Endocrinology and Metabolism

Original Articles

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

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

Thyroid
Prognostic Roles of Inflammatory Biomarkers in Radioiodine-Refractory Thyroid Cancer Treated with Lenvatinib: Chae A Kim, Mijin Kim, Meihua Jin, Hee Kyung Kim, Min Ji Jeon, Dong Jun Lim, Bo Hyun Kim, Ho-Cheol Kang, Won Bae Kim, Dong Yeob Shin, Won Gu Kim; Endocrinol Metab. 2024;39(2):334-343. Published online April 4, 2024; DOI: https://doi.org/10.3803/EnM.2023.1854

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Background
Inflammatory biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR), serve as valuable prognostic indicators in various cancers. This multicenter, retrospective cohort study assessed the treatment outcomes of lenvatinib in 71 patients with radioactive iodine (RAI)-refractory thyroid cancer, considering the baseline inflammatory biomarkers.
Methods
This study retrospectively included patients from five tertiary hospitals in Korea whose complete blood counts were available before lenvatinib treatment. Progression-free survival (PFS) and overall survival (OS) were evaluated based on the median value of inflammatory biomarkers.
Results
No significant differences in baseline characteristics were observed among patients grouped according to the inflammatory biomarkers, except for older patients with a higher-than-median NLR (≥2) compared to their counterparts with a lower NLR (P= 0.01). Patients with a higher-than-median NLR had significantly shorter PFS (P=0.02) and OS (P=0.017) than those with a lower NLR. In multivariate analysis, a higher-than-median NLR was significantly associated with poor OS (hazard ratio, 3.0; 95% confidence interval, 1.24 to 7.29; P=0.015). However, neither the LMR nor the PLR was associated with PFS. A higher-than-median LMR (≥3.9) was significantly associated with prolonged OS compared to a lower LMR (P=0.036). In contrast, a higher-than-median PLR (≥142.1) was associated with shorter OS compared to a lower PLR (P=0.039).
Conclusion
Baseline inflammatory biomarkers can serve as predictive indicators of PFS and OS in patients with RAI-refractory thyroid cancer treated with lenvatinib.

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Nomogram Model for Prognosis of Distant Metastatic DTC Based on Inflammatory and Clinicopathological Factors
Chenghui Lu, Guoqiang Wang, Zengmei Si, Fengqi Li, Xinfeng Liu, Na Han, Congcong Wang, Jiao Li, Xufu Wang
Journal of the Endocrine Society.2025;[Epub] CrossRef

Corrigendum

Miscellaneous
Corrigendum: Correction of Acknowledgments. Protocol for a Korean Multicenter Prospective Cohort Study of Active Surveillance or Surgery (KoMPASS) in Papillary Thyroid Microcarcinoma: Min Ji Jeon, Yea Eun Kang, Jae Hoon Moon, Dong Jun Lim, Chang Yoon Lee, Yong Sang Lee, Sun Wook Kim, Min-Hee Kim, Bo Hyun Kim, Ho-Cheol Kang, Minho Shong, Sun Wook Cho, Won Bae Kim; Endocrinol Metab. 2022;37(1):181-182. Published online February 28, 2022; DOI: https://doi.org/10.3803/EnM.2022.104; Corrects: Endocrinol Metab 2021;36(2):359

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Risk of thyroid cancer associated with glucagon‐like peptide‐1 receptor agonists and dipeptidyl peptidase‐4 inhibitors in patients with type 2 diabetes: A population‐based cohort study
Sungho Bea, Heejun Son, Jae Hyun Bae, Sun Wook Cho, Ju‐Young Shin, Young Min Cho
Diabetes, Obesity and Metabolism.2024; 26(1): 108. CrossRef

Original Article

Thyroid
Clinical Characteristics and Prognosis of Coexisting Thyroid Cancer in Patients with Graves’ Disease: A Retrospective Multicenter Study: Jee Hee Yoon, Meihua Jin, Mijin Kim, A Ram Hong, Hee Kyung Kim, Bo Hyun Kim, Won Bae Kim, Young Kee Shong, Min Ji Jeon, Ho-Cheol Kang; Endocrinol Metab. 2021;36(6):1268-1276. Published online November 26, 2021; DOI: https://doi.org/10.3803/EnM.2021.1227

