Endocrinology and Metabolism

Review Article

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.

Original Articles

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.

Citations

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Development and validation of a prognostic model for first-line immunotherapy for metastatic esophageal squamous cell carcinoma
Loulu Gao, Jieqiong Peng, Zixuan Hu, Xiangxue Li, Siyi Zhang, Xiaoxuan Li, Ziheng Zhang, Jing Lv, Jialin Song, Wensheng Qiu
International Immunopharmacology.2026; 168: 115813. CrossRef
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
Turning tumor microenvironmental foes to friends: A new opportunity for thyroid cancer therapy and redifferentiation
Liya Zhu, Xiuli Jing, Byeong-Cheol Ahn
Oral Oncology.2025; 168: 107513. CrossRef
Predictive and prognostic role of Neutrophil-to-Lymphocyte ratio in patients with advanced thyroid cancer treated with targeted therapy
Tuerhong Diliyaer, Yueyan Ren, Xuejiao Chen, Xixi Zhu, Tuerxun Yilidana, Jiaye Liu, Gang Chen, Zhihui Li
Endocrine.2025; 90(3): 1380. CrossRef

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

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

Citations

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Thyroid Nodules: Past, Present, and Future
Alan A. Parsa, Hossein Gharib
Endocrine Practice.2025; 31(1): 114. CrossRef
Approach to the Patient With Thyroid Cancer: Selection and Management of Candidates for Lobectomy
Eyal Robenshtok, Gideon Bachar, Amit Ritter
The Journal of Clinical Endocrinology & Metabolism.2025; 110(7): e2327. 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
2025 Korean Thyroid Association Clinical Management Guideline on Active Surveillance for Low-Risk Papillary Thyroid Carcinoma
Eun Kyung Lee, Min Joo Kim, Seung Heon Kang, Bon Seok Koo, Kyungsik Kim, Mijin Kim, Bo Hyun Kim, Ji-hoon Kim, Shin Je Moon, Kyorim Back, Young Shin Song, Jong-hyuk Ahn, Hwa Young Ahn, Ho-Ryun Won, Won Sang Yoo, Min Kyoung Lee, Jeongmin Lee, Ji Ye Lee, Kyo
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Endocrinology and Metabolism Clinics of North America.2025; 54(3): 377. CrossRef
2025 Korean Thyroid Association Clinical Management Guideline on Active Surveillance for Low-Risk Papillary Thyroid Carcinoma
Eun Kyung Lee, Min Joo Kim, Seung Heon Kang, Bon Seok Koo, Kyungsik Kim, Mijin Kim, Bo Hyun Kim, Ji-hoon Kim, 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, Kyon
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Risk factors for lateral neck lymph node metastasis in papillary thyroid ultra micro carcinoma with implications for active surveillance
Hyeung Kyoo Kim, Ho Jung Jeong, Jin Seok Lee, Soo Young Kim, Yong Sang Lee, Hang-Seok Chang
Scientific Reports.2025;[Epub] CrossRef
From screening to follow-up: a review of quality of life and psychological status across the clinical care continuum in patients with differentiated thyroid cancer
Zifeng Kuang, Hao Zhao, Chenjia Zhang, Xiaoyi Li
Frontiers in Psychology.2025;[Epub] CrossRef
It Is Time to Understand the Additional Benefits of Active Surveillance for Low-Risk Papillary Thyroid Carcinoma
Kyeong Jin Kim
Endocrinology and Metabolism.2024; 39(1): 95. CrossRef

Review Article

Thyroid
Evaluation and Management of Bone Health in Patients with Thyroid Diseases: A Position Statement of the Korean Thyroid Association: A Ram Hong, Ho-Cheol Kang; Endocrinol Metab. 2023;38(2):175-189. Published online April 27, 2023; DOI: https://doi.org/10.3803/EnM.2023.1701

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Thyroid hormones play an important physiological role in maintaining adult bone structure and strength. Consequently, thyroid dysfunction is related to skeletal outcomes. Overt hyperthyroidism is an established cause of high bone turnover with accelerated bone loss, leading to osteoporosis and increased fracture risk. Hyperthyroidism induced by thyroid-stimulating hormone-suppressive therapy in patients with differentiated thyroid cancer is a cause of secondary osteoporosis. In contrast, there is a lack of evidence on the negative impact of hypothyroidism on bone health. Considering the clinical updates on the importance of bone health in thyroid dysfunction, the Task Force from the Clinical Practice Guidelines Development Committee of the Korean Thyroid Association recently developed a position statement on the evaluation and management of bone health of patients with thyroid diseases, particularly focused on endogenous hyperthyroidism and thyroid-stimulating hormone-suppressive therapy-associated hyperthyroidism in patients with differentiated thyroid cancer. Herein, we review the Korean Thyroid Association’s position statement on the evaluation and management of bone health associated with thyroid diseases.

