Endocrinology and Metabolism

Original Article

Thyroid
High TRAb Titer at Diagnosis Predicts Persistent Positivity and Relapse in Graves’ Disease after Prolonged Antithyroid Therapy: Zimiao Chen, Jinglu Xu, Wenrui Kang, Yang Zhang, Rujun Chen, Xiaohua Gong; Endocrinol Metab. 2025;40(6):950-960. Published online September 16, 2025; DOI: https://doi.org/10.3803/EnM.2025.2405

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Background
The association between high thyrotropin receptor antibody (TRAb) titers at diagnosis and long-term outcomes following prolonged antithyroid drug (ATD) therapy in Graves’ disease (GD) remains unclear. This study examined TRAb dynamics and outcomes in high-titer patients receiving prolonged ATD.
Methods
In this retrospective cohort (2018–2021), 1,148 of 3,052 newly diagnosed GD patients met inclusion criteria (≥18-month ATD course, TRAb negativity before withdrawal, and ≥12-month follow-up). Initial TRAb levels were defined as low-titer (<5.25 IU/L, 3×upper normal limit [UNL]), intermediate-titer (5.25–10.5 IU/L), and high-titer (>10.5 IU/L, 6×UNL). Outcomes included TRAb dynamics, treatment duration, and relapse.
Results
High-titer patients required longer therapy (50 months vs. 30 months vs. 22 months, P<0.001) and slower thyroid-stimulating hormone normalization (6 months vs. 4 months vs. 2 months, both P<0.001). TRAb negativity at 24/48 months occurred in 91.85%/99.26% (low-titer), 52.38%/75.24% (intermediate-titer), and 12.70%/52.68% (high-titer) (P<0.001). High-titer patients showed fluctuant (46.20%) or smoldering (28.89%) trends. Remission rates declined with higher TRAb titer (60.45% vs. 42.70% vs. 30.47%, P<0.001). High-titer patients showed increased risk of persistent TRAb positivity (2.17-fold; 95% confidence interval [CI], 1.55 to 3.05) and relapse (1.66-fold; 95% CI, 1.45 to 3.22). Thresholds of 10.90 IU/L and 16.01 IU/L predicted positivity and relapse, respectively. Definitive therapy post-relapse was more common in high-titer patients (38.29% vs. 16.98% in low-titer, P<0.001).
Conclusion
High TRAb titers strongly predict persistent TRAb positivity and relapse after ATD withdrawal. Cut-off at 10.90 and 16.01 IU/L may guide prognosis and treatment.

Citations

Citations to this article as recorded by

Peripartum Management of Refractory Graves’ Thyrotoxicosis
Sonam Tshering, Ashutosh Kapoor, Sophie Buckley, Fareeha Rizvi
Cureus.2026;[Epub] CrossRef

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
Microvascular Ultrasonography Vascularity Index as a Rapid and Simplified Assessment Tool for Differentiating Graves’ Disease from Destructive Thyroiditis and Managing Thyrotoxicosis: Han-Sang Baek, Chaiho Jeong, Jeonghoon Ha, Dong-Jun Lim; Endocrinol Metab. 2025;40(3):394-404. Published online February 25, 2025; DOI: https://doi.org/10.3803/EnM.2024.2206