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Background
The association between Graves’ disease (GD) and co-existing thyroid cancer is still controversial and most of the previously reported data have been based on surgically treated GD patients. This study investigated the clinicopathological findings and prognosis of concomitant thyroid cancer in GD patients in the era of widespread application of ultrasonography.
Methods
Data of GD patients who underwent thyroidectomy for thyroid cancer between 2010 and 2019 in three tertiary hospitals in South Korea (Asan Medical Center, Chonnam National University Hwasun Hospital, and Pusan National University Hospital) were collected and analyzed retrospectively. In the subgroup analysis, aggressiveness and clinical outcomes of thyroid cancer were compared nodular GD and non-nodular GD groups according to the presence or absence of the thyroid nodules other than thyroid cancer (index nodules).
Results
Of the 15,159 GD patients treated at the hospitals during the study period, 262 (1.7%) underwent thyroidectomy for coexisting thyroid cancer. Eleven patients (4.2%) were diagnosed with occult thyroid cancer and 182 patients (69.5%) had microcarcinomas. No differences in thyroid cancer aggressiveness, ultrasonographic findings, or prognosis were observed between the nodular GD and non-nodular GD groups except the cancer subtype. In the multivariate analysis, only lymph node (LN) metastasis was an independent prognostic factor for recurrent/persistent disease of thyroid cancer arising in GD (P=0.020).
Conclusion
The prevalence of concomitant thyroid cancer in GD patients was considerably lower than in previous reports. The clinical outcomes of thyroid cancer in GD patients were also excellent but, more cautious follow-up is necessary for patients with LN metastasis in the same way as for thyroid cancer in non-GD patients.

Citations

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Incidental Thyroid Cancer in Patients With Graves’ Disease: Not as Rare as We Previously Believed
Shaidy Moronta, Lauren Slattery, Rongzhi Wang, Fiemu Nwariaku, Jessica Liu McMullin
Journal of Surgical Research.2025; 308: 122. CrossRef
Comparison of Surgical Outcomes of Transoral Versus Open Thyroidectomy for Graves Disease
Suo-Hsien Wang, Wu-Po Chao, Ta-You Lo, Soh-Ching Ng, Yu-Hsien Chen
Surgical Laparoscopy, Endoscopy & Percutaneous Techniques.2024; 34(2): 150. CrossRef
Characterization of Immune Infiltrate Along the Leading Edge of Differentiated Thyroid Cancer
Anupam Kotwal, Krysten Vance, Kemal Hajric, Ana Yuil-Valdes, Benjamin Swanson, Ernesto Martinez Duarte, Oleg Shats, Michael Hollingsworth, Hamid Band, Whitney Goldner
Thyroid®.2024; 34(8): 999. CrossRef
The Role of Risk Factors for the Progression of Patients with T1b-T2 Papillary Thyroid Carcinoma (PC) during Long-Term Follow-Up
Andrea Marongiu, Susanna Nuvoli, Andrea De Vito, Antonio Mura, Sonia Vargiu, Angela Spanu, Giuseppe Madeddu
Journal of Clinical Medicine.2024; 13(18): 5373. CrossRef
Outcomes of Surgical Treatment for Graves’ Disease: A Single-Center Experience of 216 Cases
Hanxing Sun, Hui Tong, Xiaohui Shen, Haoji Gao, Jie Kuang, Xi Chen, Qinyu Li, Weihua Qiu, Zhuoran Liu, Jiqi Yan
Journal of Clinical Medicine.2023; 12(4): 1308. CrossRef
Cancer and Mortality Risks of Graves’ Disease in South Korea Based on National Data from 2010 to 2019
Young Ju Choi, Kyungdo Han, Won Kyoung Cho, Min Ho Jung, Byung-Kyu Suh
Clinical Epidemiology.2023; Volume 15: 535. CrossRef
Risk and Prognosis of Thyroid Cancer in Patients with Graves’ Disease: An Umbrella Review
Marco Palella, Francesca Maria Giustolisi, Adriana Modica Fiascaro, Martina Fichera, Antonella Palmieri, Rossella Cannarella, Aldo E. Calogero, Margherita Ferrante, Maria Fiore
Cancers.2023; 15(10): 2724. CrossRef
Characteristics, staging and outcomes of differentiated thyroid cancer in patients with and without Graves’ disease
Chaitra Gopinath, Hanna Crow, Sujata Panthi, Leonidas Bantis, Kenneth D. Burman, Chitra Choudhary
Journal of Clinical & Translational Endocrinology.2023; 33: 100321. CrossRef
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
Endocrinology and Metabolism.2023; 38(4): 436. CrossRef
Hashimoto’s Thyroiditis and Papillary Thyroid Carcinoma: A Follow-Up Study in Patients with Absence of Aggressive Risk Factors at the Surgery of the Primary Tumor
Andrea Marongiu, Susanna Nuvoli, Andrea De Vito, Sonia Vargiu, Angela Spanu, Giuseppe Madeddu
Diagnostics.2023; 13(19): 3068. CrossRef
Table of Contents