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Increased risk of malignancy and osteoporosis in primary Sjögren’s syndrome with thyroid diseases: potential implication from T cells
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Risk of Osteoporotic Fractures among Patients with Thyroid Cancer: A Nationwide Population-Based Cohort Study
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Original Article

Thyroid Thyroid Cancer Screening
A Comprehensive Assessment of the Harms of Fine-Needle Aspiration Biopsy for Thyroid Nodules: A Systematic Review: Ji Yong Park, Wonsuk Choi, A Ram Hong, Jee Hee Yoon, Hee Kyung Kim, Ho-Cheol Kang; Endocrinol Metab. 2023;38(1):104-116. Published online February 27, 2023; DOI: https://doi.org/10.3803/EnM.2023.1669

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Background
There have concerns related with the potential harms of fine-needle aspiration biopsy (FNAB). We aimed to summarize the clinical complications and evaluate the safety of FNAB.
Methods
Studies related with the harms of FNAB were searched on MEDLINE, Embase, Cochrane library, and KoreaMed from 2012 to 2022. Also, studies reviewed in the previous systematic reviews were evaluated. Included clinical complications were postprocedural pain, bleeding events, neurological symptoms, tracheal puncture, infections, post-FNAB thyrotoxicosis, and needle tract implantation of thyroid cancers.
Results
Twenty-three cohort studies were included in this review. Nine studies which were related with FNAB-related pain showed that most of the subjects had no or mild discomfort. The 0% to 6.4% of the patients had hematoma or hemorrhage after FNAB, according to 15 studies. Vasovagal reaction, vocal cord palsy, and tracheal puncture have rarely described in the included studies. Needle tract implantation of thyroid malignancies was described in three studies reporting 0.02% to 0.19% of the incidence rate.
Conclusion
FNAB is considered to be a safe diagnostic procedure with rare complications, which are mainly minor events. Thorough assessement of the patients’ medical condition when deciding to perform FNABs would be advisable to lower potential complications.

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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
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Original Articles

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.

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Andrea Marongiu, Susanna Nuvoli, Andrea De Vito, Antonio Mura, Sonia Vargiu, Angela Spanu, Giuseppe Madeddu
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Hanxing Sun, Hui Tong, Xiaohui Shen, Haoji Gao, Jie Kuang, Xi Chen, Qinyu Li, Weihua Qiu, Zhuoran Liu, Jiqi Yan
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Young Ju Choi, Kyungdo Han, Won Kyoung Cho, Min Ho Jung, Byung-Kyu Suh
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Marco Palella, Francesca Maria Giustolisi, Adriana Modica Fiascaro, Martina Fichera, Antonella Palmieri, Rossella Cannarella, Aldo E. Calogero, Margherita Ferrante, Maria Fiore
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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
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Table of Contents

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Predisposition to and Prognosis of Thyroid Cancer May Not Be Affected by Graves’ Disease, But Some Questions Still Remain
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An unusual case of papillary thyroid carcinoma presenting as Graves’ disease
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An unusual case of papillary thyroid carcinoma presenting as Graves’ disease
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Thyroid
Clinicopathological Characteristics and Disease-Free Survival in Patients with Hürthle Cell Carcinoma: A Multicenter Cohort Study in South Korea: Meihua Jin, Eun Sook Kim, Bo Hyun Kim, Hee Kyung Kim, Yea Eun Kang, Min Ji Jeon, Tae Yong Kim, Ho-Cheol Kang, Won Bae Kim, Young Kee Shong, Mijin Kim, Won Gu Kim; Endocrinol Metab. 2021;36(5):1078-1085. Published online October 28, 2021; DOI: https://doi.org/10.3803/EnM.2021.1151

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

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Giulia Orlando, Giulia Capella, Giulia Vocino Trucco, Elena Vissio, Jasna Metovic, Francesca Maletta, Marco Volante, Mauro Papotti
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Thyroid
Programmed Cell Death-Ligand 1 (PD-L1) gene Single Nucleotide Polymorphism in Graves’ Disease and Hashimoto’s Thyroiditis in Korean Patients: Jee Hee Yoon, Min-ho Shin, Hee Nam Kim, Wonsuk Choi, Ji Yong Park, A Ram Hong, Hee Kyung Kim, Ho-Cheol Kang; Endocrinol Metab. 2021;36(3):599-606. Published online June 2, 2021; DOI: https://doi.org/10.3803/EnM.2021.965

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Background
Programmed cell death-ligand 1 (PD-L1) has an important role in regulating immune reactions by binding to programmed death 1 (PD-1) on immune cells, which could prevent the exacerbation of autoimmune thyroid disease (AITD). The aim of this study was to evaluate the association of PD-L1 polymorphism with AITD, including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT).
Methods
A total of 189 GD patients, 234 HT patients, and 846 healthy age- and sex-matched controls were enrolled in this study. We analyzed PD-L1 single nucleotide polymorphism (SNP) (rs822339) and investigated the associations with clinical disease course and outcome.
Results
Genotype frequency at the PD-L1 marker RS822339 in GD (P=0.219) and HT (P=0.764) patients did not differ from that among healthy controls. In patients with GD, the A/G or G/G genotype group demonstrated higher TBII titer (20.6±20.5 vs. 28.0± 25.8, P=0.044) and longer treatment duration (39.0±40.4 months vs. 62.4±65.0 months, P=0.003) compared to the A/A genotype group. Among patients in whom anti-thyroid peroxidase (TPO) antibody was measured after treatment of GD, post-treatment antiTPO positivity was higher in the A/G or G/G genotype group compared to the A/A genotype group (48.1% vs. 69.9%, P=0.045). Among patients with HT, there was no significant difference of anti-TPO antibody positivity (79.4% vs. 68.6%, P=0.121), anti-thyroglobulin antibody positivity (80.9% vs. 84.7%, P=0.661), or development to overt hypothyroidism (68.0% vs. 71.1%, P=0.632) between the A/A genotype group and the A/G or G/G genotype group.
Conclusion
The genotype frequency of PD-L1 (rs822339) is not different in patients with AITD compared with healthy controls. The intact PD-1/PD-L1 pathway in GD and HT might be important to maintain chronicity of AITD by protecting immune tolerance. However, the PD-L1 SNP could be associated with difficulty in achieving remission in patients with GD, which may be helpful to predict the possibility of longer treatment. Further studies are required to investigate the complex immune tolerance system in patients with AITD.

