastasis in papillary thyroid microcarcinoma
Lulu Rong, Jie Wang, Qian Wang, Yanli Zhu, Wenhao Ren
Cytojournal.2025; 22: 18. CrossRef
Study Protocol of Expanded Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro-EXP)
Jae Hoon Moon, Eun Kyung Lee, Wonjae Cha, Young Jun Chai, Sun Wook Cho, June Young Choi, Sung Yong Choi, A Jung Chu, Eun-Jae Chung, Yul Hwangbo, Woo-Jin Jeong, Yuh-Seog Jung, Kyungsik Kim, Min Joo Kim, Su-jin Kim, Woochul Kim, Yoo Hyung Kim, Chang Yoon Le
Endocrinology and Metabolism.2025; 40(2): 236. CrossRef
2024 International Expert Consensus on US-guided Thermal Ablation for T1N0M0 Papillary Thyroid Cancer
Zhen-long Zhao, Shu-rong Wang, Jennifer Kuo, Bülent Çekiç, Lei Liang, Hossam Arafa Ghazi, Shu-hang Xu, Gerardo Amabile, Song-song Wu, Ajit Yadav, Gang Dong, Ingo Janssen, Bo-qiang Fan, Nobuhiro Fukunari, Jun-feng He, Le Thanh Dung, Song-yuan Yu, Sum Leong
Radiology.2025;[Epub] CrossRef
Ultrasound and gene-guided microwave ablation vs. surgery for low-risk papillary thyroid carcinoma: a prospective observational cohort study
Yunfang Yu, Yuxin Shen, Yujie Tan, Yisikandaer Yalikun, Tian Tian, Qingqing Tang, Qiyun Ou, Yue Zhu, Miaoyun Long
Precision Clinical Medicine.2025;[Epub] CrossRef
Global research landscape on active surveillance for papillary thyroid microcarcinoma: a bibliometric analysis
Dong-Shu Kang, Yu-Hao Lin, Jian-Qing Tian
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Thyroid
A Narrative Review of the 2023 Korean Thyroid Association Management Guideline for Patients with Thyroid Nodules: Eun Kyung Lee, Young Joo Park, Chan Kwon Jung, Dong Gyu Na; Endocrinol Metab. 2024;39(1):61-72. Published online February 14, 2024; DOI: https://doi.org/10.3803/EnM.2024.1938

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The 2023 Korean Thyroid Association (KTA) Management Guideline for Patients with Thyroid Nodules constitute an update of the 2016 KTA guideline for thyroid nodules and cancers that focuses specifically on nodules. The 2023 guideline aim to offer updated guidance based on new evidence that reflects the changes in clinical practice since the 2016 KTA guideline. To update the 2023 guideline, a comprehensive literature search was conducted from January 2022 to May 2022. The literature search included studies, reviews, and other evidence involving human subjects that were published in English in MEDLINE (PubMed), Embase, and other relevant databases. Additional significant clinical trials and research studies published up to April 2023 were also reviewed. The limitations of the current evidence are discussed, and suggestions for areas in need of further research are identified. The purpose of this review is to provide a summary of the 2023 KTA guideline for the management of thyroid nodules released in May 2023 and to give a balanced insight with comparison of recent guidelines from other societies.

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Original Articles

Thyroid
Hashimoto Thyroiditis and Mortality in Patients with Differentiated Thyroid Cancer: The National Epidemiologic Survey of Thyroid Cancer in Korea and Meta-Analysis: Injung Yang, Jae Myung Yu, Hye Soo Chung, Yoon Jung Kim, Yong Kyun Roh, Min Kyu Choi, Sung-ho Park, Young Joo Park, Shinje Moon; Endocrinol Metab. 2024;39(1):140-151. Published online January 3, 2024; DOI: https://doi.org/10.3803/EnM.2023.1748

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Background
Many studies have shown that Hashimoto’s thyroiditis (HT) acts as a protective factor in differentiated thyroid cancer (DTC), but little is known about its effects on mortality. Therefore, this study was performed to reveal the prognosis of HT on mortality in patients with DTC.
Methods
This study included two types of research results: retrospective cohort study using the National Epidemiologic Survey of Thyroid cancer (NEST) in Korea and meta-analysis study with the NEST data and eight selected studies.
Results
Of the 4,398 patients with DTC in NEST, 341 patients (7.8%) died during the median follow-up period of 15 years (interquartile range, 12.3 to 15.6). Of these, 91 deaths (2.1%) were related to DTC. HT was associated with a smaller tumor size and less aggressive DTC. In Cox regression analysis after adjusting for age and sex, patients with HT showed a significantly lower risk of all-cause death (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.52 to 0.96) and DTC-related death (HR, 0.33; 95% CI, 0.14 to 0.77). The analysis with inverse probability of treatment weight data adjusted for age, sex, and year of thyroid cancer registration showed similar association. The meta-analysis showed that patients with HT showed a lower risk of all-cause mortality (risk ratio [RR], 0.24; 95% CI, 0.13 to 0.47) and thyroid cancer-related mortality (RR, 0.23; 95% CI, 0.13 to 0.40) in comparison with patients without HT.
Conclusion
This study showed that DTC co-presenting with HT is associated with a low risk of advanced DTC and presents a low risk for all-cause and DTC-related death.

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Risk Stratification for Thyroid Malignancies in Chronic Lymphocytic Thyroiditis
Anna Krzentowska, Aleksander Konturek, Filip Gołkowski, Anna Merklinger-Gruchała, Marcin Barczyński
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Global Thyroid Cancer Patterns and Predictive Analytics: Integrating Machine Learning for Advanced Diagnostic Modelling
Yao Sun, Yongsheng Jia, Kuan Fu, Xiaoyong Yang, Peiguo Wang, Zhiyong Yuan
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KangJiaFang granules ameliorates experimental autoimmune thyroiditis by regulating CD4+ T cells and altering gut microbiota
Yuemeng Fu, Yanyan Zheng, Chuntao Xie, Jingjing Guo, Binheng Liu, Cheng Qian, Yuan Wang
Fitoterapia.2025; 187: 106936. CrossRef
Germline polymorphisms of the NOD2 pathway may predict the effectiveness of radioiodine in differentiated thyroid cancer treatment
M. Borowczyk, M. Kaczmarek-Ryś, S. Hryhorowicz, M. Sypniewski, D. Filipowicz, P. Dobosz, M. Oszywa, M. Ruchała, K. Ziemnicka
Journal of Endocrinological Investigation.2024; 47(12): 2969. CrossRef

Thyroid Big Data Articles (National Health Insurance Service Database)
Prevalence, Treatment Status, and Comorbidities of Hyperthyroidism in Korea from 2003 to 2018: A Nationwide Population Study: Hwa Young Ahn, Sun Wook Cho, Mi Young Lee, Young Joo Park, Bon Seok Koo, Hang-Seok Chang, Ka Hee Yi; Endocrinol Metab. 2023;38(4):436-444. Published online July 12, 2023; DOI: https://doi.org/10.3803/EnM.2023.1684

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Background
This study aimed to investigate the changes of incidence and treatment of choice for hyperthyroidism from 2003 to 2018 and explore the treatment-related complications and concomitant comorbidities in South Korea using data from the National Health Insurance Service.
Methods
This is a retrospective observational study. Hyperthyroidism was defined as a case having two or more diagnostic codes of thyrotoxicosis, with antithyroid drug intake for more than 6 months.
Results
The average age-standardized incidence of hyperthyroidism from 2003 to 2018 was 42.23 and 105.13 per 100,000 men and women, respectively. In 2003 to 2004, hyperthyroidism was most often diagnosed in patients in their 50s, but in 2017 to 2018, people were most often diagnosed in their 60s. During the entire period, about 93.7% of hyperthyroidism patients were prescribed with antithyroid drugs, and meanwhile, the annual rates of ablation therapy decrease from 7.68% in 2008 to 4.56% in 2018. Antithyroid drug-related adverse events, mainly agranulocytosis and acute hepatitis, as well as complications of hyperthyroidism such as atrial fibrillation or flutter, osteoporosis, and fractures, occurred more often in younger patients.
Conclusion
In Korea, hyperthyroidism occurred about 2.5 times more in women than in men, and antithyroid drugs were most preferred as the first-line treatment. Compared to the general population, hyperthyroid patients may have a higher risk of atrial fibrillation or flutter, osteoporosis, and fractures at a younger age.