Clinical Thyroidology.2022; 34(2): 48. CrossRef
Predisposition to and Prognosis of Thyroid Cancer May Not Be Affected by Graves’ Disease, But Some Questions Still Remain
Yanrui Huang, Haixia Guan
Clinical Thyroidology.2022; 34(2): 59. CrossRef
A Comparative Follow-Up Study of Patients with Papillary Thyroid Carcinoma Associated or Not with Graves’ Disease
Andrea Marongiu, Susanna Nuvoli, Andrea De Vito, Maria Rondini, Angela Spanu, Giuseppe Madeddu
Diagnostics.2022; 12(11): 2801. CrossRef
An unusual case of papillary thyroid carcinoma presenting as Graves’ disease
Pooja Tiwari, Uma Kaimal Saikia, Abhamoni Baro, Ashok Krishna Bhuyan
Thyroid Research and Practice.2022; 19(1): 47. CrossRef
An unusual case of papillary thyroid carcinoma presenting as Graves’ disease
Pooja Tiwari, Uma Kaimal Saikia, Abhamoni Baro, Ashok Krishna Bhuyan
Thyroid Research and Practice.2021; 18(3): 129. CrossRef

Editorial

Thyroid
Comparison of Thyroid Imaging Reporting and Data Systems in Malignancy Risk Stratification of Indeterminate Thyroid Nodules: Bo Hyun Kim; Endocrinol Metab. 2021;36(5):974-976. Published online October 28, 2021; DOI: https://doi.org/10.3803/EnM.2021.1287

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Original Articles

Thyroid
Clinicopathological Characteristics and Disease-Free Survival in Patients with Hürthle Cell Carcinoma: A Multicenter Cohort Study in South Korea: Meihua Jin, Eun Sook Kim, Bo Hyun Kim, Hee Kyung Kim, Yea Eun Kang, Min Ji Jeon, Tae Yong Kim, Ho-Cheol Kang, Won Bae Kim, Young Kee Shong, Mijin Kim, Won Gu Kim; Endocrinol Metab. 2021;36(5):1078-1085. Published online October 28, 2021; DOI: https://doi.org/10.3803/EnM.2021.1151

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

Citations

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Prognostic impact of fibrosclerotic changes in non-papillary, non-anaplastic, follicular cell-derived thyroid carcinomas
Giulia Orlando, Giulia Capella, Giulia Vocino Trucco, Elena Vissio, Jasna Metovic, Francesca Maletta, Marco Volante, Mauro Papotti
Virchows Archiv.2025;[Epub] CrossRef
Molecular Alterations and Comprehensive Clinical Management of Oncocytic Thyroid Carcinoma
Lindsay A. Bischoff, Ian Ganly, Laura Fugazzola, Erin Buczek, William C. Faquin, Bryan R. Haugen, Bryan McIver, Caitlin P. McMullen, Kate Newbold, Daniel J. Rocke, Marika D. Russell, Mabel Ryder, Peter M. Sadow, Eric Sherman, Maisie Shindo, David C. Shonk
JAMA Otolaryngology–Head & Neck Surgery.2024; 150(3): 265. CrossRef
Oncocytic carcinoma of the thyroid: Conclusions from a 20‐year patient cohort
Nelson R. Gruszczynski, Shahzeb S. Hasan, Ana G. Brennan, Julian De La Chapa, Adithya S. Reddy, David N. Martin, Prem P. Batchala, Edward B. Stelow, Eric M. Dowling, Katherine L. Fedder, Jonathan C. Garneau, David C. Shonka
Head & Neck.2024; 46(8): 2042. CrossRef
Oncocytic cell carcinoma of the thyroid with TERT promoter mutation presenting as asphyxia in an elderly: a case report
Xiqian Wang, Yingao Liu, Lijie Chen, Jie Zhang, Ruoyu Jiang, Lei Zhang, Han Yan, Jie Zhang
Frontiers in Endocrinology.2024;[Epub] CrossRef
Clinical Considerations of Oncocytic Thyroid Cancer: A Review
Soo Young Kim
Journal of Endocrine Surgery.2024; 24(3): 49. CrossRef
Mitochondrial Proteome Defined Molecular Pathological Characteristics of Oncocytic Thyroid Tumors
Lu Li, Likun Zhang, Wenhao Jiang, Zhiqiang Gui, Zhihong Wang, Hao Zhang, Yi He, Yi Zhu, Tiannan Guo, Haixia Guan, Zhiyan Liu, Yaoting Sun, Jianqing Gao
Endocrine Pathology.2024; 35(4): 442. CrossRef
Hurthle cell carcinoma: a rare variant of thyroid malignancy – a case report
Yuvraj Adhikari, Anupama Marasini, Nawaraj Adhikari, Laxman D. Paneru, Binit Upadhaya Regmi, Manita Raut
Annals of Medicine & Surgery.2023; 85(5): 1940. CrossRef
Hürthle Cell Carcinoma: Single Center Analysis and Considerations for Surgical Management Based on the Recent Literature
Costanza Chiapponi, Milan J.M. Hartmann, Matthias Schmidt, Michael Faust, Christiane J. Bruns, Anne M. Schultheis, Hakan Alakus
Frontiers in Endocrinology.2022;[Epub] CrossRef