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Clinical Study
Characteristics of Immune-Related Thyroid Adverse Events in Patients Treated with PD-1/PD-L1 Inhibitors: Jee Hee Yoon, A Ram Hong, Hee Kyung Kim, Ho-Cheol Kang; Endocrinol Metab. 2021;36(2):413-423. Published online April 6, 2021; DOI: https://doi.org/10.3803/EnM.2020.906

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Background
Thyroid immune-related adverse events (IRAEs) have been reported in patients treated with programmed cell death protein-1 (PD-1) and programmed cell death protein-ligand 1 (PD-L1) inhibitors. We investigated the incidence and clinical course of PD-1/PD-L1 inhibitor-induced thyroid IRAEs, and identified predictable clinical risk factors of thyroid IRAEs, in particular, overt hypothyroidism (OH).
Methods
We retrospectively reviewed the medical records of 325 cancer patients receiving PD-1/PD-L1 inhibitor in a tertiary referral center.
Results
A total of 50.5% (164/325) of patients experienced at least one abnormal thyroid function following PD-1/PD-L1 inhibitor. Eighty-four patients (51.2%) of them recovered to normal thyroid function during follow-up. In overall population, 25 patients (7.7%) required thyroid hormone replacement therapy due to PD-1/PD-L1 inhibitor-induced OH. Patients who progressed to OH showed significantly higher baseline thyroid stimulating hormone level and longer duration of PD-1/PD-L1 inhibitor therapy than those without thyroid dysfunction or OH (both P<0.001). Median time interval to the development of OH was 3 months after the therapy. OH was significantly associated with positive anti-thyroid peroxidase antibody at baseline and anti-thyroglobulin antibody during the therapy than those without thyroid dysfunction or OH (P=0.015 and P=0.005, respectively). We observed no patients with OH who were able to stop levothyroxine replacement after the cessation of PD-1/PD-L1 inhibitor therapy.
Conclusion
PD-1/PD-L1 inhibitor-induced thyroid dysfunctions are considerably reversible; however, OH is irreversible requiring levothyroxine replacement even after stopping the therapy. Positive thyroid autoantibodies may predict the progression to OH.

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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.

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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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Min Joo Kim, Hojeong Won, Won Bae Kim, Eun Kyung Lee, Chang Yoon Lee, Sun Wook Cho, Han-Sang Baek, Yong Sang Lee, Yea Eun Kang, Sun Wook Kim, Ho-Cheol Kang, Jeongmin Lee, Mijin Kim, Min Ji Jeon, Jae Hoon Moon
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Ji Ye Lee, Min Kyoung Lee, Hyun Kyung Lim, Chang Yoon Lee, Jin Yong Sung, Jung Hyun Yoon, Soo Yeon Han, Jung Hee Shin, Ji-hoon Kim, So Lyung Jung, Sae Rom Chung, Jung Hwan Baek, Dong Gyu Na
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Standardized Ultrasound Evaluation for Active Surveillance of Low-Risk Thyroid Microcarcinoma in Adults: 2024 Korean Society of Thyroid Radiology Consensus Statement
Ji Ye Lee, Min Kyoung Lee, Hyun Kyung Lim, Chang Yoon Lee, Jin Yong Sung, Jung Hyun Yoon, Soo Yeon Hahn, Jung Hee Shin, Ji-hoon Kim, So Lyung Jung, Sae Rom Chung, Jung Hwan Baek, Dong Gyu Na
Journal of the Korean Society of Radiology.2024; 85(6): 1060. CrossRef
Thyroid‐Stimulating Hormone, Age, and Tumor Size are Risk Factors for Progression During Active Surveillance of Low‐Risk Papillary Thyroid Microcarcinoma in Adults
Yasuhiro Ito, Akira Miyauchi, Makoto Fujishima, Takuya Noda, Tsutomu Sano, Takahiro Sasaki, Taketoshi Kishi, Tomohiko Nakamura
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Mitsuyoshi Hirokawa, Manon Auger, Chan Kwon Jung, Fabiano Mesquita Callegari
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To Screen or Not to Screen?
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Cost-Effectiveness of Active Surveillance Compared to Early Surgery of Small Papillary Thyroid Cancer: A Retrospective Study on a Korean Population
Han-Sang Baek, Jeonghoon Ha, Kwangsoon Kim, Jaseong Bae, Jeong Soo Kim, Sungju Kim, Dong-Jun Lim, Chulmin Kim
Journal of Korean Medical Science.2023;[Epub] CrossRef
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Ik Beom Shin, Do Hoon Koo, Dong Sik Bae
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Thermal Ablation for Papillary Thyroid Microcarcinoma Located in The Isthmus: a Study With 3 Years Of Follow-Up
Lin Zheng, Fang-yi Liu, Jie Yu, Zhi-gang Cheng, Xiao-ling Yu, Xiao-cong Dong, Zhi-yu Han, Ping Liang
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Trends in the Management of Localized Papillary Thyroid Carcinoma in the United States (2000–2018)
Elisa Pasqual, Julie Ann Sosa, Yingxi Chen, Sara J. Schonfeld, Amy Berrington de González, Cari M. Kitahara
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Management of Low-Risk Thyroid Cancers: Is Active Surveillance a Valid Option? A Systematic Review of the Literature
Renato Patrone, Nunzio Velotti, Stefania Masone, Alessandra Conzo, Luigi Flagiello, Chiara Cacciatore, Marco Filardo, Vincenza Granata, Francesco Izzo, Domenico Testa, Stefano Avenia, Alessandro Sanguinetti, Andrea Polistena, Giovanni Conzo
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Cost-Effectiveness Analysis of Active Surveillance Compared to Early Surgery in Small Papillary Thyroid Cancer: A Systemic Review
Han-sang Baek, Chai-ho Jeong, Jeonghoon Ha, Ja-Seong Bae, Jeong-soo Kim, Dong-Jun Lim, Chul-Min Kim
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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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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
Endocrinology and Metabolism.2025; 40(3): 357. CrossRef
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
Eun Kyung Lee, Young Shin Song, Ho-Cheol Kang, Sun Wook Kim, Dong Gyu Na, Shin Je Moon, Dong-Jun Lim, Kyong Yeun Jung, Yun Jae Chung, Chan Kwon Jung, Young Joo Park
International Journal of Thyroidology.2024; 17(1): 68. CrossRef
The Prognostic Impact of Extent of Vascular Invasion in Follicular Thyroid Carcinoma
David Leong, Anthony J. Gill, John Turchini, Michael Waller, Roderick Clifton‐Bligh, Anthony Glover, Mark Sywak, Stan Sidhu
World Journal of Surgery.2023; 47(2): 412. CrossRef
TERT Promoter Mutation as a Prognostic Marker in Encapsulated Angioinvasive and Widely Invasive Follicular Thyroid Carcinomas
Yasuhiro Ito, Takashi Akamizu
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Risk factors for death of follicular thyroid carcinoma: a systematic review and meta-analysis
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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Whole-genome Sequencing of Follicular Thyroid Carcinomas Reveal Recurrent Mutations in MicroRNA Processing Subunit DGCR8
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
Endocrinology and Metabolism.2021; 36(5): 1078. CrossRef