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Effect of COVID-19 Vaccination on Thyroid Disease in 7 Million Adult and 0.2 Million Adolescent Vaccine Recipients
Sungho Bea, Hwa Young Ahn, Jieun Woo, Ju-Young Shin, Sun Wook Cho
The Journal of Clinical Endocrinology & Metabolism.2025; 110(9): e3109. CrossRef
Unveiling Risk Factors for Treatment Failure in Patients with Graves’ Disease: A Nationwide Cohort Study in Korea
Jung A Kim, Kyeong Jin Kim, Jimi Choi, Kyoung Jin Kim, Eyun Song, Ji Hee Yu, Nam Hoon Kim, Hye Jin Yoo, Ji A Seo, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Sin Gon Kim
Endocrinology and Metabolism.2025; 40(1): 125. CrossRef
2025 Korean Thyroid Association Management Guidelines for Radioactive Iodine Therapy in Patients with Hyperthyroidism
Kyeong Jin Kim, Eyun Song, Mijin Kim, Hyemi Kwon, Eu Jeong Ku, Hyun Woo Kwon, Jee Hee Yoon, Eun Kyung Lee, Won Woo Lee, Young Joo Park, Dong-Jun Lim, Sun Wook Kim, Ho-Cheol Kang, Jae Hoon Chung, Tae Yong Kim, Sin Gon Kim, Dong Gyu Na, Jee Soo Kim
International Journal of Thyroidology.2025; 18(1): 65. CrossRef
2025 Korean Thyroid Association Management Guidelines for Radioactive Iodine Therapy in Patients with Hyperthyroidism
Kyeong Jin Kim, Eyun Song, Mijin Kim, Hyemi Kwon, Eu Jeong Ku, Hyun Woo Kwon, Jee Hee Yoon, Eun Kyung Lee, Won Woo Lee, Young Joo Park, Dong-Jun Lim, Sun Wook Kim, Ho-Cheol Kang, Jae Hoon Chung, Tae Yong Kim, Sin Gon Kim, Dong Gyu Na, Jee Soo Kim
Endocrinology and Metabolism.2025; 40(3): 342. CrossRef
A Digital Software Support Platform for Hyperthyroidism Management in South Korea: Markov Simulation Model-Based Cost-Effectiveness Analysis
Jung Hyun Kim, Jaeyong Shin, Man S Kim, Jae Hoon Moon
JMIR mHealth and uHealth.2025; 13: e56738. CrossRef
Long-term Effect of Thyrotropin-binding Inhibitor Immunoglobulin on Atrial Fibrillation in Euthyroid Patients
Jung-Chi Hsu, Kang-Chih Fan, Ting-Chuan Wang, Shu-Lin Chuang, Ying-Ting Chao, Ting-Tse Lin, Kuan-Chih Huang, Lian-Yu Lin, Lung-Chun Lin
Endocrine Practice.2024; 30(6): 537. CrossRef
Treatment Patterns and Preferences for Graves’ Disease in Korea: Insights from a Nationwide Cohort Study
Kyeong Jin Kim, Jimi Choi, Soo Myoung Shin, Jung A Kim, Kyoung Jin Kim, Sin Gon Kim
Endocrinology and Metabolism.2024; 39(4): 659. CrossRef
Dynamic Risk Model for the Medical Treatment of Graves’ Hyperthyroidism according to Treatment Duration
Meihua Jin, Chae A Kim, Min Ji Jeon, Won Bae Kim, Tae Yong Kim, Won Gu Kim
Endocrinology and Metabolism.2024; 39(4): 579. CrossRef
The Current Status of Hyperthyroidism in Korea
Hyemi Kwon
Endocrinology and Metabolism.2023; 38(4): 392. CrossRef
Is Thyroid Dysfunction Associated with Unruptured Intracranial Aneurysms? A Population-Based, Nested Case–Control Study from Korea
Hyeree Park, Sun Wook Cho, Sung Ho Lee, Kangmin Kim, Hyun-Seung Kang, Jeong Eun Kim, Aesun Shin, Won-Sang Cho
Thyroid®.2023; 33(12): 1483. CrossRef

Thyroid Thyroid Cancer Screening
Survival Comparison of Incidentally Found versus Clinically Detected Thyroid Cancers: An Analysis of a Nationwide Cohort Study: Shinje Moon, Eun Kyung Lee, Hoonsung Choi, Sue K. Park, Young Joo Park; Endocrinol Metab. 2023;38(1):81-92. Published online February 27, 2023; DOI: https://doi.org/10.3803/EnM.2023.1668

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Background
The true benefit of thyroid cancer screening is incompletely understood. This study investigated the impact of ultrasound screening on thyroid cancer outcomes through a comparison with symptomatic thyroid cancer using data from a nationwide cohort study in Korea.
Methods
Cox regression analysis was performed to assess the hazard ratios (HRs) for all-cause and thyroid cancer-specific mortality. Considering the possible bias arising from age, sex, year of thyroid cancer registration, and confounding factors for mortality (including smoking/drinking status, diabetes, and hypertension), all analyses were conducted with stabilized inverse probability of treatment weighting (IPTW) according to the route of detection.
Results
Of 5,796 patients with thyroid cancer, 4,145 were included and 1,651 were excluded due to insufficient data. In comparison with the screening group, the clinical suspicion group was associated with large tumors (17.2±14.6 mm vs. 10.4±7.9 mm), advanced T stage (3–4) (odds ratio [OR], 1.24; 95% confidence interval [CI], 1.09 to 1.41), extrathyroidal extension (OR, 1.16; 95% CI, 1.02 to 1.32), and advanced stage (III–IV) (OR, 1.16; 95% CI, 1.00 to 1.35). In IPTW-adjusted Cox regression analysis, the clinical suspicion group had significantly higher risks of all-cause mortality (HR, 1.43; 95% CI, 1.14 to 1.80) and thyroid cancer-specific mortality (HR, 3.07; 95% CI, 1.77 to 5.29). Mediation analysis showed that the presence of thyroid-specific symptoms was directly associated with a higher risk of cancer-specific mortality. Thyroid-specific symptoms also indirectly affected thyroid cancer-specific mortality, mediated by tumor size and advanced clinicopathologic status.
Conclusion
Our findings provide important evidence for the survival benefit of early detection of thyroid cancer compared to symptomatic thyroid cancer.

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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
Endocrinology and Metabolism.2025; 40(3): 414. CrossRef
Thyroid cancer in Asia: incidence, mortality in 2022, and future projections to 2050
Mengxia Fu, Zhiming Peng, Min Wu
European Journal of Cancer Prevention.2025;[Epub] CrossRef
A One-Year Cross-Sectional Study on the Impact of the Thyroid Imaging Reporting and Data System (TIRADS) on Fine-Needle Aspiration Cytology (FNAC) Decision-Making in a Secondary Care Hospital
Srinivasa Swamy Bandaru, Qahtan A Al Dulaimi
Cureus.2025;[Epub] CrossRef
Cost-Utility Analysis of Early Detection with Ultrasonography of Differentiated Thyroid Cancer: A Retrospective Study on a Korean Population
Han-Sang Baek, Jeonghoon Ha, Kwangsoon Kim, Ja Seong Bae, Jeong Soo Kim, Sungju Kim, Dong-Jun Lim, Chul-Min Kim
Endocrinology and Metabolism.2024; 39(2): 310. CrossRef
Thyroid cancer-specific mortality during 2005–2018 in Korea, aftermath of the overdiagnosis issue: a nationwide population-based cohort study
Kyeong Jin Kim, Jimi Choi, Sue K. Park, Young Joo Park, Sin Gon Kim
International Journal of Surgery.2024; 110(9): 5489. CrossRef
Distinct Impacts of Clinicopathological and Mutational Profiles on Long-Term Survival and Recurrence in Medullary Thyroid Carcinoma
Moon Young Oh, Kyong Yeun Jung, Hoonsung Choi, Young Jun Chai, Sun Wook Cho, Su-jin Kim, Kyu Eun Lee, Eun-Jae Chung, Do Joon Park, Young Joo Park, Han-Kwang Yang
Endocrinology and Metabolism.2024; 39(6): 877. CrossRef
Clinical Characteristics, Diagnostic Approach and Outcome of Thyroid Incidental Findings vs. Clinically Overt Thyroid Nodules: An Observational Single-Centre Study
Tom Jansen, Nike Stikkelbroeck, Annenienke van de Ven, Ilse van Engen-van Grunsven, Marcel Janssen, Han Bonenkamp, Martin Gotthardt, Romana T. Netea-Maier
Cancers.2023; 15(8): 2350. CrossRef
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
Endocrinology and Metabolism.2023; 38(1): 93. CrossRef
To Screen or Not to Screen?
Do Joon Park
Endocrinology and Metabolism.2023; 38(1): 69. CrossRef
The 2017 United States Preventive Services Task Force Recommendation for Thyroid Cancer Screening Is No Longer the Gold Standard
Ka Hee Yi
Endocrinology and Metabolism.2023; 38(1): 72. CrossRef
Thyroid Cancer Screening: How to Maximize Its Benefits and Minimize Its Harms
Jung Hwan Baek
Endocrinology and Metabolism.2023; 38(1): 75. 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.

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International Journal of Surgery.2024; 110(9): 5489. CrossRef
To Screen or Not to Screen?
Do Joon Park
Endocrinology and Metabolism.2023; 38(1): 69. CrossRef
The 2017 United States Preventive Services Task Force Recommendation for Thyroid Cancer Screening Is No Longer the Gold Standard
Ka Hee Yi
Endocrinology and Metabolism.2023; 38(1): 72. CrossRef
Thyroid Cancer Screening: How to Maximize Its Benefits and Minimize Its Harms
Jung Hwan Baek
Endocrinology and Metabolism.2023; 38(1): 75. CrossRef
Delayed Surgery for and Outcomes of Papillary Thyroid Cancer: Is the Pendulum Still Swinging?
Giorgio Grani
Clinical Thyroidology.2023; 35(5): 192. CrossRef

Thyroid
BRAF^V600E Mutation Enhances Estrogen-Induced Metastatic Potential of Thyroid Cancer by Regulating the Expression of Estrogen Receptors: Minjun Kim, Su-jin Kim, Seong Yun Ha, Zhen Xu, Youngjin Han, Hyeon-Gun Jee, Sun Wook Cho, Young Joo Park, Kyu Eun Lee; Endocrinol Metab. 2022;37(6):879-890. Published online December 26, 2022; DOI: https://doi.org/10.3803/EnM.2022.1563

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Background
Cross-talk between mitogen-activated protein kinase and estrogen has been reported; however, the role of BRAF^V600E in the estrogen responsiveness of thyroid cancer is unknown. We elucidated the effect of BRAF^V600E on the estrogen-induced increase in metastatic potential in thyroid cancer.
Methods
Using a pair of cell lines, human thyroid cell lines which harbor wild type BRAF gene (Nthy/WT) and Nthy/BRAF^V600E (Nthy/V600E), the expression of estrogen receptors (ERs) and estrogen-induced metastatic phenotypes were evaluated. Susceptibility to ERα- and ERβ-selective agents was evaluated to confirm differential ER expression. ESR expression was analyzed according to BRAF^V600E status and age (≤50 years vs. >50 years) using The Cancer Genome Atlas (TCGA) data.
Results
Estradiol increased the ERα/ERβ expression ratio in Nthy/V600E, whereas the decreased ERα/ERβ expression ratio was found in Nthy/WT. BRAF^V600E-mutated cell lines showed a higher E2-induced increase in metastatic potential, including migration, invasion, and anchorage-independent growth compared with Nthy/WT. An ERα antagonist significantly inhibited migration in Nthy/V600E cells, whereas an ERβ agonist was more effective in Nthy/WT. In the BRAF^V600E group, ESR1/ESR2 ratio was significantly higher in younger age group (≤50 years) compared with older age group (>50 years) by TCGA data analysis.
Conclusion
Our data show that BRAF^V600E mutation plays a crucial role in the estrogen responsiveness of thyroid cancer by regulating ER expression. Therefore, BRAF^V600E might be used as a biomarker when deciding future hormone therapies based on estrogen signaling in thyroid cancer patients.