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Background
Thyrotoxicosis presents significant diagnostic challenges in distinguishing Graves’ disease (GD) from destruction-induced thyrotoxicosis (DT) using ultrasound imaging. We evaluated a new technology, microvascular ultrasonography (MVUS) to effectively differentiate between GD and DT, and observe the MVUS changes during follow-up.
Methods
A total of 264 consecutive patients were prospectively enrolled into two cohorts from August 2022 to March 2024 at one tertiary referral hospital: cohort 1 comprised patients initially presenting with thyrotoxicosis (n=185; 98 with GD and 87 with DT). Cohort 2 included patients either with GD considering antithyroid drug discontinuation or with DT in the follow-up phase after treatment (n=77). Ultrasound imaging was conducted using the MVUS technique, and the vascularity index (MVUS-VI) was automatically calculated as the percentage ratio of color pixels to total grayscale pixels within a specified region of interest.
Results
Diagnostic accuracy highlighted MVUS-VI as the most accurate diagnostic tool, achieving a sensitivity of 79.6%, specificity of 84.3%, with an area under the curve of 0.856 (95% confidence interval, 0.800 to 0.911). Presence of thyroid peroxidase antibody or thyroglobulin antibody affected MVUS-VI’s performance, requiring a higher cut-off value for specificity in this subgroup. Follow-up in cohort 2 (n=77) demonstrated significant normalization in thyroid function and reductions in MVUS-VI from an initial 32.6%±23.4% to 20.8%±13.5% at follow-up (P<0.001).
Conclusion
MVUS-VI provides a rapid, non-invasive diagnostic alternative to traditional methods in differentiating GD from DT, thus aiding in the management of patients with thyrotoxicosis.

Citations

Citations to this article as recorded by

Update on newer ultrasound systems to study the microvasculature
Orlando Catalano, Antonio Pio Masciotra
La radiologia medica.2025; 130(8): 1283. CrossRef
Diagnostic Approach and Therapeutic Strategies for Ambiguous Thyrotoxicosis
Mijin Kim
The Korean Journal of Medicine.2025; 100(5): 241. CrossRef

Thyroid Big Data Articles (National Health Insurance Service Database)
Unveiling Risk Factors for Treatment Failure in Patients with Graves’ Disease: A Nationwide Cohort Study in Korea: Jung A Kim, Kyeong Jin Kim, Jimi Choi, Kyoung Jin Kim, Eyun Song, Ji Hee Yu, Nam Hoon Kim, Hye Jin Yoo, Ji A Seo, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Sin Gon Kim; Endocrinol Metab. 2025;40(1):125-134. Published online January 13, 2025; DOI: https://doi.org/10.3803/EnM.2024.2093

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Background
Antithyroid drug (ATD) treatment is the preferred initial treatment for Graves’ disease (GD) in South Korea, despite higher treatment failure rates than radioactive iodine (RAI) therapy or thyroidectomy. This study aimed to evaluate the incidence of treatment failure associated with the primary modalities for GD treatment in real-world practice.
Methods
We included 452,001 patients diagnosed with GD between 2004 and 2020 from the Korean National Health Insurance Service-National Health Information Database. Treatment failure was defined as switching from ATD, RAI, or thyroidectomy treatments, and for ATD specifically, inability to discontinue medication for over 2 years.
Results
Mean age was 46.2 years, with females constituting 70.8%. Initial treatments for GD included ATDs (98.0%), thyroidectomy (1.3%), and RAI (0.7%), with a noted increment in ATD application from 96.2% in 2004 to 98.8% in 2020. During a median follow- up of 8.5 years, the treatment failure rates were 58.5% for ATDs, 21.3% for RAI, and 2.1% for thyroidectomy. Multivariate analysis indicated that the hazard ratio for treatment failure with ATD was 2.81 times higher than RAI. RAI treatments ≥10 mCi had 37% lower failure rates than doses <10 mCi.
Conclusion
ATDs are the most commonly used for GD in South Korea, followed by thyroidectomy and RAI. Although the risk of treatment failure for ATD is higher than that of RAI therapy, initial RAI treatment in South Korea is relatively limited compared to that in Western countries. Further studies are required to evaluate the cause of low initial RAI treatment rates in South Korea.