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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Therapeutic Potential of Tyrosine Kinase Inhibitors in Advanced Thyroid Cancer
Prakash Gangadaran, Vidya Sankarapandian, Raksa Arun, Kandasamy Nagarajan ArulJothi, Ramya Lakshmi Rajendran, Ji Min Oh, Athesh Kumaraswamy, Sridharan Gurunagarajan, Byeong-Cheol Ahn
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Neuroendocrine Neoplasms of the Lungs, Thyroid, and Thymus
Barbara Buchalska, Małgorzata Solnik, Karol Maciejewski, Marta Fudalej, Andrzej Deptała, Anna Badowska-Kozakiewicz
Biomedicines.2025; 13(5): 1028. CrossRef
Systemic therapies for medullary thyroid carcinoma: state of the art
Alejandro Román-González, Ines Califano, Marcio Concepción-Zavaleta, Fabian Pitoia, Sarimar Agosto Salgado
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Comprehensive Assessment of Multikinase Inhibitor Therapy Outcomes in RAIR-(P)DTC and MTC at a Tertiary Referral Center
Yara Maria Machlah, Tim Brandenburg, Philipp Muchalla, Vera Tiedje, Sarah Theurer, Manuel Weber, Frank Weber, Henning Dralle, Harald Lahner, Dagmar Führer
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Petar Brlek, Vedrana Škaro, Nenad Hrvatin, Luka Bulić, Ana Petrović, Petar Projić, Martina Smolić, Parth Shah, Dragan Primorac
Cancers.2025; 17(21): 3500. CrossRef
Synthesis of 4-styrylquinazolines enabled by a hypervalent iodine-promoted oxidative amination cascade
Lipeng Long, Ziyi Yu, Ziwen Huang, Min Ye, Wenjun Luo, Xunjin Jiang, Zhengwang Chen, Zhong-Xia Wang
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Diego Fernando Rodríguez, Kelly Johanna Lipez, Elena Stashenko, Iván Díaz, Justo Cobo, Alirio Palma
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Marilda Mormando, Rosa Lauretta, Giulia Puliani, Marta Bianchini, Maria Elena Spoltore, Marialuisa Appetecchia
Biomedicines.2024; 12(12): 2923. CrossRef
Metastatic medullary thyroid carcinoma (MTC): disease course, treatment modalities and factors predisposing for drug resistance
Katerina Saltiki, George Simeakis, Olga Karapanou, Stavroula A. Paschou, Maria Alevizaki
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Initial Experiences of Selective RET Inhibitor Selpercatinib in Adults with Metastatic Differentiated Thyroid Carcinoma and Medullary Thyroid Carcinoma: Real-World Case Series in Korea
Han-Sang Baek, Jeonghoon Ha, Seunggyun Ha, Ja Seong Bae, Chan Kwon Jung, Dong-Jun Lim
Current Oncology.2023; 30(3): 3020. CrossRef
Molecular Basis and Natural History of Medullary Thyroid Cancer: It is (Almost) All in the RET
Nicolas Sahakian, Frédéric Castinetti, Pauline Romanet
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Antonio Matrone, Carla Gambale, Alessandro Prete, Rossella Elisei
Frontiers in Endocrinology.2022;[Epub] CrossRef
Targeted therapy and drug resistance in thyroid cancer
Yujie Zhang, Zhichao Xing, Tianyou Liu, Minghai Tang, Li Mi, Jingqiang Zhu, Wenshuang Wu, Tao Wei
European Journal of Medicinal Chemistry.2022; 238: 114500. CrossRef
Daily Management of Patients on Multikinase Inhibitors’ Treatment
Carla Colombo, Simone De Leo, Matteo Trevisan, Noemi Giancola, Anna Scaltrito, Laura Fugazzola
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Cătălina Ionescu, Bogdan Oprea, Georgeta Ciobanu, Milena Georgescu, Ramona Bică, Garofiţa-Olivia Mateescu, Fidan Huseynova, Veronique Barragan-Montero
Medicina.2022; 58(7): 903. CrossRef
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Current Guidelines for Management of Medullary Thyroid Carcinoma
Mijin Kim, Bo Hyun Kim
Endocrinology and Metabolism.2021; 36(3): 514. CrossRef
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Jolanta Krajewska, Aleksandra Kukulska, Malgorzata Oczko-Wojciechowska, Barbara Jarzab
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Functional evaluation of vandetanib metabolism by CYP3A4 variants and potential drug interactions in vitro
Mingming Han, Xiaodan Zhang, Zhize Ye, Jing Wang, Jianchang Qian, Guoxin Hu, Jianping Cai
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Nephrotoxicity in advanced thyroid cancer treated with tyrosine kinase inhibitors: An update
Alice Nervo, Francesca Retta, Alberto Ragni, Alessandro Piovesan, Alberto Mella, Luigi Biancone, Marco Manganaro, Marco Gallo, Emanuela Arvat
Critical Reviews in Oncology/Hematology.2021; 168: 103533. CrossRef