Thyroid
Whole-Exome Sequencing in Papillary Microcarcinoma: Potential Early Biomarkers of Lateral Lymph Node Metastasis: Mijin Kim, Chae Hwa Kwon, Min Hee Jang, Jeong Mi Kim, Eun Heui Kim, Yun Kyung Jeon, Sang Soo Kim, Kyung-Un Choi, In Joo Kim, Meeyoung Park, Bo Hyun Kim; Endocrinol Metab. 2021;36(5):1086-1094. Published online October 28, 2021; DOI: https://doi.org/10.3803/EnM.2021.1132

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Background
Early identification of patients with high-risk papillary thyroid microcarcinoma (PTMC) that is likely to progress has become a critical challenge. We aimed to identify somatic mutations associated with lateral neck lymph node (LN) metastasis (N1b) in patients with PTMC.
Methods
Whole-exome sequencing (WES) of 14 PTMCs with no LN metastasis (N0) and 13 N1b PTMCs was performed using primary tumors and matched normal thyroid tissues.
Results
The mutational burden was comparable in N0 and N1b tumors, as the median number of mutations was 23 (range, 12 to 46) in N0 and 24 (range, 12 to 50) in N1b PTMC (P=0.918). The most frequent mutations were detected in PGS1, SLC4A8, DAAM2, and HELZ in N1b PTMCs alone, and the K158Q mutation in PGS1 (four patients, Fisher’s exact test P=0.041) was significantly enriched in N1b PTMCs. Based on pathway analysis, somatic mutations belonging to the receptor tyrosine kinase-RAS and NOTCH pathways were most frequently affected in N1b PTMCs. We identified four mutations that are predicted to be pathogenic in four genes based on Clinvar and Combined Annotation-Dependent Depletion score: BRAF, USH2A, CFTR, and PHIP. A missense mutation in CFTR and a nonsense mutation in PHIP were detected in N1b PTMCs only, although in one case each. BRAF mutation was detected in both N0 and N1b PTMCs.
Conclusion
This first comprehensive WES analysis of the mutational landscape of N0 and N1b PTMCs identified pathogenic genes that affect biological functions associated with the aggressive phenotype of PTMC.

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Bobby White, Pawel Swietach
Pflügers Archiv - European Journal of Physiology.2024; 476(4): 673. CrossRef
Comprehensive Long-Read Sequencing Analysis Discloses the Transcriptome Features of Papillary Thyroid Microcarcinoma
Yanqiang Wang, Binbin Zou, Yanyan Zhang, Jin Zhang, Shujing Li, Bo Yu, Zhekun An, Lei Li, Siqian Cui, Yutong Zhang, Jiali Yao, Xiuzhi Shi, Jing Liu
The Journal of Clinical Endocrinology & Metabolism.2024; 109(5): 1263. CrossRef
Feasibility of whole‐exome sequencing in fine‐needle aspiration specimens of papillary thyroid microcarcinoma for the identification of novel gene mutations
Liyuan Ma, Luying Gao, Ya Hu, Xiaoyi Li, Chunhao Liu, Jiang Ji, Xinlong Shi, Aonan Pan, Yuang An, Nengwen Luo, Yu Xia, Yuxin Jiang
Clinical Genetics.2024; 105(5): 567. CrossRef
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Frontiers in Genetics.2023;[Epub] CrossRef