Citations

Citations to this article as recorded by

Treatment of Graves’ Disease: Faster Remission or Longer but Safe, That Is the Question
Chan-Hee Jung
Endocrinology and Metabolism.2025; 40(1): 70. CrossRef
Process to radioactive iodine treatment for Graves’ hyperthyroidism: condemned or absolved?
Luigi Bartalena, Daniela Gallo, George J. Kahaly, Eliana Piantanida, Maria Laura Tanda
Journal of Endocrinological Investigation.2025; 48(9): 1927. CrossRef

Review Article

Thyroid
Long-Term Antithyroid Drug Therapy in Smoldering or Fluctuating-Type Graves’ Hyperthyroidism with Potassium Iodide: Ken Okamura; Endocrinol Metab. 2024;39(6):827-838. Published online October 16, 2024; DOI: https://doi.org/10.3803/EnM.2024.2079

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Graves’ hyperthyroidism is characterized by stimulation of the thyroid gland by thyroid-stimulating hormone receptor antibodies (TRAbs). Antithyroid drug (ATD) continuation is recommended as long as the thyroid gland is stimulated. Goiter size, thyroidal ¹²³I uptake, serum thyroglobulin level, and TRAb positivity are reliable markers of thyroid stimulation. Attention must also be paid to the responsiveness of the thyroid gland due to the high prevalence of painless thyroiditis and spontaneous hypothyroidism during treatment. TRAbs disappeared at <5 years entering remission in 36.6% of patients (smooth-type), while re-elevation of TRAb activity occurred in 37.7% (fluctuating-type) and remained positive for >5 years in 21.1% (smoldering-type). Seven percent of patients remained positive for TRAbs for >30 years, requiring life-long ATD treatment. Remission occurred after median 6.8 years (interquartile range, 4.0 to 10.9) of ATD treatment in 55% of patients. However, late relapse may occur after stressful events (dormant type). In apparently intractable Graves’ disease (GD) with a large goiter (>40 g), ¹³¹I therapy should be considered. For initial and long-term ATD treatment, we must choose effective, safe, and economical drugs such as 100 mg potassium iodide (KI), although KI sensitivity varies in patients with GD. Thionamide, which has notorious side effects, is added only during the KI-resistant period.

Citations

Citations to this article as recorded by

Therapeutic effectiveness of iodine-rich herbs in treating Graves’ hyperthyroidism: a retrospective cohort study from a single center
Yiwen Lai, Mengfei Yang, Jing Li, Di Gan, Qingyang Liu, Yingna Wang, Tianshu Gao
Frontiers in Endocrinology.2025;[Epub] CrossRef
High TRAb Titer at Diagnosis Predicts Persistent Positivity and Relapse in Graves’ Disease after Prolonged Antithyroid Therapy
Zimiao Chen, Jinglu Xu, Wenrui Kang, Yang Zhang, Rujun Chen, Xiaohua Gong
Endocrinology and Metabolism.2025; 40(6): 950. CrossRef

Original Article

Thyroid
Comparison of Thyroid Size-Specific Radioiodine Dose and New Modified Dose Calculation in the Treatment of Graves’ Disease: Alisara Wongsuttilert, Ruchirek Thamcharoen, Yoswanich Maiprasert, Sathapakorn Siriwong; Endocrinol Metab. 2024;39(5):758-766. Published online October 14, 2024; DOI: https://doi.org/10.3803/EnM.2024.1950

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Abstract PDF Supplementary Material PubReader ePub: Background
Previous studies of fixed-dose radioiodine therapy (RIT) for Graves’ disease (GD) have utilized a variety of techniques and reported differing success rates. This study sought to compare the efficacy of RIT using two fixed-dose protocols and to estimate the optimal radioiodine (RAI) activity for the treatment of GD.
Methods
This retrospective trial enrolled 658 patients with GD who received RIT between January 2014 and December 2021. Participants were divided into two groups: protocol 1, which utilized a thyroid size-specific RAI dose, and protocol 2, which employed a modified dose calculation approach. The primary outcome assessed was the presence of euthyroidism or hypothyroidism at the 6-month follow-up. The success rates of RIT were compared between the two protocols.
Results
The RIT success rate was marginally lower for protocol 2 than for protocol 1 (63.6% vs. 67.2%); however, the risk of treatment failure did not differ considerably between the groups (relative risk, 1.1089; 95% confidence interval, 0.8937 to 1.3758; P=0.3477). The median RAI activity associated with protocol 2 was lower than that for protocol 1 (10.7 mCi vs. 15.0 mCi, P=0.0079), and the frequency of hypothyroidism was significantly lower in the protocol 2 group (39.0% vs. 48.9%, P=0.0117).
Conclusion
The success rate of the modified dose calculation protocol was comparable to that of the thyroid size-specific RAI dose protocol. The former approach reduced RAI activity and the incidence of hypothyroidism following RIT without compromising the success rate.