Clinical Study
Modification of the Tumor-Node-Metastasis Staging System for Differentiated Thyroid Carcinoma by Considering Extra-Thyroidal Extension and Lateral Cervical Lymph Node Metastasis: Mijin Kim, Won Gu Kim, Min Ji Jeon, Hee Kyung Kim, Hyon-Seung Yi, Eun Sook Kim, Bo Hyun Kim, Won Bae Kim, Young Kee Shong, Ho-Cheol Kang, Tae Yong Kim; Endocrinol Metab. 2020;35(1):149-156. Published online March 19, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.1.149

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Background

Concerns have arisen about the classification of extra-thyroidal extension (ETE) and lateral cervical lymph node metastasis (N1b) in the 8th edition of the tumor-node-metastasis staging system (TNM-8). This study evaluated the prognostic validity of a modified-TNM staging system, focusing on ETE and N1b, in differentiated thyroid carcinoma (DTC) patients.

Methods

This multicenter retrospective cohort study included 4,878 DTC patients from five tertiary hospitals. In the modified-TNM, T3b in TNM-8 was down-staged to T2, and stage II was subdivided into stages IIA and IIB. Older patients with N1b were reclassified as stage IIB.

Results

The modified-TNM resulted in staging migration in 540 patients (11%) classified as stage II according to the TNM-8, with 75 (14%), 381 (71%), and 84 patients (16%) classified as stages I, IIA, and IIB, respectively. The 10-year disease-specific survival (DSS) rates in patients classified as stages I, II, III, and IV by TNM-8 were 99.8%, 95.9%, 81.0%, and 41.6%, respectively. The DSS rates of patients classified as stages I, IIA, IIB, III, and IV according to the modified-TNM were 99.8%, 96.4%, 93.3%, 81.0%, and 41.6%, respectively. DSS curves between stages on TNM-8 (P<0.001) and modified-TNM (P<0.001) differed significantly, but the modified-TNM discriminated better than TNM-8. The proportions of variation explained values of TNM-8 and modified-TNM were 6.3% and 6.5%, respectively.

Conclusion

Modification of the TNM staging system focusing on ETE and N1b could improve the prediction of DSS in patients with DTC. Further researches are needed to validate the prognostic accuracy of this modified-TNM staging system.

Citations

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Clinicopathological features of differentiated thyroid carcinoma as predictors of the effects of radioactive iodine therapy
Wen Liu, Beibei Jiang, Jingli Xue, Ruijing Liu, Yuqing Wei, Peifeng Li
Annals of Diagnostic Pathology.2024; 69: 152243. CrossRef
Prognostic significance of T3b in papillary thyroid carcinoma: Appropriateness of classifying T3bN0M0 in patients aged 55 years or older into stage II
Yasuhiro Ito, Akira Miyauchi, Makoto Kawakami, Minoru Kihara, Akihiro Miya
World Journal of Surgery.2024; 48(9): 2132. CrossRef
Thyroid Collision Tumors: The Presence of the Medullary Thyroid Carcinoma Component Negatively Influences the Prognosis
Ion Negura, Victor Ianole, Mihai Danciu, Cristina Preda, Diana Gabriela Iosep, Radu Dănilă, Alexandru Grigorovici, Delia Gabriela Ciobanu Apostol
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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
Prognostic Impact of Microscopic Extra-Thyroidal Extension (mETE) on Disease Free Survival in Patients with Papillary Thyroid Carcinoma (PTC)
Nadia Bouzehouane, Pascal Roy, Myriam Decaussin-Petrucci, Mireille Bertholon-Grégoire, Chantal Bully, Agnès Perrin, Helene Lasolle, Jean-Christophe Lifante, Françoise Borson-Chazot, Claire Bournaud
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Impacts of the American Joint Committee on Cancer (AJCC) 8th edition tumor, node, metastasis (TNM) staging system on outcomes of differentiated thyroid cancer in Thai patients
Yotsapon Thewjitcharoen, Waralee Chatchomchuan, Krittadhee Karndumri, Sriurai Porramatikul, Sirinate Krittiyawong, Ekgaluck Wanothayaroj, Siriwan Butadej, Soontaree Nakasatien, Veekij Veerasomboonsin, Auchai Kanchanapituk, Rajata Rajatanavin, Thep Himatho
Heliyon.2021; 7(3): e06624. CrossRef

Thyroid
Prognosis of Differentiated Thyroid Carcinoma with Initial Distant Metastasis: A Multicenter Study in Korea: Hosu Kim, Hye In Kim, Sun Wook Kim, Jaehoon Jung, Min Ji Jeon, Won Gu Kim, Tae Yong Kim, Hee Kyung Kim, Ho-Cheol Kang, Ji Min Han, Yoon Young Cho, Tae Hyuk Kim, Jae Hoon Chung; Endocrinol Metab. 2018;33(2):287-295. Published online June 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.2.287

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Background

Most patients with differentiated thyroid cancer (DTC) have a favorable prognosis. However, patients with DTC and initial distant metastasis have not been commonly found, and their clinical characteristics have seldom been reported. In this study, we analyzed the clinical features and prognosis of patients with DTC and initial distant metastasis in Korea.