Review Articles

Thyroid
The Concept of Economic Evaluation and Its Application in Thyroid Cancer Research: Kyungsik Kim, Mijin Kim, Woojin Lim, Bo Hyun Kim, Sue K. Park; Endocrinol Metab. 2021;36(4):725-736. Published online August 27, 2021; DOI: https://doi.org/10.3803/EnM.2021.1164

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Economic evaluation is a type of comparative analysis between interventions in terms of both their resource use and health outcomes. Due to the good prognosis of thyroid cancer (TC), the socioeconomic burden of TC patients post-diagnosis is increasing. Therefore, economic evaluation studies focusing on TC are recommended. This study aimed to describe the concept and methods of economic evaluation and reviewed previous TC studies. Several previous studies compared the costs of interventions or evaluated recurrence, complications, or quality of life as measures of their effectiveness. Regarding costs, most studies focused on direct costs and applied hypothetical models. Cost-minimization analysis should be distinguished from simple cost analysis. Furthermore, due to the universality of the term “cost-effectiveness analysis” (CEA), several studies have not distinguished CEA from cost-utility analysis; this point needs to be considered in future research. Cost-benefit analyses have not been conducted in previous TC research. Since TC has a high survival rate and good prognosis, the need for economic evaluations has recently been pointed out. Therefore, correct concepts and methods are needed to obtain clear economic evaluation results. On this basis, it will be possible to provide appropriate guidelines for TC treatment and management in the future.

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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
Role of Prehabilitation and Rehabilitation on Functional Recovery and Quality of Life in Thyroid Cancer Patients: A Comprehensive Review
Lorenzo Lippi, Alessio Turco, Stefano Moalli, Marco Gallo, Claudio Curci, Antonio Maconi, Alessandro de Sire, Marco Invernizzi
Cancers.2023; 15(18): 4502. CrossRef
Sex-specific Associations between Body Mass Index and Thyroid Cancer Incidence among Korean Adults
Kyoung-Nam Kim, Kyungsik Kim, Sangjun Lee, Sue K. Park
Cancer Epidemiology, Biomarkers & Prevention.2023; 32(9): 1227. CrossRef
Active Surveillance Versus Immediate Surgery for Low-Risk Papillary Thyroid Microcarcinoma Patients in South Korea: A Cost-Minimization Analysis from the MAeSTro Study
Kyungsik Kim, June Young Choi, Su-jin Kim, Eun Kyung Lee, Young Ki Lee, Jun Sun Ryu, Kyu Eun Lee, Jae Hoon Moon, Young Joo Park, Sun Wook Cho, Sue K. Park
Thyroid.2022; 32(6): 648. CrossRef
A Systematic Review of Economic Evaluation of Thyroid Cancer
Mijin Kim, Woojin Lim, Kyungsik Kim, Ja Seong Bae, Byung Joo Lee, Bon Seok Koo, Eun Kyung Lee, Eu Jeong Ku, June Young Choi, Bo Hyun Kim, Sue K. Park
International Journal of Thyroidology.2022; 15(2): 74. CrossRef

Thyroid
Current Guidelines for Management of Medullary Thyroid Carcinoma: Mijin Kim, Bo Hyun Kim; Endocrinol Metab. 2021;36(3):514-524. Published online June 22, 2021; DOI: https://doi.org/10.3803/EnM.2021.1082

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Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor originating from the parafollicular cells. The diagnostic and therapeutic strategies for the condition are different from those used for well-differentiated thyroid cancer. Since the 2015 American Thyroid Association guidelines for the diagnosis and treatment of MTC, the latest, including the National Comprehensive Cancer Network and European Association for Medical Oncology guidelines have been updated to reflect several recent advances in the management of MTC. Advances in molecular diagnosis and postoperative risk stratification systems have led to individualized treatment and follow-up strategies. Multi-kinase inhibitors, such as vandetanib and cabozantinib, can prolong disease progression-free survival with favorable adverse effects. In addition, potent selective rearranged during transfection (RET) inhibitors (selpercatinib and pralsetinib) have shown a promising efficacy in recent clinical trials. This review summarizes the management of MTC in recent guidelines focused on sporadic MTC.