Brief Report

Thyroid
Treatment Patterns and Preferences for Graves’ Disease in Korea: Insights from a Nationwide Cohort Study: Kyeong Jin Kim, Jimi Choi, Soo Myoung Shin, Jung A Kim, Kyoung Jin Kim, Sin Gon Kim; Endocrinol Metab. 2024;39(4):659-663. Published online August 5, 2024; DOI: https://doi.org/10.3803/EnM.2024.2042

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Treatment patterns and preferences for patients with Graves’ disease (GD) vary across countries. In this study, we assessed the initial therapies and subsequent treatment modalities employed for GD in real-world clinical practice in Korea. We analyzed 452,001 patients with GD from 2004 to 2020, obtained from the Korean National Health Insurance Service database. Initial treatments included antithyroid drug (ATD) therapy (98% of cases), thyroidectomy (1.3%), and radioactive iodine (RAI) therapy (0.7%). The rates of initial treatment failure were 58.5% for ATDs, 21.3% for RAI, and 2.1% for thyroidectomy. Even among cases of ATD treatment failure or recurrence, the rates of RAI therapy remained low. Regarding initial treatment, the 5-year remission rate was 46.8% among patients administered ATDs versus 91.0% among recipients of RAI therapy; at 10 years, these rates were 59.2% and 94.0%, respectively. Our findings highlight a marked disparity in the use of RAI therapy in Korea compared to Western countries. Further research is required to understand the reasons for these differences in treatment patterns.

Citations

Citations to this article as recorded by

2025 Korean Thyroid Association Management Guidelines for Radioactive Iodine Therapy in Patients with Hyperthyroidism
Kyeong Jin Kim, Eyun Song, Mijin Kim, Hyemi Kwon, Eu Jeong Ku, Hyun Woo Kwon, Jee Hee Yoon, Eun Kyung Lee, Won Woo Lee, Young Joo Park, Dong-Jun Lim, Sun Wook Kim, Ho-Cheol Kang, Jae Hoon Chung, Tae Yong Kim, Sin Gon Kim, Dong Gyu Na, Jee Soo Kim
International Journal of Thyroidology.2025; 18(1): 65. CrossRef
2025 Korean Thyroid Association Management Guidelines for Radioactive Iodine Therapy in Patients with Hyperthyroidism
Kyeong Jin Kim, Eyun Song, Mijin Kim, Hyemi Kwon, Eu Jeong Ku, Hyun Woo Kwon, Jee Hee Yoon, Eun Kyung Lee, Won Woo Lee, Young Joo Park, Dong-Jun Lim, Sun Wook Kim, Ho-Cheol Kang, Jae Hoon Chung, Tae Yong Kim, Sin Gon Kim, Dong Gyu Na, Jee Soo Kim
Endocrinology and Metabolism.2025; 40(3): 342. CrossRef

Original Articles

Thyroid
The Early Changes in Thyroid-Stimulating Immunoglobulin Bioassay over Anti-Thyroid Drug Treatment Could Predict Prognosis of Graves’ Disease: Jin Yu, Han-Sang Baek, Chaiho Jeong, Kwanhoon Jo, Jeongmin Lee, Jeonghoon Ha, Min Hee Kim, Jungmin Lee, Dong-Jun Lim; Endocrinol Metab. 2023;38(3):338-346. Published online June 9, 2023; DOI: https://doi.org/10.3803/EnM.2023.1664