Methods

We retrospectively reviewed the clinical data of 242 patients with DTC and initial distant metastasis treated from 1994 to 2013, collected from five tertiary hospitals in Korea.

Results

The patients' median age was 51 years, and 65% were women. They were followed for a median of 7 years. Lung was the most common site of distant metastasis: only lung 149 patients (62%), only bone 49 (20%), other single site one (pleura), and combined sites 43 (40 were lung and bone, two were bone and other site, and one was lung and other site). At the time of diagnosis, 50 patients (21%) had non-radioactive iodine (RAI) avidity. Five-year disease-specific survival (DSS) was 85% and 10-year DSS was 68%, which were better than those in previous studies. After multivariate analysis, old age, male sex, metastatic site, and histologic type (follicular type) were significant factors for poor prognosis. However, negative RAI avidity status was not a significant prognostic factor after adjusting for other variables.

Conclusion

The prognosis of Korean patients with DTC and initial distant metastasis was better than in previous studies. Old age, male sex, metastasis site, and histologic type were significant prognostic factors.

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Ji Min Han, Ji Cheol Bae, Hye In Kim, Sam Kwon, Min Ji Jeon, Won Gu Kim, Tae Yong Kim, Young Kee Shong, Won Bae Kim
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Clinical Study
Disease-Specific Mortality of Differentiated Thyroid Cancer Patients in Korea: A Multicenter Cohort Study: Min Ji Jeon, Won Gu Kim, Tae Hyuk Kim, Hee Kyung Kim, Bo Hyun Kim, Hyon-Seung Yi, Eun Sook Kim, Hosu Kim, Young Nam Kim, Eun Heui Kim, Tae Yong Kim, Sun Wook Kim, Ho-Cheol Kang, Jae Hoon Chung, Young Kee Shong, Won Bae Kim; Endocrinol Metab. 2017;32(4):434-441. Published online November 22, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.4.434

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Background

Little is known regarding disease-specific mortality of differentiated thyroid cancer (DTC) patients and its risk factors in Korea.

Methods

We retrospectively reviewed a large multi-center cohort of thyroid cancer from six Korean hospitals and included 8,058 DTC patients who underwent initial surgery between 1996 and 2005.

Results

Mean age of patients at diagnosis was 46.2±12.3 years; 87% were females. Most patients had papillary thyroid cancer (PTC; 97%) and underwent total thyroidectomy (85%). Mean size of the primary tumor was 1.6±1.0 cm. Approximately 40% of patients had cervical lymph node (LN) metastases and 1.3% had synchronous distant metastases. During 11.3 years of follow-up, 150 disease-specific mortalities (1.9%) occurred; the 10-year disease-specific survival (DSS) rate was 98%. According to the year of diagnosis, the number of disease-specific mortality was not different. However, the rate of disease-specific mortality decreased during the study period (from 7.7% to 0.7%). Older age (≥45 years) at diagnosis, male, follicular thyroid cancer (FTC) versus PTC, larger tumor size (>2 cm), presence of extrathyroidal extension (ETE), lateral cervical LN metastasis, distant metastasis and tumor node metastasis (TNM) stage were independent risk factors of disease-specific mortality of DTC patients.

Conclusion

The rate of disease-specific mortality of Korean DTC patients was 1.9%; the 10-year DSS rate was 98% during 1996 to 2005. Older age at diagnosis, male, FTC, larger tumor size, presence of ETE, lateral cervical LN metastasis, distant metastasis, and TNM stages were significant risk factors of disease-specific mortality of Korean DTC patients.

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Clinical Study
The Recovery of Hypothalamic-Pituitary-Adrenal Axis Is Rapid in Subclinical Cushing Syndrome: Hee Kyung Kim, Jee Hee Yoon, Yun Ah Jeong, Ho-Cheol Kang; Endocrinol Metab. 2016;31(4):592-597. Published online December 20, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.4.592

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Background

In subclinical Cushing syndrome (SC), it is assumed that glucocorticoid production is insufficient to cause a clinically recognizable syndrome. Differences in hormonal levels or recovery time of the hypothalamic-pituitary-adrenocortical (HPA) axis after adrenalectomy between patients with overt Cushing syndrome (OC) and SC remain unknown.

Methods

Thirty-six patients (10 with OC and 26 with SC) with adrenal Cushing syndrome who underwent adrenalectomy from 2004 to 2014 were reviewed retrospectively. Patients were treated with glucocorticoid after adrenalectomy and were reevaluated every 1 to 6 months using a rapid adrenocorticotropic hormone (ACTH) stimulation test.

Results

Levels of basal 24-hour urine free cortisol (UFC), serum cortisol after an overnight dexamethasone suppression test (DST), and serum cortisol and 24-hour UFC after low-dose DST and high-dose DST were all significantly lower in patients with SC compared with OC. Basal ACTH levels showed significantly higher in patients with SC compared with OC. The probability of recovering adrenal function during follow-up differed significantly between patients with OC and SC (P=0.001), with significant correlations with the degree of preoperative cortisol excess. Patients with OC required a longer duration of glucocorticoid replacement to recover a normal ACTH stimulation test compared with patients with SC (median 17.0 months vs. 4.0 months, P<0.001).

Conclusion

The HPA axis recovery time after adrenalectomy in patients with SC is rapid and is dependent on the degree of cortisol excess. More precise definition of SC is necessary to achieve a better management of patients and to avoid the risk of under- or over-treatment of SC patients.