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BRAF p.V600E Mutation in Mixed Odontogenic Tumors and Its Clinical Correlation: A Systematic Review and Meta-Analysis
Soranun Chantarangsu, Ekarat Phattarataratip, Aroonwan Lam-ubol
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Three cases of thyroid cancer in transgender female veterans receiving gender-affirming estrogen treatment
John D. Christensen, Hiba T. Basheer
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Thyroid Cancer Prevalence, Risk Exposure, and Clinical Features Among Transgender Female Veterans
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A review of complex hormone regulation in thyroid cancer: novel insights beyond the hypothalamus–pituitary–thyroid axis
Liu-han Chen, Tao Xie, Qian Lei, Yan-rui Gu, Chuan-zheng Sun
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Preoperative Diagnosis of Cervical Lymph Node Metastasis in Papillary Thyroid Carcinoma
瑜瑜叶
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Association of DNA Promoter Methylation and BRAF Mutation in Thyroid Cancer
Farzana Jasmine, Briseis Aschebrook-Kilfoy, Mohammad M. Rahman, Garrett Zaagman, Raymon H. Grogan, Mohammed Kamal, Habibul Ahsan, Muhammad G. Kibriya
Current Oncology.2023; 30(3): 2978. CrossRef
Editorial: Recent advances in papillary thyroid carcinoma: Progression, treatment and survival predictors
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Letter

Thyroid
Re-Increasing Trends in Thyroid Cancer Incidence after a Short Period of Decrease in Korea: Reigniting the Debate on Ultrasound Screening: Chan Kwon Jung, Ja Seong Bae, Young Joo Park; Endocrinol Metab. 2022;37(5):816-818. Published online October 11, 2022; DOI: https://doi.org/10.3803/EnM.2022.1586

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Bilirubin Metabolism and Thyroid Cancer: Insights from ALBI and PALBI Indices
Jong Won Shin, Jae Woong Sull, Nguyen Thien Minh, Sun Ha Jee
Biomolecules.2025; 15(7): 1042. CrossRef
Thyroid cancer in adolescents and young adults: a population-based study in 185 countries worldwide
Mengmeng Li, Luigino Dal Maso, Margherita Pizzato, Harriet Rumgay, Salvatore Vaccarella
The Lancet Diabetes & Endocrinology.2025;[Epub] CrossRef
Bilateral axillo-breast approach robotic total thyroidectomy without isthmectomy: a case report
Hyeji Kim, Hyeonuk Hwang, Hyungju Kwon
The Ewha Medical Journal.2024;[Epub] CrossRef
Contents analysis of thyroid cancer-related information uploaded to YouTube by physicians in Korea: endorsing thyroid cancer screening, potentially leading to overdiagnosis
EunKyo Kang, HyoRim Ju, Soojeong Kim, Juyoung Choi
BMC Public Health.2024;[Epub] CrossRef
Cost-Utility Analysis of Early Detection with Ultrasonography of Differentiated Thyroid Cancer: A Retrospective Study on a Korean Population
Han-Sang Baek, Jeonghoon Ha, Kwangsoon Kim, Ja Seong Bae, Jeong Soo Kim, Sungju Kim, Dong-Jun Lim, Chul-Min Kim
Endocrinology and Metabolism.2024; 39(2): 310. CrossRef
Thyroid Cancer Incidence Among Korean Individuals: A Comparison of South Korea and the United States
Dohun Kim, Guan Li, Peter K. Moon, Yifei Ma, Soohyun Sim, Sung Y. Park, Minkyung Oh, Uchechukwu C. Megwalu
The Laryngoscope.2024; 134(9): 4156. CrossRef
Thyroid cancer-specific mortality during 2005–2018 in Korea, aftermath of the overdiagnosis issue: a nationwide population-based cohort study
Kyeong Jin Kim, Jimi Choi, Sue K. Park, Young Joo Park, Sin Gon Kim
International Journal of Surgery.2024; 110(9): 5489. CrossRef
Changing Trends of Thyroid Cancer Clinical Characteristics and Treatment Pattern in South Korea: Insights from an Institutional Database and the Korean Cancer Center Registry Database
Yung Jee Kang, Nayeon Choi, Jungirl Seok, Sun Wook Kim, Tae-Hyuk Kim, Jae Hoon Chung, Young-Ik Son, Man Ki Chung
International Journal of Thyroidology.2024; 17(2): 277. CrossRef
Survival Comparison of Incidentally Found versus Clinically Detected Thyroid Cancers: An Analysis of a Nationwide Cohort Study
Shinje Moon, Eun Kyung Lee, Hoonsung Choi, Sue K. Park, Young Joo Park
Endocrinology and Metabolism.2023; 38(1): 81. CrossRef
Cumulative exposure to metabolic syndrome increases thyroid cancer risk in young adults: a population-based cohort study
Jinyoung Kim, Kyungdo Han, Mee Kyoung Kim, Ki-Hyun Baek, Ki-Ho Song, Hyuk-Sang Kwon
The Korean Journal of Internal Medicine.2023; 38(4): 526. CrossRef
Cost-Effectiveness of Active Surveillance Compared to Early Surgery of Small Papillary Thyroid Cancer: A Retrospective Study on a Korean Population
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Original Article

Thyroid
Clinical Outcomes of Repeated Radioactive Iodine Therapy for Graves’ Disease: Min Joo Kim, Sun Wook Cho, Ye An Kim, Hoon Sung Choi, Young Joo Park, Do Joon Park, Bo Youn Cho; Endocrinol Metab. 2022;37(3):524-532. Published online June 16, 2022; DOI: https://doi.org/10.3803/EnM.2022.1418

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Background
Radioactive iodine (RAI) therapy is a successful therapeutic modality for Graves’ disease. However, RAI therapy can fail, and RAI therapy after antithyroid drugs (ATDs) has a lower remission rate. Therefore, many patients require repeated RAI therapy. This study investigated the clinical outcomes of repeated RAI therapy for Graves’ disease.
Methods
Patients who underwent RAI therapy as second-line therapy after failure of ATD treatment between 2001 and 2015 were reviewed. Remission was defined as hypothyroid or euthyroid status without ATD, and with or without levothyroxine at 12 months after RAI therapy.
Results
The 1-year remission rate after 2nd RAI therapy (66%, 152/230) is significantly higher than that after 1st RAI therapy (48%, 393/815) or long-term ATD treatment after 1st RAI therapy failure (42%). The clinical response to 2nd RAI therapy was more rapid. The median time intervals from the 2nd RAI therapy to ATD discontinuation (1.3 months) and to the start of levothyroxine replacement (2.5 months) were significantly shorter than those for the 1st RAI therapy. A smaller goiter size, a longer time interval between the 1st and 2nd RAI therapies, and a longer ATD discontinuation period predicted remission after the 2nd RAI therapy. Finally, in 78 patients who failed the 2nd RAI therapy, the mean ATD dosage significantly reduced 5.1 mg over 12 months.
Conclusion
Repeated RAI therapy can be a good therapeutic option, especially in patients with smaller goiters and those who are more responsive to the 1st RAI therapy.

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Outcomes of Fixed-Dose Radioactive Iodine Therapy in Hyperthyroidism and Optimization of Follow-Up After Treatment Failure With Low-Dose Antithyroid Medication
Panita Kantikool, Naphat Buraphanawibun
Cureus.2025;[Epub] CrossRef
Tingkat Keberhasilan Terapi Radioiodin Pertama pada Pasien Graves’ Disease
Aliya Khadijah Kemaleratu, Yuliana Rahmah Retnaningrum, Yudanti Riastiti
Jurnal Sains dan Kesehatan.2025; 6(1): 1. CrossRef
Association of high‐dose radioactive iodine therapy with PPM1D‐mutated clonal hematopoiesis in older individuals
Jaeryuk Kim, Sungwoo Bae, Jaeyong Choi, Sun‐Wha Im, Bukyoung Cha, Gyeongseo Jung, Sun Wook Cho, Eul‐Ju Seo, Young Ah Lee, Jin Chul Paeng, Young Joo Park, Jong‐Il Kim
Molecular Oncology.2025; 19(11): 3079. CrossRef
Characteristics of Japanese patients with Graves’ disease who fail first radioiodine therapy
Yuki Yamamoto, Hiroshi Fukazawa, Jun Ito, Kei Ito, Masanao Fujii, Aiko Hosoda, Yoshinori Osaki, Hiroaki Yagyu
Thyroid Science.2025; 2(4): 100028. CrossRef
Prospective study to evaluate radioactive iodine of 20 mCi vs 10–15 mCi in Graves’ disease
Wasit Kanokwongnuwat, Nawarat Penpong
BMC Endocrine Disorders.2024;[Epub] CrossRef
The Early Changes in Thyroid-Stimulating Immunoglobulin Bioassay over Anti-Thyroid Drug Treatment Could Predict Prognosis of Graves’ Disease
Jin Yu, Han-Sang Baek, Chaiho Jeong, Kwanhoon Jo, Jeongmin Lee, Jeonghoon Ha, Min Hee Kim, Jungmin Lee, Dong-Jun Lim
Endocrinology and Metabolism.2023; 38(3): 338. CrossRef
Effect of liver dysfunction on outcome of radioactive iodine therapy for Graves’ disease
Yuyang Ze, Fei Shao, Xuefeng Feng, Shanmei Shen, Yan Bi, Dalong Zhu, Xiaowen Zhang
BMC Endocrine Disorders.2022;[Epub] CrossRef

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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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

Original Articles

Diabetes, Obesity and Metabolism
The Effects of PPAR Agonists on Atherosclerosis and Nonalcoholic Fatty Liver Disease in ApoE^−/−FXR^−/− Mice: Yenna Lee, Bo-Rahm Kim, Geun-Hyung Kang, Gwan Jae Lee, Young Joo Park, Haeryoung Kim, Hak Chul Jang, Sung Hee Choi; Endocrinol Metab. 2021;36(6):1243-1253. Published online December 28, 2021; DOI: https://doi.org/10.3803/EnM.2021.1100