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Background
To determine whether baseline thyroid-stimulating immunoglobulin (TSI) bioassay or its early response upon treatment with an anti-thyroid drug (ATD) can predict prognosis of Graves’ disease (GD) in real-world practice.
Methods
This retrospective study enrolled GD patients who had previous ATD treatment with TSI bioassay checked at baseline and at follow-up from April 2010 to November 2019 in one referral hospital. The study population were divided into two groups: patients who experienced relapse or continued ATD (relapse/persistence), and patients who experienced no relapse after ATD discontinuation (remission). The slope and area under the curve at 1st year (AUC_1yr) of thyroid-stimulating hormone receptor antibodies including TSI bioassay and thyrotropin-binding inhibitory immunoglobulin (TBII) were calculated as differences between baseline and second values divided by time duration (year).
Results
Among enrolled 156 study subjects, 74 (47.4%) had relapse/persistence. Baseline TSI bioassay values did not show significant differences between the two groups. However, the relapse/persistence group showed less decremental TSI bioassay in response to ATD than the remission group (–84.7 [TSI slope, –198.2 to 8.2] vs. –120.1 [TSI slope, –204.4 to –45.9], P=0.026), whereas the TBII slope was not significantly different between the two groups. The relapse/persistence group showed higher AUC_1yr of TSI bioassay and TBII in the 1st year during ATD treatment than the remission group (AUC_1yr for TSI bioassay, P=0.0125; AUC_1yr for TBII, P=0.001).
Conclusion
Early changes in TSI bioassay can better predict prognosis of GD than TBII. Measurement of TSI bioassay at beginning and follow-up could help predict GD prognosis.

Citations

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A Predictive Model for Graves’ Disease Recurrence After Antithyroid Drug Therapy: A Retrospective Multicenter Cohort Study
Omar El Kawkgi, David Toro-Tobon, Freddy J.K. Toloza, Sebastian Vallejo, Cristian Soto Jacome, Ivan N. Ayala, Bryan A. Vallejo, Camila Wenczenovicz, Olivia Tzeng, Horace J. Spencer, Jeff D. Thostenson, Dingfeng Li, Jacob Kohlenberg, Eddy Lincango, Sneha M
Endocrine Practice.2025; 31(4): 455. CrossRef
Microvascular Ultrasonography Vascularity Index as a Rapid and Simplified Assessment Tool for Differentiating Graves’ Disease from Destructive Thyroiditis and Managing Thyrotoxicosis
Han-Sang Baek, Chaiho Jeong, Jeonghoon Ha, Dong-Jun Lim
Endocrinology and Metabolism.2025; 40(3): 394. CrossRef
High TRAb Titer at Diagnosis Predicts Persistent Positivity and Relapse in Graves’ Disease after Prolonged Antithyroid Therapy
Zimiao Chen, Jinglu Xu, Wenrui Kang, Yang Zhang, Rujun Chen, Xiaohua Gong
Endocrinology and Metabolism.2025; 40(6): 950. CrossRef
Enhanced predictive validity of integrative models for refractory hyperthyroidism considering baseline and early therapy characteristics: a prospective cohort study
Xinpan Wang, Tiantian Li, Yue Li, Qiuyi Wang, Yun Cai, Zhixiao Wang, Yun Shi, Tao Yang, Xuqin Zheng
Journal of Translational Medicine.2024;[Epub] CrossRef
Long-term Effect of Thyrotropin-binding Inhibitor Immunoglobulin on Atrial Fibrillation in Euthyroid Patients
Jung-Chi Hsu, Kang-Chih Fan, Ting-Chuan Wang, Shu-Lin Chuang, Ying-Ting Chao, Ting-Tse Lin, Kuan-Chih Huang, Lian-Yu Lin, Lung-Chun Lin
Endocrine Practice.2024; 30(6): 537. CrossRef
Dynamic Risk Model for the Medical Treatment of Graves’ Hyperthyroidism according to Treatment Duration
Meihua Jin, Chae A Kim, Min Ji Jeon, Won Bae Kim, Tae Yong Kim, Won Gu Kim
Endocrinology and Metabolism.2024; 39(4): 579. CrossRef