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Yui Kubo, Masakatsu Sone, Takuyuki Katabami, Shoichiro Izawa, Takamasa Ichijo, Mika Tsuiki, Shintaro Okamura, Takanobu Yoshimoto, Michio Otsuki, Yoshiyu Takeda, Tomoko Suzuki, Mitsuhide Naruse, Akiyo Tanabe
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Hypothalamic–pituitary–adrenal axis recovery after treatment of Cushing's syndrome
Annemarie Balasko, Karin Zibar Tomsic, Darko Kastelan, Tina Dusek
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Early assessment of postoperative adrenal function is necessary after adrenalectomy for mild autonomous cortisol secretion
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Martha K P Huayllas, Brian C Netzel, Ravinder J Singh, Claudio E Kater
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Clinical Study
Characteristics of Korean Patients with Antithyroid Drug-Induced Agranulocytosis: A Multicenter Study in Korea: Hee Kyung Kim, Jee Hee Yoon, Min Ji Jeon, Tae Yong Kim, Young Kee Shong, Min Jin Lee, Bo Hyun Kim, In Joo Kim, Ji Young Joung, Sun Wook Kim, Jae Hoon Chung, Ho-Cheol Kang; Endocrinol Metab. 2015;30(4):475-480. Published online December 31, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.4.475

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Background

Antithyroid drugs (ATDs) can lead to the development of agranulocytosis, which is the most serious adverse effect. Characteristics of ATD-induced agranulocytosis (AIA) have seldom been reported due to the rarity. In this study, we characterized the clinical features for AIA in Korean patients.

Methods

We retrospectively reviewed data from patients with AIA diagnosed between 1997 and 2014 at four tertiary hospitals. Agranulocytosis was defined as an absolute neutrophil count (ANC) below 500/mm³.

Results

The mean age of the patients (11 males, 43 females) was 38.2±14.9 years. Forty-eight patients (88.9%) with AIA had fever and sore throat on initial presentation, 20.4% of patients developed AIA during the second course of treatment, and 75.9% of patients suffered AIA within 3 months after initiation of ATD. The patients taking methimazole (n=39) showed lower levels of ANC and more frequent use of granulocyte-macrophage colony-stimulating factor than propylthiouracil (n=15) users. The median duration of agranulocytosis was 5.5 days (range, 1 to 20). No differences were observed between the long (≥6 days) and short recovery time (≤5 days) groups in terms of age, gender, ATDs, duration of ATDs, or initial ANC levels. Four patients (7.4%) who were taking ATDs for less than 2 months died of sepsis on the first or second day of hospitalization.

Conclusion

The majority of AIA incidents occur in the early treatment period. Considering the high fatality rate of AIA, an early aggressive therapeutic approach is critical and patients should be well informed regarding the warning symptoms of the disease.

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Jung Jun Lee, Dong Young Kim, Jeon Yeob Jang
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Association of HLA-B∗38:02 with Antithyroid Drug-Induced Agranulocytosis in Kinh Vietnamese Patients
Mai Phuong Thao, Pham Vo Anh Tuan, Le Gia Hoang Linh, Lam Van Hoang, Phan Huu Hen, Le Tuyet Hoa, Hoang Anh Vu, Do Duc Minh
International Journal of Endocrinology.2018; 2018: 1. CrossRef
Severe Gingival Ulceration and Necrosis Caused by an Antithyroid Drug: One Case Report and Proposed Clinical Approach
Ying‐Ying Chang, Chih‐Wen Tseng, Kuo Yuan
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Emphasis on the early diagnosis of antithyroid drug-induced agranulocytosis: retrospective analysis over 16 years at one Chinese center
Y. He, J. Li, J. Zheng, Z. Khan, W. Qiang, F. Gao, Y. Zhao, B. Shi
Journal of Endocrinological Investigation.2017; 40(7): 733. CrossRef
Association of HLA-B and HLA-DRB1 polymorphisms with antithyroid drug-induced agranulocytosis in a Han population from northern China
Yayi He, Jie Zheng, Qian Zhang, Peng Hou, Feng Zhu, Jian Yang, Wenhao Li, Pu Chen, Shu Liu, Bao Zhang, Bingyin Shi
Scientific Reports.2017;[Epub] CrossRef
Use of granulocyte colony‐stimulating factor in the treatment of methimazole‐induced agranulocytosis: a case report
Asha Birmingham, Carissa Mancuso, Craig Williams
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2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis
Douglas S. Ross, Henry B. Burch, David S. Cooper, M. Carol Greenlee, Peter Laurberg, Ana Luiza Maia, Scott A. Rivkees, Mary Samuels, Julie Ann Sosa, Marius N. Stan, Martin A. Walter
Thyroid.2016; 26(10): 1343. CrossRef

Case Reports

Thyroid
Hypoparathyroidism and Subclinical Hypothyroidism with Secondary Hemochromatosis: Hyung Ki Jeong, Joon Hwan An, Hyoung Sang Kim, Eun Ae Cho, Min Gui Han, Jung Sik Moon, Hee Kyung Kim, Ho-Cheol Kang; Endocrinol Metab. 2014;29(1):91-95. Published online March 14, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.1.91

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Hemochromatosis is an inherited genetic disorder of iron metabolism which can also occur as a secondary result of iron-overload. It leads to organ damage such as cardiomyopathy, liver cirrhosis, hypogonadism, and diabetes. This paper discusses a case of secondary hemochromatosis associated with repeated transfusions, presenting as asymptomatic hypoparathyroidism and subclinical hypothyroidism with multiple organ involvement. The 29-year-old female, who had severe aplastic anemia, received multiple transfusions totaling approximately 1,400 units of red blood cells over 15 years. During her routine laboratory examination, hypocalcemia was detected with decreased intact parathyroid hormone and increased thyroid stimulating hormone. Serum ferritin, iron, and total iron binding capacity had increased to 27,583.03 ng/mL, 291 µg/dL, and 389 µg/dL, respectively. She had unusually bronze skin and computed tomography revealed iron deposition in the thyroid, liver, and heart. Multiorgan involvement as seen in this case is rare in hemochromatosis associated with secondary transfusions. To the best of the author's knowledge, this is the first case report in Korea of hypoparathyroidism and subclinical hypothyroidism due to iron deposition in the parathyroid and thyroid gland.