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Original Articles

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.

Citations

Citations to this article as recorded by

Nomogram predicts cervical lymph node metastasis of pathological subtypes of papillary thyroid carcinoma
Ziyu Luo, Wenhan Li, Binliang Huo, Jianhui Li
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Serum thyroglobulin testing after thyroid lobectomy in patients with 1–4 cm papillary thyroid carcinoma
Ahreum Jang, Meihua Jin, Chae A Kim, Min Ji Jeon, Yu-Mi Lee, Tae-Yon Sung, Tae Yong Kim, Won Bae Kim, Young Kee Shong, Won Gu Kim
Endocrine.2023; 81(2): 290. CrossRef
Do Histologically Aggressive Subtypes of Papillary Thyroid Microcarcinoma have Worse Clinical Outcome than Non-Aggressive Papillary Thyroid Microcarcinoma Subtypes? A Multicenter Cohort Study
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Xing Zhao, Yijia Zhang, Pengyu Hao, Mingzhen Zhao, Xingbin Shen
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A Retrospective Cohort Study with Validation of Predictors of Differentiated Thyroid Cancer Outcomes
Ayanthi Wijewardene, Anthony J. Gill, Matti Gild, Diana L. Learoyd, Anthony Robert Glover, Mark Sywak, Stan Sidhu, Paul Roach, Geoffrey Schembri, Jeremy Hoang, Bruce Robinson, Lyndal Tacon, Roderick Clifton-Bligh
Thyroid.2022;[Epub] CrossRef
Clinicopathological Implications of the BRAFV600E Mutation in Papillary Thyroid Carcinoma of Ukrainian Patients Exposed to the Chernobyl Radiation in Childhood: A Study for 30 Years After the Accident
Liudmyla Zurnadzhy, Tetiana Bogdanova, Tatiana I. Rogounovitch, Masahiro Ito, Mykola Tronko, Shunichi Yamashita, Norisato Mitsutake, Michael Bolgov, Serhii Chernyshov, Sergii Masiuk, Vladimir A. Saenko
Frontiers in Medicine.2022;[Epub] CrossRef

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.

Citations

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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
Clinical impact of coexistent chronic lymphocytic thyroiditis on central lymph node metastasis in low- to intermediate-risk papillary thyroid carcinoma: The MASTER study
Da Beom Heo, Ho-Ryun Won, Kyung Tae, Yea Eun Kang, Eonju Jeon, Yong Bae Ji, Jae Won Chang, June Young Choi, Hyeong Won Yu, Eu Jeong Ku, Eun Kyung Lee, Mijin Kim, Jun-Ho Choe, Bon Seok Koo
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Prognostic Implications of Maintaining the Target Thyroid-Stimulating Hormone Status Based on the 2015 American Thyroid Association Guidelines in Patients with Low-Risk Papillary Thyroid Carcinoma after Lobectomy: A 5-Year Landmark Analysis
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ASO Author Reflections: Active Surveillance may be Possible in Patients with T1b Papillary Thyroid Carcinoma Over 55 Years of Age Without High-Risk Features on Preoperative Examinations
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Clinical Study
Protocol for a Korean Multicenter Prospective Cohort Study of Active Surveillance or Surgery (KoMPASS) in Papillary Thyroid Microcarcinoma: Min Ji Jeon, Yea Eun Kang, Jae Hoon Moon, Dong Jun Lim, Chang Yoon Lee, Yong Sang Lee, Sun Wook Kim, Min-Hee Kim, Bo Hyun Kim, Ho-Cheol Kang, Minho Shong, Sun Wook Cho, Won Bae Kim; Endocrinol Metab. 2021;36(2):359-364. Published online March 23, 2021; DOI: https://doi.org/10.3803/EnM.2020.890; Correction in: Endocrinol Metab 2022;37(1):181