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Background
Farnesoid X receptor (FXR), a bile acid–activated nuclear receptor, is a potent regulator of glucose and lipid metabolism as well as of bile acid metabolism. Previous studies have demonstrated that FXR deficiency is associated with metabolic derangements, including atherosclerosis and nonalcoholic fatty liver disease (NAFLD), but its mechanism remains unclear. In this study, we investigated the role of FXR in atherosclerosis and NAFLD and the effect of peroxisome proliferator-activated receptor (PPAR) agonists in mouse models with FXR deficiency.
Methods
En face lipid accumulation analysis, liver histology, serum levels of glucose and lipids, and mRNA expression of genes related to lipid metabolism were compared between apolipoprotein E (ApoE)^−/− and ApoE^−/−FXR^−/− mice. The effects of PPARα and PPARγ agonists were also compared in both groups of mice.
Results
Compared with ApoE^−/− mice, ApoE^−/−FXR^−/− mice showed more severe atherosclerosis, hepatic steatosis, and higher levels of serum cholesterol, low-density lipoprotein cholesterol, and triglycerides, accompanied by increased mRNA expression of FAS, ApoC2, TNFα, IL-6 (liver), ATGL, TGH, HSL, and MGL (adipocytes), and decreased mRNA expressions of CPT2 (liver) and Tfam (skeletal muscle). Treatment with a PPARα agonist, but not with a PPARγ agonist, partly reversed atherosclerosis and hepatic steatosis, and decreased plasma triglyceride levels in the ApoE^−/−FXR^−/− mice, in association with increased mRNA expression of CD36 and FATP and decreased expression of ApoC2 and ApoC3 (liver).
Conclusion
Loss of FXR is associated with aggravation of atherosclerosis and hepatic steatosis in ApoE-deficient mice, which could be reversed by a PPARα agonist through induction of fatty acid uptake, β-oxidation, and triglyceride hydrolysis.

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

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

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Correlation between Ultrasound TI-RADS and Bethesda FNAC Scoring in Thyroid Lesions: A Retrospective Analysis
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Do Hyun Kim, Sung Won Kim, Mohammed Abdullah Basurrah, Jueun Lee, Se Hwan Hwang
American Journal of Roentgenology.2023; 220(6): 791. CrossRef
Diagnostic efficiency among Eu-/C-/ACR-TIRADS and S-Detect for thyroid nodules: a systematic review and network meta-analysis
Longtao Yang, Cong Li, Zhe Chen, Shaqi He, Zhiyuan Wang, Jun Liu
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Comparison of diagnostic performance of two ultrasound risk stratification systems for thyroid nodules: a systematic review and meta-analysis
Yun Jin Kang, Hee Sun Ahn, Gulnaz Stybayeva, Ju Eun Lee, Se Hwan Hwang
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Yun Jin Kang, Gulnaz Stybayeya, Ju Eun Lee, Se Hwan Hwang
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Thyroid
Association between Iodine Intake, Thyroid Function, and Papillary Thyroid Cancer: A Case-Control Study: Kyungsik Kim, Sun Wook Cho, Young Joo Park, Kyu Eun Lee, Dong-Wook Lee, Sue K. Park; Endocrinol Metab. 2021;36(4):790-799. Published online August 11, 2021; DOI: https://doi.org/10.3803/EnM.2021.1034

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Background
This study aimed to assess the effects of iodine intake, thyroid function, and their combined effect on the risk of papillary thyroid cancer (PTC) and papillary thyroid microcarcinoma (PTMC).
Methods
A case-control study was conducted including 500 community-based controls who had undergone a health check-up, and 446 overall PTC cases (209 PTC and 237 PTMC) from the Thyroid Cancer Longitudinal Study. Urinary iodine concentration (UIC), was used as an indicator of iodine intake, and serum for thyroid function. The risk of PTC and PTMC was estimated using unconditional logistic regression.
Results
Excessive iodine intake (UIC ≥220 μg/gCr) was associated with both PTC (odds ratio [OR], 18.13 95% confidence interval [CI], 8.87 to 37.04) and PTMC (OR, 8.02; 95% CI, 4.64 to 13.87), compared to adequate iodine intake (UIC, 85 to 219 μg/gCr). Free thyroxine (T4) levels ≥1.25 ng/dL were associated with PTC (OR, 1.97; 95% CI, 1.36 to 2.87) and PTMC (OR, 2.98; 95% CI, 2.01 to 4.41), compared to free T4 levels of 0.7 to 1.24 ng/dL. Individuals with excessive iodine intake and high free T4 levels had a greatly increased OR of PTC (OR, 43.48; 95% CI, 12.63 to 149.62), and PTMC (OR, 26.96; 95% CI, 10.26 to 70.89), compared to individuals with adequate iodine intake and low free T4 levels.
Conclusion
Excessive iodine intake using creatinine-adjusted UIC and high free T4 levels may have a synergistic effect on PTC and PTMC. Considering both iodine intake and thyroid function is important to assess PTC and PTMC risk.

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Thyroid
Clinicopathological Characteristics and Recurrence-Free Survival of Rare Variants of Papillary Thyroid Carcinomas in Korea: A Retrospective Study: Mijin Kim, Sun Wook Cho, Young Joo Park, Hwa Young Ahn, Hee Sung Kim, Yong Joon Suh, Dughyun Choi, Bu Kyung Kim, Go Eun Yang, Il-Seok Park, Ka Hee Yi, Chan Kwon Jung, Bo Hyun Kim; Endocrinol Metab. 2021;36(3):619-627. Published online June 10, 2021; DOI: https://doi.org/10.3803/EnM.2021.974

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Background
We aimed to evaluate the clinicopathological features and biological behaviors of Korean thyroid cancer patients with rare variants of papillary thyroid carcinoma (PTC) to address the ambiguity regarding the prognostic consequences of these variants.
Methods
We retrospectively reviewed the medical records of 5,496 patients who underwent thyroid surgery for PTC, between January and December 2012, in nine tertiary hospitals. Rare PTC variants included tall cell (TCV), columnar cell (CCV), diffuse sclerosing (DSV), cribriform-morular (CMV), solid (SV), hobnail, and Warthin-like variants. Recurrence-free survival (RFS) was defined as the time from the date of thyroidectomy until recurrence.
Results
Rare variants accounted for 1.1% (n=63) of the PTC patients; with 0.9% TCV, 0.02% CCV, 0.1% DSV, 0.1% CMV, and 0.1% SV. The mean age of patients and primary tumor size were 42.1±13.1 years and 1.3±0.9 cm, respectively. Extrathyroidal extension and cervical lymph node metastasis were observed in 38 (60.3%) and 37 (58.7%) patients, respectively. Ultrasonographic findings revealed typical malignant features in most cases. During a median follow-up of 7 years, 6.3% of patients experienced a locoregional recurrence. The 5-year RFS rates were 71.4% in patients with DSV or SV, 95.9% for TCV, or CCV, and 100% for other variants. DSV emerged an independent risk factor associated with shorter RFS.
Conclusion
In this multicenter Korean cohort, rare variants accounted for 1.1% of all PTC cases, with TCV being the most frequent subtype. DSV emerged as a significant prognostic factor for RFS.

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Thyroid
A Multicenter, Randomized, Controlled Trial for Assessing the Usefulness of Suppressing Thyroid Stimulating Hormone Target Levels after Thyroid Lobectomy in Low to Intermediate Risk Thyroid Cancer Patients (MASTER): A Study Protocol: Eun Kyung Lee, Yea Eun Kang, Young Joo Park, Bon Seok Koo, Ki-Wook Chung, Eu Jeong Ku, Ho-Ryun Won, Won Sang Yoo, Eonju Jeon, Se Hyun Paek, Yong Sang Lee, Dong Mee Lim, Yong Joon Suh, Ha Kyoung Park, Hyo-Jeong Kim, Bo Hyun Kim, Mijin Kim, Sun Wook Kim, Ka Hee Yi, Sue K. Park, Eun-Jae Jung, June Young Choi, Ja Seong Bae, Joon Hwa Hong, Kee-Hyun Nam, Young Ki Lee, Hyeong Won Yu, Sujeong Go, Young Mi Kang, MASTER study group; Endocrinol Metab. 2021;36(3):574-581. Published online May 26, 2021; DOI: https://doi.org/10.3803/EnM.2020.943

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Background
Postoperative thyroid stimulating hormone (TSH) suppression therapy is recommended for patients with intermediate- and high-risk differentiated thyroid cancer to prevent the recurrence of thyroid cancer. With the recent increase in small thyroid cancer cases, the extent of resection during surgery has generally decreased. Therefore, questions have been raised about the efficacy and long-term side effects of TSH suppression therapy in patients who have undergone a lobectomy.
Methods
This is a multicenter, prospective, randomized, controlled clinical trial in which 2,986 patients with papillary thyroid cancer are randomized into a high-TSH group (intervention) and a low-TSH group (control) after having undergone a lobectomy. The principle of treatment includes a TSH-lowering regimen aimed at TSH levels between 0.3 and 1.99 μIU/mL in the low-TSH group. The high-TSH group targets TSH levels between 2.0 and 7.99 μIU/mL. The dose of levothyroxine will be adjusted at each visit to maintain the target TSH level. The primary outcome is recurrence-free survival, as assessed by neck ultrasound every 6 to 12 months. Secondary endpoints include disease-free survival, overall survival, success rate in reaching the TSH target range, the proportion of patients with major cardiovascular diseases or bone metabolic disease, the quality of life, and medical costs. The follow-up period is 5 years.
Conclusion
The results of this trial will contribute to establishing the optimal indication for TSH suppression therapy in low-risk papillary thyroid cancer patients by evaluating the benefit and harm of lowering TSH levels in terms of recurrence, metabolic complications, costs, and quality of life.