Thyroid
Metabolite Changes during the Transition from Hyperthyroidism to Euthyroidism in Patients with Graves’ Disease: Ho Yeop Lee, Byeong Chang Sim, Ha Thi Nga, Ji Sun Moon, Jingwen Tian, Nguyen Thi Linh, Sang Hyeon Ju, Dong Wook Choi, Daiki Setoyama, Hyon-Seung Yi; Endocrinol Metab. 2022;37(6):891-900. Published online December 26, 2022; DOI: https://doi.org/10.3803/EnM.2022.1590

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Background
An excess of thyroid hormones in Graves’ disease (GD) has profound effects on systemic energy metabolism that are currently partially understood. In this study, we aimed to provide a comprehensive understanding of the metabolite changes that occur when patients with GD transition from hyperthyroidism to euthyroidism with methimazole treatment.
Methods
Eighteen patients (mean age, 38.6±14.7 years; 66.7% female) with newly diagnosed or relapsed GD attending the endocrinology outpatient clinics in a single institution were recruited between January 2019 and July 2020. All subjects were treated with methimazole to achieve euthyroidism. We explored metabolomics by performing liquid chromatography-mass spectrometry analysis of plasma samples of these patients and then performed multivariate statistical analysis of the metabolomics data.
Results
Two hundred metabolites were measured before and after 12 weeks of methimazole treatment in patients with GD. The levels of 61 metabolites, including palmitic acid (C16:0) and oleic acid (C18:1), were elevated in methimazole-naïve patients with GD, and these levels were decreased by methimazole treatment. The levels of another 15 metabolites, including glycine and creatinine, were increased after recovery of euthyroidism upon methimazole treatment in patients with GD. Pathway analysis of metabolomics data showed that hyperthyroidism was closely related to aminoacyl-transfer ribonucleic acid biosynthesis and branched-chain amino acid biosynthesis pathways.
Conclusion
In this study, significant variations of plasma metabolomic patterns that occur during the transition from hyperthyroidism to euthyroidism were detected in patients with GD via untargeted metabolomics analysis.

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Genetic associations of plasma metabolites with immune cells in hyperthyroidism revealed by Mendelian randomization and GWAS-sc-eQTLs xQTLbiolinks analysis
Yutong Li, Xingyu Song, Yuyang Huang, Sifan Zhou, Linkun Zhong
Scientific Reports.2025;[Epub] CrossRef
Butyrate Ameliorates Graves’ Orbitopathy Through Regulating Orbital Fibroblast Phenotypes and Gut Microbiota
Pingbo Ouyang, Jia Qi, Boding Tong, Yunping Li, Jiamin Cao, Lujue Wang, Tongxin Niu, Xin Qi
Investigative Ophthalmology & Visual Science.2025; 66(3): 5. CrossRef
Serum metabolome analysis in hyperthyroid cats before and after radioactive iodine therapy
Molly A. Bechtold, Yimei Lin, Meredith L. Miller, Jennifer M. Prieto, Carol E. Frederick, Lucinda L. Bennett, Mark E. Peterson, Kenneth W. Simpson, John P. Loftus, Anu Sayal
PLOS ONE.2024; 19(6): e0305271. CrossRef
Evaluation of the Dysregulation of Cholesterol and Glucose Levels in Graves' Disease Using Clinical Data Analysis
Zainab Razaq Kareem, Fatin Fadhel Al-Kazazz, Ahmed Mahdi Rheima, Ameer Radhi Sultan
Reports of Biochemistry and Molecular Biology.2024; 13(2): 159. CrossRef
Associations of serum keratin 1 with thyroid function and immunity in Graves’ disease
Chao-Wen Cheng, Wen-Fang Fang, Jiunn-Diann Lin, Appuwawadu Mestri Nipun Lakshitha de Silva
PLOS ONE.2023; 18(11): e0289345. CrossRef