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Background
A Korean Multicenter Prospective cohort study of Active Surveillance or Surgery (KoMPASS) for papillary thyroid microcarcinomas (PTMCs) has been initiated. The aim is to compare clinical outcomes between active surveillance (AS) and an immediate lobectomy for low-risk PTMCs. We here outline the detailed protocol for this study.
Methods
Adult patients with a cytopathologically confirmed PTMC sized 6.0 to 10.0 mm by ultrasound (US) will be included. Patients will be excluded if they have a suspicious extra-thyroidal extension or metastasis of a PTMC or multiple thyroid nodules or other thyroid diseases which require a total thyroidectomy. Printed material describing the prognosis of PTMCs, and the pros and cons of each management option, will be provided to eligible patients to select their preferred intervention. For the AS group, thyroid US, thyroid function, and quality of life (QoL) parameters will be monitored every 6 months during the first year, and then annually thereafter. Disease progression will be defined as a ≥3 mm increase in maximal diameter of a PTMC, or the development of new thyroid cancers or metastases. If progression is detected, patients should undergo appropriate surgery. For the lobectomy group, a lobectomy with prophylactic central neck dissection will be done within 6 months. After initial surgery, thyroid US, thyroid function, serum thyroglobulin (Tg), anti-Tg antibody, and QoL parameters will be monitored every 6 months during the first year and annually thereafter. Disease progression will be defined in these cases as the development of new thyroid cancers or metastases.
Conclusion
KoMPASS findings will help to confirm the role of AS, and develop individualized management strategies, for low-risk PTMCs.

Citations

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Jee Hee Yoon, Wonsuk Choi, Ji Yong Park, A Ram Hong, Hee Kyung Kim, Ho-Cheol Kang
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Active Surveillance for Low-Risk Papillary Thyroid Carcinoma as an Acceptable Management Option with Additional Benefits: A Comprehensive Systematic Review
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Journal of Korean Medical Science.2023;[Epub] CrossRef
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Clinical Study
Clinical Implication of World Health Organization Classification in Patients with Follicular Thyroid Carcinoma in South Korea: A Multicenter Cohort Study: Meihua Jin, Eun Sook Kim, Bo Hyun Kim, Hee Kyung Kim, Hyon-Seung Yi, Min Ji Jeon, Tae Yong Kim, Ho-Cheol Kang, Won Bae Kim, Young Kee Shong, Mijin Kim, Won Gu Kim; Endocrinol Metab. 2020;35(3):618-627. Published online September 22, 2020; DOI: https://doi.org/10.3803/EnM.2020.742

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Background
The study aimed to compare the prognostic value of the 4th edition of World Health Organization classification (WHO-2017) with the previous WHO classification (WHO-2004) for follicular thyroid carcinoma (FTC).
Methods
This multicenter retrospective cohort study included 318 patients with FTC from five tertiary centers who underwent thyroid surgery between 1996 and 2009. We evaluated the prognosis of patients with minimally invasive (MI), encapsulated angioinvasive (EA), and widely invasive (WI) FTC according to WHO-2017. Further, we evaluated the proportion of variation explained (PVE) and Harrell’s C-index to compare the predictability of disease-free survival (DFS) and disease-specific survival (DSS).
Results
In total, 227, 58, and 33 patients had MI-, EA-, and WI-FTC, respectively. During a median follow-up of 10.6 years, 46 (14.5%) patients had disease recurrence and 20 (6.3%) patients died from FTC. The 10-year DFS rates of patients with MI-, EA-, and WI-FTC were 91.1%, 78.2%, and 54.9%, respectively (P<0.001, PVE=7.1%, C-index=0.649). The corresponding 10-year DSS rates were 95.9%, 93.5%, and 73.5%, respectively (P<0.001, PVE=2.6%, C-index=0.624). The PVE and C-index values were higher using WHO-2017 than using WHO-2004 for the prediction of DFS, but not for DSS. In multivariate analysis, older age (P=0.02), gross extrathyroidal extension (ETE) (P=0.003), and distant metastasis (P<0.001) were independent risk factors for DSS.
Conclusion
WHO-2017 improves the predictability of DFS, but not DSS, in patients with FTC. Distant metastasis, gross ETE and older age (≥55 years) were independent risk factors for DSS.