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Effect of thyroid-stimulating hormone suppression on quality of life in thyroid lobectomy patients: interim analysis of a multicenter, randomized controlled trial in low- to intermediate-risk thyroid cancer patients (MASTER study)
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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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Gang Wei, Cao-xu Zhang, Yu Jing, Xia Chen, Huai-dong Song, Liu Yang
Chemosphere.2022; 308: 136354. CrossRef
Role of estrogen receptors in thyroid toxicity induced by mono (2-ethylhexyl) phthalate via endoplasmic reticulum stress: An in vitro mechanistic investigation
Qi Xu, Liting Zhou, Hyonju Ri, Xu Li, Xueting Zhang, Wen Qi, Lin Ye
Environmental Toxicology and Pharmacology.2022; 96: 104007. CrossRef

Review Articles

Thyroid
Best Achievements in Translational and Basic Thyroidology in 2020: Sun Wook Cho, Young Joo Park; Endocrinol Metab. 2021;36(1):36-40. Published online February 24, 2021; DOI: https://doi.org/10.3803/EnM.2021.104

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Abstract PDF PubReader ePub: This review discusses articles published in 2020 that presented noteworthy achievements in translational and basic thyroidology. Previously unresolved questions about thyroid hormone receptor actions and signaling mechanisms were answered using various novel in vitro and in vivo models. Using high resolution cryo-electron microscopy, the fine functional structure of thyroglobulin was demonstrated, and new insights into the pathogenesis of thyroid disease were achieved, with a focus on research into thyroid-disrupting chemicals and the gut microbiome. Novel therapeutic approaches were tried in the field of advanced thyroid cancer treatments.

Thyroid
Best Achievements in Clinical Thyroidology in 2020: Eun Kyung Lee, Young Joo Park; Endocrinol Metab. 2021;36(1):30-35. Published online February 24, 2021; DOI: https://doi.org/10.3803/EnM.2021.103

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This review highlights the most interesting research in thyroidology conducted in 2020. The publications of interest discussed below dealt with the following topics: thyroid dysfunction, risk of thyroid cancer, molecular diagnostics and new therapeutics for thyroid cancer, and thyroid disease in the coronavirus disease 2019 pandemic era.

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Compensation for iodine deficiency conditions with drugs based on duckweed substrate
M. Kh. Sadulaev, M. I. Usmanova, T. T. Tataev, A. M. Inderbiev, A. S.-A. Zhamalullayla, A. Salamova
BIO Web of Conferences.2023; 76: 03002. CrossRef
Use of long non-coding RNAs for the molecular diagnosis of papillary thyroid cancer
Daham Kim, Juyeon Yu, Jiwon Kim, Yoon-a Hwang, Jin Kyong Kim, Cheol Ryong Ku, Jung Hyun Yoon, Jin Young Kwak, Kee-Hyun Nam, Eun Jig Lee
Frontiers in Oncology.2022;[Epub] CrossRef
Ultrasound-Guided Fine-Needle Aspiration with or without Negative Pressure for Different Types of Thyroid Nodules
Qi Zhou, Wenjun Wu, Fang Wang, Xiaohua Gong, Xiaojun Chen
International Journal of General Medicine.2021; Volume 14: 5475. CrossRef

Original Articles

Clinical Study
Trends in the Diagnosis and Treatment of Patients with Medullary Thyroid Carcinoma in Korea: Hwa Young Ahn, Jae Eun Chae, Hyemi Moon, Junghyun Noh, Young Joo Park, Sin Gon Kim; Endocrinol Metab. 2020;35(4):811-819. Published online November 20, 2020; DOI: https://doi.org/10.3803/EnM.2020.709

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Background
Thyroid cancer is becoming increasingly common worldwide, but little is known about the epidemiology of medullary thyroid carcinoma (MTC). This study investigated the current status of the incidence and treatment of MTC using Korean National Health Insurance Service (NHIS) data for the entire Korean population from 2004 to 2016.
Methods
This study included 1,790 MTC patients identified from the NHIS database.
Results
The age-standardized incidence rate showed a slightly decreasing or stationary trend during the period, from 0.25 per 100,000 persons in 2004 to 0.19 in 2016. The average proportion of MTC among all thyroid cancers was 0.5%. For initial surgical treatment, 65.4% of patients underwent total thyroidectomy. After surgery, external-beam radiation therapy (EBRT) was performed in 10% of patients, a proportion that increased from 6.7% in 2004 to 11.0% in 2016. Reoperations were performed in 2.7% of patients (n=49) at a median of 1.9 years of follow-up (interquartile range, 1.2 to 3.4). Since November 2015, 25 (1.4%) patients with MTC were prescribed vandetanib by December 2016.
Conclusion
The incidence of MTC decreased slightly with time, and the proportion of patients who underwent total thyroidectomy was about 65%. EBRT, reoperation, and tyrosine kinase inhibitor therapy are additional treatments after initial surgery for advanced MTC in Korea.

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Digital Phenotyping of Rare Endocrine Diseases Across International Data Networks and the Effect of Granularity of Original Vocabulary
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Use of Glucagon-Like Peptide-1 Receptor Agonists Does Not Increase the Risk of Cancer in Patients with Type 2 Diabetes Mellitus
Mijin Kim, Seung Chan Kim, Jinmi Kim, Bo Hyun Kim
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Preoperative controlling nutritional status score for patients with medullary thyroid cancer
Mijin Kim, Hee Kyung Kim, Chae A. Kim, Meihua Jin, Min Ji Jeon, Ho-Cheol Kang, Dong Jun Lim, Eun Sook Kim, Byeong-Cheol Ahn, Won Gu Kim, Bo Hyun Kim
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Treatment and management of medullary thyroid microcarcinoma: a 10-year retrospective study from a single center
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Management of Giant Thyroid Tumors in Patients with Multiple Comorbidities in a Tertiary Head and Neck Surgery Center
Daniela Vrinceanu, Mihai Dumitru, Andreea Marinescu, Crenguta Serboiu, Gabriela Musat, Mihai Radulescu, Matei Popa-Cherecheanu, Catalina Ciornei, Felicia Manole
Biomedicines.2024; 12(10): 2204. CrossRef
MicroRNAs in thyroid cancer with focus on medullary thyroid carcinoma: potential therapeutic targets and diagnostic/prognostic markers and web based tools
ELHAM SHAKIBA, SETI BOROOMAND, SIMA KHERADMAND KIA, MEHDI HEDAYATI
Oncology Research.2024; 32(6): 1011. CrossRef
Big Data Research in the Field of Endocrine Diseases Using the Korean National Health Information Database
Sun Wook Cho, Jung Hee Kim, Han Seok Choi, Hwa Young Ahn, Mee Kyoung Kim, Eun Jung Rhee
Endocrinology and Metabolism.2023; 38(1): 10. CrossRef
Update on C-Cell Neuroendocrine Neoplasm: Prognostic and Predictive Histopathologic and Molecular Features of Medullary Thyroid Carcinoma
Chan Kwon Jung, Shipra Agarwal, Jen-Fan Hang, Dong-Jun Lim, Andrey Bychkov, Ozgur Mete
Endocrine Pathology.2023; 34(1): 1. CrossRef
Mouse Models to Examine Differentiated Thyroid Cancer Pathogenesis: Recent Updates
Hye Choi, Kwangsoon Kim
International Journal of Molecular Sciences.2023; 24(13): 11138. CrossRef
Partial preservation of the normal thyroid gland based on tumor diameter may be possible in small medullary thyroid carcinoma: a two-center 15-year retrospective study
Guiming Fu, Xiaoyi Li, Fengli Guo, Xianhui Ruan, Wei Zhang, Weijing Zhang, Yaping Zhang, Yibo Chen, Chunhua Li, Jin Chen, Xiangqian Zheng, Zhaohui Wang, Ming Gao
Frontiers in Oncology.2023;[Epub] CrossRef
Association of Socioeconomic Status With Long-Term Outcome in Survivors After Out-of-Hospital Cardiac Arrest: Nationwide Population-Based Longitudinal Study
Kyung Hun Yoo, Yongil Cho, Jaehoon Oh, Juncheol Lee, Byuk Sung Ko, Hyunggoo Kang, Tae Ho Lim, Sang Hwan Lee
JMIR Public Health and Surveillance.2023; 9: e47156. CrossRef
Preoperative identification of low-risk medullary thyroid carcinoma: potential application to reduce total thyroidectomy
Hyunju Park, Hyun Jin Ryu, Jung Heo, Man Ki Chung, Young Ik Son, Jung-Han Kim, Soo Yeon Hahn, Jung Hee Shin, Young Lyun Oh, Sun Wook Kim, Jae Hoon Chung, Jee Soo Kim, Tae Hyuk Kim
Scientific Reports.2023;[Epub] CrossRef
Clinical Characteristics, Surgical Management, and Prognostic Factors of Medullary Thyroid Carcinoma: A Retrospective, Single-Center Study
Xin Wu, Binglu Li, Chaoji Zheng
Technology in Cancer Research & Treatment.2022;[Epub] CrossRef
Understanding and Utilizing Claim Data from the Korean National Health Insurance Service (NHIS) and Health Insurance Review & Assessment (HIRA) Database for Research
Dae-Sung Kyoung, Hun-Sung Kim
Journal of Lipid and Atherosclerosis.2022; 11(2): 103. CrossRef
Unilateral Surgery for Medullary Thyroid Carcinoma: Seeking for Clinical Practice Guidelines
Daqi Zhang, Carla Colombo, Hui Sun, Hoon Yub Kim, Antonella Pino, Simone De Leo, Giacomo Gazzano, Luca Persani, Gianlorenzo Dionigi, Laura Fugazzola
Frontiers in Endocrinology.2022;[Epub] CrossRef
Total thyroidectomy vs thyroid lobectomy for localized medullary thyroid cancer in adults: A propensity-matched survival analysis
Weili Liang, Jinyuan Shi, Hui Zhang, Guixu Lv, Tiantian Wang, Yong Wang, Bin Lv, Luchuan Li, Qingdong Zeng, Lei Sheng
Surgery.2022; 172(5): 1385. CrossRef
Constitutive Cytomorphologic Features of Medullary Thyroid Carcinoma Using Different Staining Methods
Chih-Yi Liu, Chien-Chin Chen, Andrey Bychkov, Shipra Agarwal, Yun Zhu, Jen-Fan Hang, Chiung-Ru Lai, Hee Young Na, So Yeon Park, Weiwei Li, Zhiyan Liu, Deepali Jain, Ayana Suzuki, Mitsuyoshi Hirokawa, Noel Chia, Min En Nga, Tikamporn Jitpasutham, Somboon K
Diagnostics.2021; 11(8): 1396. CrossRef
Metastatic Lymph Node Ratio for Predicting Recurrence in Medullary Thyroid Cancer
Jinyoung Kim, Jun Park, Hyunju Park, Min Sun Choi, Hye Won Jang, Tae Hyuk Kim, Sun Wook Kim, Jae Hoon Chung
Cancers.2021; 13(22): 5842. CrossRef
A High Frequency of Lobectomy Instead of Total Thyroidectomy to Treat Medullary Thyroid Cancer in Korea: Data from the Korean National Health Insurance Service
Sun Wook Cho
Endocrinology and Metabolism.2020; 35(4): 784. CrossRef