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Differential effects of Fe2+ and Fe3+ on osteoblasts and the effects of 1,25(OH)2D3, deferiprone and extracellular calcium on osteoblast viability under iron-overloaded conditions
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J. Warland, B. Skelly, C. Knudsen, M. Herrtage
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Articles in 'Endocrinology and Metabolism' in 2014
Won-Young Lee
Endocrinology and Metabolism.2015; 30(1): 47. CrossRef

Thyroid
Benign Teratoma of the Thyroid Gland: Chan Young Oak, Hee Kyung Kim, Tae Mi Yoon, Sang Chul Lim, Hyun Bum Park, Hyung Chul Park, Min Gui Han, Ho-Cheol Kang; Endocrinol Metab. 2013;28(2):144-148. Published online June 18, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.2.144

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Although pathology reports of thyroid tissue in ovarian teratomas are abundant, benign teratomas of the thyroid are extremely rare in adolescents and adults. Therefore, their clinical characteristics are still not well characterized. We report a case of a 54-year-old woman with a growing mass in her neck. Left lobectomy of the thyroid revealed it to be a benign thyroid teratoma composed of tissues from all three germ layers. Preoperative evaluations included thyroid ultrasonography (US), ultrasound-guided fine needle aspiration cytology (FNAC), and computed tomography (CT) of the neck. A 4.7-cm, well defined, predominantly hypoechoic mass intermingled with hyperechoic internal lesions, was observed in the inferior portion of the left thyroid lobe with substernal extension on US. The posterior extent of the nodule was not visualized due to deep attenuation of the echo. US-guided FNAC failed to reveal any thyroid follicular cells, but suggested a benign cystic tumor. Neck CT hinted at the diagnosis of teratoma because the mass contained large amounts of fat, and the margin was well defined. Extrathyroidal extension and cervical lymphadenopathy were not seen. She underwent left thyroid lobectomy, and histologic examination confirmed benign thyroid teratoma. To the best of our knowledge, this is the first case report of benign thyroid teratoma in Korea.

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Yuan Yuan, Long Qin, Mengwei Shi, Yingli Wang, Yang Gao, Qingwei Chen, Qingyu Ji
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Meera R Laxman, Laura L Hayes, Santino S Cervantes, Tamarah Westmoreland
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Constantinos Nastos, Anna Paspala, Mathew Stamelos, Ioanna Mavroeidi, Konstantinos Proikas, Georgia Thomopoulou, Amanda Psyrri, Emmanuil Pikoulis
Molecular and Clinical Oncology.2021;[Epub] CrossRef
A Case of Teratoma of Thyroid Gland in Adolescence
Yu-Chang Lee, Su-Jin Jeong, Sol-Jae Lee, Chong-Hwa Kim, Yong-Hoon Lee, Jung-Eun Lee, Hye-Ji Seo
International Journal of Thyroidology.2017; 10(1): 61. CrossRef
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Case Report: Severe acute respiratory distress by tracheal obstruction due to a congenital thyroid teratoma.
Jose Colleti Junior, Uenis Tannuri, Felipe Monti Lora, Eliana Carla Armelin Benites, Walter Koga, Janete Honda Imamura, Patricia Rute Moutinho, Werther Brunow de Carvalho
F1000Research.2015; 4: 159. CrossRef
Case Report: Severe acute respiratory distress by tracheal obstruction due to a congenital thyroid teratoma: a case report and literature review.
Jose Colleti Junior, Uenis Tannuri, Felipe Monti Lora, Eliana Carla Armelin Benites, Walter Koga, Janete Honda Imamura, Patricia Rute Moutinho, Werther Brunow de Carvalho
F1000Research.2015; 4: 159. CrossRef
Case Report: Severe acute respiratory distress by tracheal obstruction due to a congenital thyroid teratoma.
Jose Colleti Junior, Uenis Tannuri, Felipe Monti Lora, Eliana Carla Armelin Benites, Walter Koga, Janete Honda Imamura, Patricia Rute Moutinho, Werther Brunow de Carvalho
F1000Research.2015; 4: 159. CrossRef
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Thyroid
Riedel Thyroiditis in a Patient with Graves Disease: Doo Young Lee, Jung Sik Moon, Ga-Eon Kim, Hee Kyung Kim, Ho-Cheol Kang; Endocrinol Metab. 2013;28(2):138-143. Published online June 18, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.2.138

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Riedel's thyroiditis is a rare form of infiltrative and inflammatory disease of the thyroid gland and can be associated with systemic fibrotic processes, Hashimoto thyroiditis and Graves disease. Riedel thyroiditis in combination with Graves disease however, is very rare. A 57-year-old woman with a past medical history significant for Graves disease diagnosed 30 years ago presented with an enlarging neck mass and voice changes. Due to suspicion of malignancy, thyroidectomy was performed. Histopathologic examination revealed Riedel thyroiditis. To our knowledge, the association of Riedel thyroiditis with Graves disease has not yet been reported in our country. Here we report a patient with Riedel thyroiditis evolved from antecedent Graves disease.

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