Citations

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Association of Ultrasonography Features of Follicular Thyroid Carcinoma With Tumor Invasiveness and Prognosis Based on WHO Classification and TERT Promoter Mutation
Myoung Kyoung Kim, Hyunju Park, Young Lyun Oh, Jung Hee Shin, Tae Hyuk Kim, Soo Yeon Hahn
Korean Journal of Radiology.2024; 25(1): 103. CrossRef
Clinical Outcomes and Implications of Radioactive Iodine Therapy on Cancer-specific Survival in WHO Classification of FTC
Genpeng Li, Ziyang Ye, Tao Wei, Jingqiang Zhu, Zhihui Li, Jianyong Lei
The Journal of Clinical Endocrinology & Metabolism.2024; 109(9): 2294. CrossRef
Radioiodine whole body scan pitfalls in differentiated thyroid cancer
Cristina Basso, Alessandra Colapinto, Valentina Vicennati, Alessandra Gambineri, Carla Pelusi, Guido Di Dalmazi, Elisa Lodi Rizzini, Elena Tabacchi, Arber Golemi, Letizia Calderoni, Stefano Fanti, Uberto Pagotto, Andrea Repaci
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Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Part I. Initial Management of Differentiated Thyroid Cancers - Chapter 5. Evaluation of Recurrence Risk Postoperatively and Initial Risk Stratification in Different
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David Leong, Anthony J. Gill, John Turchini, Michael Waller, Roderick Clifton‐Bligh, Anthony Glover, Mark Sywak, Stan Sidhu
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Ting Zhang, Liang He, Zhihong Wang, Wenwu Dong, Wei Sun, Ping Zhang, Hao Zhang
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Molecular classification of follicular thyroid carcinoma based on TERT promoter mutations
Hyunju Park, Hyeong Chan Shin, Heera Yang, Jung Heo, Chang-Seok Ki, Hye Seung Kim, Jung-Han Kim, Soo Yeon Hahn, Yun Jae Chung, Sun Wook Kim, Jae Hoon Chung, Young Lyun Oh, Tae Hyuk Kim
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Johan O Paulsson, Nima Rafati, Sebastian DiLorenzo, Yi Chen, Felix Haglund, Jan Zedenius, C Christofer Juhlin
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Clinicopathological Characteristics and Disease-Free Survival in Patients with Hürthle Cell Carcinoma: A Multicenter Cohort Study in South Korea
Meihua Jin, Eun Sook Kim, Bo Hyun Kim, Hee Kyung Kim, Yea Eun Kang, Min Ji Jeon, Tae Yong Kim, Ho-Cheol Kang, Won Bae Kim, Young Kee Shong, Mijin Kim, Won Gu Kim
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Clinical Study
Vandetanib for the Management of Advanced Medullary Thyroid Cancer: A Real-World Multicenter Experience: Mijin Kim, Jee Hee Yoon, Jonghwa Ahn, Min Ji Jeon, Hee Kyung Kim, Dong Jun Lim, Ho-Cheol Kang, In Joo Kim, Young Kee Shong, Tae Yong Kim, Bo Hyun Kim; Endocrinol Metab. 2020;35(3):587-594. Published online September 22, 2020; DOI: https://doi.org/10.3803/EnM.2020.687

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Background
Vandetanib is the most widely used tyrosine kinase inhibitor for the treatment of patients with advanced medullary thyroid cancer (MTC). However, only limited data regarding its use outside clinical trials are available. We aimed to evaluate the efficacy and safety of vandetanib in patients with advanced MTC in routine clinical practice.
Methods
In this multicenter retrospective study, 12 patients with locally advanced or metastatic MTC treated with vandetanib at four tertiary hospitals were included. The primary outcome was the objective response rate (ORR) based on the Response Evaluation Criteria in Solid Tumors. The progression-free survival (PFS), overall survival (OS), and toxicities were also evaluated.
Results
Eleven patients (92%) had distant metastasis and 10 (83%) had disease progression at enrollment. Partial response was observed in five patients (ORR, 42%) and stable disease lasting ≥24 weeks was reported in an additional five patients (83%). During the median 31.7 months of follow-up, disease progression was seen in five patients (42%); of these, two died due to disease progression. The median PFS was 25.9 months, while the median OS was not reached. All patients experienced adverse events (AEs) which were generally consistent with the known safety profile of vandetanib. Vandetanib was discontinued in two patients due to skin toxicity.
Conclusion
Consistent with the phase III trial, this study confirmed the efficacy of vandetanib for advanced MTC in terms of both ORR and PFS in the real-world setting. Vandetanib was well tolerated in the majority of patients, and there were no fatal AEs.

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Response

Thyroid
Association between Serum Free Thyroxine and Anemia in Euthyroid Adults: A Nationwide Study (Endocrinol Metab 2020;35:106-14, Mijin Kim et al.): Mijin Kim, Bo Hyun Kim; Endocrinol Metab. 2020;35(3):669-670. Published online July 30, 2020; DOI: https://doi.org/10.3803/EnM.2020.306

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