Clinical Study
A Phase II Multi-Center, Non-Randomized, Parallel Group, Non-Inferiority Study to Compare the Efficacy of No Radioactive Iodine Remnant Ablation to Remnant Ablation Treatment in Low- to Intermediate-Risk of Papillary Thyroid Cancer: The MOREthyroid Trial Protocol: Eun Kyung Lee, You Jin Lee, Young Joo Park, Jae Hoon Moon, Ka Hee Yi, Koon Soon Kim, Joo Hee Lee, Sun Wook Cho, Jungnam Joo, Yul Hwangbo, Sujeong Go, Do Joon Park; Endocrinol Metab. 2020;35(3):571-577. Published online September 22, 2020; DOI: https://doi.org/10.3803/EnM.2020.681

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Background
Radioactive iodine (RAI) remnant ablation is recommended in patients with papillary thyroid cancer (PTC) and extrathyroidal extension or central lymph node metastasis. However, there exists little evidence about the necessity of remnant ablation in PTC patients with low- to intermediate-risk, those have been increasing in recent decades.
Methods
This multicenter, prospective, non-randomized, parallel group clinical trial will enroll 310 eligible patients with low- to intermediate-risk of thyroid cancer. Inclusion criteria are patients who recently underwent total thyroidectomy for PTC with 3 or less tumors of size 1≤ to ≤2 cm with no microscopic extension and N0/x, or size ≤2 cm with microscopic extension and/or N1a (number of lymph node ≤3, size of tumor foci ≤0.2 cm, and lymph node ratio <0.4). Patients choose to undergo RAI ablation (¹³¹I, dose 1.1 GBq) or diagnostic whole-body scan (DxWBS) (¹³¹I or ¹²³I, dose 0.074 to 0.222 GBq), followed by subsequent measurement of stimulated thyroglobulin (sTg) within 1 year. Survey for quality of life (QOL) will be performed at baseline and at 1 year after follow-up. The total enrollment period is 5 years, and patients will be followed up for 1 year. The primary endpoint is the non-inferiority of surgery alone to surgery with ablation in terms of biochemical remission (BCR) rate (sTg ≤2 ng/mL) without evidence of structural recurrence. The secondary endpoint was the difference of QOL.
Conclusion
This study will evaluate whether surgery alone achieves similar BCR and improved QOL compared to RAI ablation in patients with low- to intermediate-risk PTC within 1 year.

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Radioactive Iodine Therapy in Differentiated Thyroid Cancer: Summary of the Korean Thyroid Association Guidelines 2024 from Nuclear Medicine Perspective, Part-II
So Won Oh, Sohyun Park, Ari Chong, Keunyoung Kim, Ji-In Bang, Youngduk Seo, Chae Moon Hong, Sang-Woo Lee
Nuclear Medicine and Molecular Imaging.2025; 59(1): 8. CrossRef
Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Part I. Initial Management of Differentiated Thyroid Cancers - Chapter 6. Radioactive Iodine Treatment after Thyroidectomy 2024
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International Journal of Thyroidology.2024; 17(1): 97. CrossRef

Review Article

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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Role of TERT gene mutation in the pathogenesis of anaplastic thyroid carcinoma (Review)
Abdul-Mohsen Alhejaily, Omar Alhuzaim, Naji Aljohani, Doaa Alghamdi, Raneem Salem
Molecular and Clinical Oncology.2025; 23(2): 1. CrossRef
TERT Promoter C228T and C250T Hotspot Mutations Are Absent in BRAF V600E‐Positive Langerhans Cell Histiocytosis
Abdou Malik Da Silva, Zofia Hélias‐Rodzewicz, Irena Ungureanu, Jean‐François Emile
Cancer Medicine.2025;[Epub] CrossRef
Prognostic significance of BRAF V600E and TERT promoter mutations in radioiodine resistance and recurrence of differentiated thyroid cancer
Le Thi Tuyet Nhung, Nghiem Xuan Hoan, Dao Phuong Giang, Dang Trung Dung, Nguyen Thi Phuong, Ngo Thi Minh Hanh, Le Van Khanh, Ngo Thu Hang, Le Ngoc Ha, Hoang Van Tong
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Frequent BRAF V600E and TERT promoter‐mutated renal epithelial‐predominant Wilms tumours with metanephric features: a distinct subset within the Wilms tumour spectrum?
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Expanding the Morphologic and Molecular Spectrum of Spindle Cell Tumors Associated With TERT Fusions
Susan Swee‐Shan Hue, Carla Saoud, Dorukhan Bahceci, Liliana Villafania, Jamal Benhamida, Cristina R. Antonescu
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BRAFV600E/pTERT double mutated papillary thyroid cancers exhibit immune gene suppression
Ana-Maria Sigarteu Chindris, Michael Rivera, Yaohua Ma, Asha Nair, Yi Liu, Xue Wang, Brian M. Necela, Jennifer M. Kachergus, John D. Casler, Christopher Brett, Ana M. Rivas Mejia, Victor J. Bernet, John A. Copland, Keith L. Knutson, E. Aubrey Thompson, Ro
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SARS-CoV-2 Spike Protein Amplifies the Immunogenicity of Healthy Renal Epithelium in the Presence of Renal Cell Carcinoma
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Alexander T. Kikuchi, Sarah Umetsu, Nancy Joseph, Sanjay Kakar
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How limited molecular testing can also offer diagnostic and prognostic evaluation of thyroid nodules processed with liquid‐based cytology: Role of TERT promoter and BRAF V600E mutation analysis
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Original Article

Clinical Study
Subclinical Hypothyroidism Affects the Long-Term Outcomes of Patients Who Undergo Coronary Artery Bypass Grafting Surgery but Not Heart Valve Surgery: Hana Kim, Sung Hye Kong, Jae Hoon Moon, Sang Yoon Kim, Kay-Hyun Park, Jun Sung Kim, Joong Haeng Choh, Young Joo Park, Cheong Lim; Endocrinol Metab. 2020;35(2):308-318. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.308

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Background
The aim of this study was to determine the associations between subclinical hypothyroidism (SCH) and long-term cardiovascular outcomes after coronary artery bypass grafting (CABG) or heart valve surgery (HVS).
Methods
We retrospectively reviewed and compared all-cause mortality, cardiovascular mortality, and cardiovascular events in 461 patients who underwent CABG and 104 patients who underwent HVS.
Results
During a mean±standard deviation follow-up duration of 7.6±3.8 years, there were 187 all-cause deaths, 97 cardiovascular deaths, 127 major adverse cardiovascular events (MACE), 11 myocardial infarctions, one unstable angina, 70 strokes, 30 hospitalizations due to heart failure, 101 atrial fibrillation, and 33 coronary revascularizations. The incidence of all-cause mortality after CABG was significantly higher in patients with SCH (n=36, 55.4%) than in euthyroid patients (n=120, 30.3%), with a hazard ratio of 1.70 (95% confidence interval, 1.10 to 2.63; P=0.018) after adjustment for age, sex, current smoking status, body mass index, underlying diseases, left ventricular dysfunction, and emergency operation. Interestingly, low total triiodothyronine (T3) levels in euthyroid patients who underwent CABG were significantly associated with increased risks of all-cause mortality, cardiovascular mortality, and MACE, but those associations were not observed in HVS patients. Both free thyroxine and thyroid-stimulating hormone levels in euthyroid patients were not related with any cardiovascular outcomes in either the CABG or HVS group.
Conclusion
SCH or low total T3 might be associated with a poor prognosis after CABG, but not after HVS, implying that preoperative thyroid hormonal status may be important in ischemic heart disease patients.

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Review Articles

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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Validation of Diagnostic Utility of Washout CYFRA 21-1 in Lymph Node Metastasis of Thyroid Cancer
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Dabrafenib and Trametinib Therapy for Advanced Anaplastic Thyroid Cancer – Real-World Outcomes From UK Centres
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Thyroid
Bisphenols and Thyroid Hormone: Min Joo Kim, Young Joo Park; Endocrinol Metab. 2019;34(4):340-348. Published online December 23, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.4.340

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

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Original Articles

The Incidence of Thyroid Autoantibody in Subacute Thyroiditis and the Clinical Characteristics of Greeping Thyroiditis.: Jae Seok Jeon, Won Bae Kim, Hae Young Park, Young Joo Park, Hyun Kyung Chung, Sang Jeon Choi, Chan Soo Shin, Kyoung Soo Park, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee, Chang Soon Koh; J Korean Endocr Soc. 1996;11(4):438-446. Published online November 7, 2019

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Abstract PDF: Background
Subacute thyroiditis is a spontaneously resolving inflammatory disorder of thyroid gland, usually associated with painful goiter and short-lived thyrotoxicosis. Although its etiology is yet to be established, much evidence suggests viral infections and genetic factors play important roles. Usually, both lobes of thyroid gland are involved simultaneously, but in some patients one lobe is involved first and the other later(creeping thyroiditis), Thyroid autoantibodies which might appear probably due to inflammatory release of thyroid antigens, are found in a variable number of patients with subacute thyroiditis. However there have been few detailed reports on their incidence in Korean patients with subacute thyroiditis. So, we were to see the elinical characteristics of patients with subacute thyroiditis with special regards to the incidence of thyroid autoantibodies and to the incidence and characteristics of creeping thyroiditis, Methods: We reviewed the clinical records of 85 patients with subacute thyroiditis(7 men and 78 wornen, meam age of 43+9 years) who had visited the thyroid clinic in Seoul National University Hospital between 1986 and 1994. Results: At initial visit, the incidenees of thyroid autoantibodies were as follows: anti- microsomal antibody 7.8%, anti-thyroglobulin antibody 22.1%, and thyratropin binding inhibitor inununglobulin 6.3%. During the follow-up period, thyroid autoantibodies appeared most frequently between the first and the second month after initial visit. Compared to those with non-creeping thyroiditis, the patients with creeping thyroiditis(21.4%) had nonspecific systemic sy~rnptoms more frequently(89% vs. 42%, p<0.05). They required steroid therapy more ftequently(89% vs. 52%, p <0.05), and needed longer duration of treatment(9.3+6.2weeks vs, 4.7+3.7weeks, p<0.05). The incidence of abnormalities in liver function and the incidence of thyroid autoantibodies were higher in non-creeping thyroiditis group. Conclusion: In accordance with previous reports, thyroid autoantibodies were detected in only a small portion of Korean patients with subacute thyroiditis. Rather different clinical manifestations and different incidences of thyroid autoantibodies between ereeping group and non-creeping group suggest differences in the pathogenetic mechanisms between those two groups. However, there is need for further study to validate such observation and to elucidate the mechanisms.

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

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Background

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

Methods

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

Results

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

Conclusion

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

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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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Abstract PDF PubReader ePub

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 Articles

Thyroid
Associations between Hashimoto Thyroiditis and Clinical Outcomes of Papillary Thyroid Cancer: A Meta-Analysis of Observational Studies: Shinje Moon, Hye Soo Chung, Jae Myung Yu, Hyung Joon Yoo, Jung Hwan Park, Dong Sun Kim, Young Joo Park; Endocrinol Metab. 2018;33(4):473-484. Published online November 30, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.4.473

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Background

Epidemiological studies have suggested an association between Hashimoto thyroiditis (HT) and papillary thyroid cancer (PTC) development. Other studies, however, have reported a protective role of HT against PTC progression. Through this updated meta-analysis, we aimed to clarify the effects of HT on the progression of PTC.

Methods

We searched citation databases, including PubMed and Embase, for relevant studies from inception to September 2017. From these studies, we calculated the pooled odds ratios (ORs) of clinicopathologic features and the relative risk (RR) of PTC recurrence with 95% confidence intervals (CIs) using the Mantel-Haenszel method. Additionally, the Higgins I² statistic was used to test for heterogeneity.

Results

The meta-analysis included 71 published studies with 44,034 participants, among whom 11,132 had HT. We observed negative associations between PTC with comorbid HT and extrathyroidal extension (OR, 0.74; 95% CI, 0.68 to 0.81), lymph node metastasis (OR, 0.82; 95% CI, 0.72 to 0.94), distant metastasis (OR, 0.49; 95% CI, 0.32 to 0.76), and recurrence (RR, 0.50; 95% CI, 0.41 to 0.61).

Conclusion

In this meta-analysis, PTC patients with HT appeared to exhibit more favorable clinicopathologic characteristics and a better prognosis than those without HT.

Citations

Citations to this article as recorded by

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PLOS ONE.2020; 15(6): e0234566. CrossRef
Hashimoto's thyroiditis as a risk factor for thyroid cancer
Ulla Feldt-Rasmussen
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Predictive Factors of Recurrence for Multifocal Papillary Thyroid Microcarcinoma With Brafv600e Mutation: A Single Center Study of 1,207 Chinese Patients
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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

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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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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.

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Review Article

Thyroid
Genome-Wide Association Studies of Autoimmune Thyroid Diseases, Thyroid Function, and Thyroid Cancer: Yul Hwangbo, Young Joo Park; Endocrinol Metab. 2018;33(2):175-184. Published online June 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.2.175

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Thyroid diseases, including autoimmune thyroid diseases and thyroid cancer, are known to have high heritability. Family and twin studies have indicated that genetics plays a major role in the development of thyroid diseases. Thyroid function, represented by thyroid stimulating hormone (TSH) and free thyroxine (T4), is also known to be partly genetically determined. Before the era of genome-wide association studies (GWAS), the ability to identify genes responsible for susceptibility to thyroid disease was limited. Over the past decade, GWAS have been used to identify genes involved in many complex diseases, including various phenotypes of the thyroid gland. In GWAS of autoimmune thyroid diseases, many susceptibility loci associated with autoimmunity (human leukocyte antigen [HLA], protein tyrosine phosphatase, non-receptor type 22 [PTPN22], cytotoxic T-lymphocyte associated protein 4 [CTLA4], and interleukin 2 receptor subunit alpha [IL2RA]) or thyroid-specific genes (thyroid stimulating hormone receptor [TSHR] and forkhead box E1 [FOXE1]) have been identified. Regarding thyroid function, many susceptibility loci for levels of TSH and free T4 have been identified through genome-wide analyses. In GWAS of differentiated thyroid cancer, associations at FOXE1, MAP3K12 binding inhibitory protein 1 (MBIP)-NK2 homeobox 1 (NKX2-1), disrupted in renal carcinoma 3 (DIRC3), neuregulin 1 (NRG1), and pecanex-like 2 (PCNXL2) have been commonly identified in people of European and Korean ancestry, and many other susceptibility loci have been found in specific populations. Through GWAS of various thyroid-related phenotypes, many susceptibility loci have been found, providing insights into the pathogenesis of thyroid diseases and disease co-clustering within families and individuals.

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Original Articles

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

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Abstract PDF PubReader ePub

Background

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

Methods

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

Results

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

Conclusion

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

Citations

Citations to this article as recorded by

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

Thyroid
Validity and Reliability of the Korean Version of the Hyperthyroidism Symptom Scale: Jie-Eun Lee, Dong Hwa Lee, Tae Jung Oh, Kyoung Min Kim, Sung Hee Choi, Soo Lim, Young Joo Park, Do Joon Park, Hak Chul Jang, Jae Hoon Moon; Endocrinol Metab. 2018;33(1):70-78. Published online March 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.1.70

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Background

Thyrotoxicosis is a common disease resulting from an excess of thyroid hormones, which affects many organ systems. The clinical symptoms and signs are relatively nonspecific and can vary depending on age, sex, comorbidities, and the duration and cause of the disease. Several symptom rating scales have been developed in an attempt to assess these symptoms objectively and have been applied to diagnosis or to evaluation of the response to treatment. The aim of this study was to assess the reliability and validity of the Korean version of the hyperthyroidism symptom scale (K-HSS).

Methods

Twenty-eight thyrotoxic patients and 10 healthy subjects completed the K-HSS at baseline and after follow-up at Seoul National University Bundang Hospital. The correlation between K-HSS scores and thyroid function was analyzed. K-HSS scores were compared between baseline and follow-up in patient and control groups. Cronbach's α coefficient was calculated to demonstrate the internal consistency of K-HSS.

Results

The mean age of the participants was 34.7±9.8 years and 13 (34.2%) were men. K-HSS scores demonstrated a significant positive correlation with serum free thyroxine concentration and decreased significantly with improved thyroid function. K-HSS scores were highest in subclinically thyrotoxic subjects, lower in patients who were euthyroid after treatment, and lowest in the control group at follow-up, but these differences were not significant. Cronbach's α coefficient for the K-HSS was 0.86.

Conclusion

The K-HSS is a reliable and valid instrument for evaluating symptoms of thyrotoxicosis in Korean patients.

Citations

Citations to this article as recorded by

Effect of thyroid-stimulating hormone suppression on quality of life in thyroid lobectomy patients: interim analysis of a multicenter, randomized controlled trial in low- to intermediate-risk thyroid cancer patients (MASTER study)
Ja Kyung Lee, Eu Jeong Ku, Su-jin Kim, Woochul Kim, Jae Won Cho, Kyong Yeun Jung, Hyeong Won Yu, Yea Eun Kang, Mijin Kim, Hee Kyung Kim, Junsun Ryu, June Young Choi
Annals of Surgical Treatment and Research.2024; 106(1): 19. CrossRef
Effect of increased levothyroxine dose on depressive mood in older adults undergoing thyroid hormone replacement therapy
Jae Hoon Moon, Ji Won Han, Tae Jung Oh, Sung Hee Choi, Soo Lim, Ki Woong Kim, Hak Chul Jang
Clinical Endocrinology.2020; 93(2): 196. CrossRef
Clinical Feasibility of Monitoring Resting Heart Rate Using a Wearable Activity Tracker in Patients With Thyrotoxicosis: Prospective Longitudinal Observational Study
Jie-Eun Lee, Dong Hwa Lee, Tae Jung Oh, Kyoung Min Kim, Sung Hee Choi, Soo Lim, Young Joo Park, Do Joon Park, Hak Chul Jang, Jae Hoon Moon
JMIR mHealth and uHealth.2018; 6(7): e159. CrossRef

Endocrine Research
Macrophage Densities Correlated with CXC Chemokine Receptor 4 Expression and Related with Poor Survival in Anaplastic Thyroid Cancer: Dae In Kim, Eunyoung Kim, Young A Kim, Sun Wook Cho, Jung Ah Lim, Young Joo Park; Endocrinol Metab. 2016;31(3):469-475. Published online August 2, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.3.469

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Background

Tumor associated macrophages (TAMs) and CXC chemokine receptor 4 (CXCR4) have emerged as potential biomarkers in various human cancers. The aims of this study were to investigate the clinical characteristics of anaplastic thyroid cancer (ATC) patients according to the TAM numbers in the tumor tissue, and to evaluate the associations between CXCR4 expressions and macrophage densities in ATC tumor microenvironment.

Methods

Total 14 ATC samples from thyroid tissue microarray were used. Immunohistochemical staining was performed using anti-CD163 and anti-CXCR4 antibodies. According to the immunoreactivity of CD163, all subjects were divided into two groups: low-CD163 (n=8) and high-CD163 (n=6) groups.

Results

The mean diagnostic age was 65±7 years and the median tumor size was 4.3 cm, ranging 2.5 to 15 cm. Clinicopathological characteristics were not significantly different between low-CD163 and high-CD163 groups, while age of diagnosis was younger in high-CD163 group than that of low-CD163 group with marginal significance (56.9±5.5 years vs. 67.5±6.8 years, P=0.09). However, overall survival was significantly reduced in high-CD163 group (5.5 months [range, 1 to 10]) compared with low-CD163 groups (8.8 months [range, 6 to 121); log-rank test, P=0.0443). Moreover, high-CD163 group showed strong CXCR4 expressions in both cancer and stromal compartments, while low-CD163 group showed relatively weak, stromal-dominant CXCR4 expressions. Additionally, CD163 and CXCR4 expressions showed a strong positive correlation (γ²=0.432, P=0.013).

Conclusion

Increased number of TAMs showed poor overall survival in ATC, suggesting TAMs are potentially a prognostic biomarker for ATC. CXCR4 expression was significantly correlated with CD163-positive TAM densities, which suggest the possible role of CXCR4 in TAM recruitments.

Citations

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Endocrine Research
Thyroid Hormone Regulates the mRNA Expression of Small Heterodimer Partner through Liver Receptor Homolog-1: Hwa Young Ahn, Hwan Hee Kim, Ye An Kim, Min Kim, Jung Hun Ohn, Sung Soo Chung, Yoon-Kwang Lee, Do Joon Park, Kyong Soo Park, David D. Moore, Young Joo Park; Endocrinol Metab. 2015;30(4):584-592. Published online December 31, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.4.584

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Background

Expression of hepatic cholesterol 7α-hydroxylase (CYP7A1) is negatively regulated by orphan nuclear receptor small heterodimer partner (SHP). In this study, we aimed to find whether thyroid hormone regulates SHP expression by modulating the transcriptional activities of liver receptor homolog-1 (LRH-1).

Methods

We injected thyroid hormone (triiodothyronine, T3) to C57BL/6J wild type. RNA was isolated from mouse liver and used for microarray analysis and quantitative real-time polymerase chain reaction (PCR). Human hepatoma cell and primary hepatocytes from mouse liver were used to confirm the effect of T3 in vitro. Promoter assay and electrophoretic mobility-shift assay (EMSA) were also performed using human hepatoma cell line

Results

Initial microarray results indicated that SHP expression is markedly decreased in livers of T3 treated mice. We confirmed that T3 repressed SHP expression in the liver of mice as well as in mouse primary hepatocytes and human hepatoma cells by real-time PCR analysis. LRH-1 increased the promoter activity of SHP; however, this increased activity was markedly decreased after thyroid hormone receptor β/retinoid X receptor α/T3 administration. EMSA revealed that T3 inhibits specific LRH-1 DNA binding.

Conclusion

We found that thyroid hormone regulates the expression of SHP mRNA through interference with the transcription factor, LRH-1.

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Review Article

Thyroid
Mutation Profile of Well-Differentiated Thyroid Cancer in Asians: Young Shin Song, Jung Ah Lim, Young Joo Park; Endocrinol Metab. 2015;30(3):252-262. Published online September 22, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.3.252

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Recent advances in molecular diagnostics have led to significant insights into the genetic basis of thyroid tumorigenesis. Among the mutations commonly seen in thyroid cancers, the vast majority are associated with the mitogen-activated protein kinase pathway. B-Raf proto-oncogene (BRAF) mutations are the most common mutations observed in papillary thyroid cancers (PTCs), followed by RET/PTC rearrangements and RAS mutations, while follicular thyroid cancers are more likely to harbor RAS mutations or PAX8/peroxisome proliferator-activated receptor γ (PPARγ) rearrangements. Beyond these more common mutations, alterations in the telomerase reverse transcriptase (TERT) promoter have recently been associated with clinicopathologic features, disease prognosis, and tumorigenesis in thyroid cancer. While the mutations underlying thyroid tumorigenesis are well known, the frequency of these mutations is strongly associated with geography, with clear differences reported between Asian and Western countries. Of particular interest is the prevalence of BRAF mutations, with Korean patients exhibiting the highest rate of BRAF-associated thyroid cancers in the world. Here, we review the prevalence of each of the most common mutations in Asian and Western countries, and identify the characteristics of well-differentiated thyroid cancer in Asians.

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Original Article

Thyroid
The Frequency and Clinical Implications of the BRAF^V600E Mutation in Papillary Thyroid Cancer Patients in Korea Over the Past Two Decades: A Ram Hong, Jung Ah Lim, Tae Hyuk Kim, Hoon Sung Choi, Won Sang Yoo, Hye Sook Min, Jae Kyung Won, Kyu Eun Lee, Kyeong Cheon Jung, Do Joon Park, Young Joo Park; Endocrinol Metab. 2014;29(4):505-513. Published online December 29, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.4.505

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Background

Over the past several decades, there has been a rapid worldwide increase in the prevalence of papillary thyroid cancer (PTC) as well as a number of changes in the clinicopathological characteristics of this disease. BRAF^V600E, which is a mutation of the proto-oncogene BRAF, has become the most frequent genetic mutation associated with PTC, particularly in Korea. Thus, the present study investigated whether the prevalence of the BRAF^V600E mutation has increased over the past two decades in the Korean population and whether various PTC-related clinicopathological characteristics have changed.

Methods

The present study included 2,624 patients who underwent a thyroidectomy for PTC during two preselected periods; 1995 to 2003 and 2009 to 2012. The BRAF^V600E mutation status of each patient was confirmed using the polymerase chain reaction-restriction fragment length polymorphism method or by the direct sequencing of DNA.

Results

The prevalence of the BRAF^V600E mutation in Korean PTC patients increased from 62.2% to 73.7% (P=0.001) over the last two decades. Additionally, there was a greater degree of extrathyroidal extension (ETE) and lymph node metastasis in 2009 to 2012 patients with the BRAF^V600E mutation and a higher frequency of thyroiditis and follicular variant-PTC in 2009 to 2012 patients with wild-type BRAF. However, only the frequency of ETE was significantly higher in 1995 to 2003 patients with the BRAF^V600E mutation (P=0.047). Long-term recurrence rates during a 10-year median follow-up did not differ based on BRAF^V600E mutation status.

Conclusion

The BRAF^V600E mutation rate in Korean PTC patients has been persistently high (approximately 70%) over the past two decades and continues to increase. The present findings demonstrate that BRAF^V600E-positive PTC was associated with more aggressive clinicopathological features, especially in patients who were recently diagnosed, suggesting that BRAF^V600E mutation status may be a useful prognostic factor for PTC in patients recently diagnosed with this disease.

Citations

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Case Report

Thyroid
Medullary Thyroid Carcinoma with Ectopic Adrenocorticotropic Hormone Syndrome: Hong Seok Choi, Min Joo Kim, Chae Ho Moon, Jong Ho Yoon, Ha Ra Ku, Geon Wook Kang, Im Il Na, Seung-Sook Lee, Byung-Chul Lee, Young Joo Park, Hong Il Kim, Yun Hyi Ku; Endocrinol Metab. 2014;29(1):96-100. Published online March 14, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.1.96

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Ectopic adrenocorticotropic hormone (ACTH) syndrome is caused most frequently by a bronchial carcinoid tumor or by small cell lung cancer. Medullary thyroid carcinoma (MTC) is a rare etiology of ectopic ACTH syndrome. We describe a case of Cushing syndrome due to ectopic ACTH production from MTC in a 48-year-old male. He was diagnosed with MTC 14 years ago and underwent total thyroidectomy, cervical lymph node dissection and a series of metastasectomies. MTC was confirmed by the pathological examination of the thyroid and metastatic mediastinal lymph node tissues. Two years after his last surgery, he developed Cushingoid features, such as moon face and central obesity, accompanied by uncontrolled hypertension and new-onset diabetes. The laboratory results were compatible with ectopic ACTH syndrome. A bilateral adrenalectomy improved the clinical and laboratory findings that were associated with Cushing syndrome. This is the first confirmed case of ectopic ACTH syndrome caused by MTC in Korea.

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Review Article

Thyroid
Prevalence and Risk Factors of Subclinical Thyroid Disease: Ye An Kim, Young Joo Park; Endocrinol Metab. 2014;29(1):20-29. Published online March 14, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.1.20

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Abstract PDF PubReader

Subclinical thyroid disease is defined biochemically by an abnormal thyrotropin (TSH) level and normal serum-free thyroxine level. The prevalence of this condition varies according to the reference range for TSH and geographic or demographic factors. Recently, several studies, including our community-based cohort studies, have reported on the incidence of subclinical thyroid disease in Korea. Using these studies, we reviewed the prevalence and risk factors of subclinical thyroid disease, focusing on subclinical hypothyroidism.

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Original Article

Thyroid
The Expression of Tumor-Associated Macrophages in Papillary Thyroid Carcinoma: Seunghwan Kim, Sun Wook Cho, Hye Sook Min, Kang Min Kim, Gye Jeong Yeom, Eun Young Kim, Kyu Eun Lee, Yeo Gyu Yun, Do Joon Park, Young Joo Park; Endocrinol Metab. 2013;28(3):192-198. Published online September 13, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.3.192

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Abstract PDF PubReader

Background

Tumor-associated macrophages (TAMs) play a tumorigenic role related to advanced staging and poor prognosis in many human cancers including thyroid cancers. Yet, a functional role of TAMs in papillary thyroid carcinoma (PTC) has not been established. The aim of this study was to investigate TAM expression in human PTC with lymph node (LN) metastasis.

Methods

Thirty-six patients who underwent surgery after being diagnosed with PTC with LN metastasis were included. Primary tumor tissues were immunohistochemically stained with an anti-CD68 antibody and clinical characteristics according to TAM density were evaluated.

Results

The TAM densities (CD68⁺ cells) varied from 5% to 70%, in all tumor areas, while few cells were stained in adjacent normal tissues. TAMs were identified as CD68⁺ cells with thin, elongated cytoplasmic extensions that formed a canopy structure over tumor cells. Comparing clinicopathologic characteristics between tumors with low (<25%) and high (25% to 70%) TAM densities, primary tumors were larger in the high density group than in the low density group (2.0±0.1 vs. 1.5±0.1; P=0.009).

Conclusion

TAMs were identified in primary PTC tumors with LN metastasis and higher TAM densities were related to larger tumor sizes, suggesting a tumorigenic role of TAMs in human PTCs.

Citations

Citations to this article as recorded by

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