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

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

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

Thyroid
Immunoglobulin G4-Related Thyroid Disease: A Single-Center Experience and Literature Review: Meihua Jin, Bictdeun Kim, Ahreum Jang, Min Ji Jeon, Young Jun Choi, Yu-Mi Lee, Dong Eun Song, Won Gu Kim; Endocrinol Metab. 2022;37(2):312-322. Published online April 25, 2022; DOI: https://doi.org/10.3803/EnM.2021.1318

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Background
Immunoglobulin G4 (IgG4)-related disease is an entity that can involve the thyroid gland. The spectrum of IgG4-related thyroid disease (IgG4-RTD) includes Hashimoto thyroiditis (HT) and its fibrotic variant, Riedel thyroiditis, as well as Graves’ disease. The early diagnosis of IgG4-RTD is important because it is a medically treatable disease, and a delay in the diagnosis might result in unnecessary surgery. We present a case series of IgG4-RTD with a review of the literature.
Methods
We retrospectively reviewed the clinical presentation and the radiological and pathological findings of patients diagnosed with IgG4-RTD between 2017 and 2021 at a tertiary medical center in Korea. We also conducted a literature review of IgG4-RTD.
Results
Five patients were diagnosed with IgG4-RTD during the study period. The patients’ age ranged from 31 to 76 years, and three patients were men. Most patients visited the clinic for a neck mass, and hypoechogenic nodular lesions were observed on neck ultrasonography. Three patients had IgG4 HT, and two patients had IgG4 Riedel thyroiditis. All patients developed hypothyroidism that necessitated L-thyroxine replacement. The diagnosis of IgG4-RTD was confirmed after a pathological examination of the surgical specimen in the first two cases. However, the early diagnosis was possible after a core needle biopsy in three clinically suspected patients.
Conclusion
The diagnosis of IgG4-RTD requires clinical suspicion combined with serology and histological analyses using IgG4 immunostaining. The early diagnosis of IgG4-RTD is difficult; thus, biopsy with IgG4 immunostaining and serum IgG4 measurements will help diagnose patients suspected of having IgG4-RTD.

Citations

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IgG4-Related Disease: Current and Future Insights into Pathological Diagnosis
Marlon Arias-Intriago, Tamar Gomolin, Flor Jaramillo, Adriana C. Cruz-Enríquez, Angie L. Lara-Arteaga, Andrea Tello-De-la-Torre, Esteban Ortiz-Prado, Juan S. Izquierdo-Condoy
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Thyroid
Usefulness of Real-Time Quantitative Microvascular Ultrasonography for Differentiation of Graves’ Disease from Destructive Thyroiditis in Thyrotoxic Patients: Han-Sang Baek, Ji-Yeon Park, Chai-Ho Jeong, Jeonghoon Ha, Moo Il Kang, Dong-Jun Lim; Endocrinol Metab. 2022;37(2):323-332. Published online April 13, 2022; DOI: https://doi.org/10.3803/EnM.2022.1413

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Background
Microvascular ultrasonography (MVUS) is a third-generation Doppler technique that was developed to increase sensitivity compared to conventional Doppler. The purpose of this study was to compare MVUS with conventional color Doppler (CD) and power Doppler (PD) imaging to distinguish Graves’ disease (GD) from destructive thyroiditis (DT).
Methods
This prospective study included 101 subjects (46 GDs, 47 DTs, and eight normal controls) from October 2020 to November 2021. All ultrasonography examinations were performed using microvascular flow technology (MV-Flow). The CD, PD, and MVUS images were semi-quantitatively graded according to blood flow patterns. On the MVUS images, vascularity indices (VIs), which were the ratio (%) of color pixels in the total grayscale pixels in a defined region of interest, were obtained automatically. Receiver operating characteristic curve analysis was performed to verify the diagnostic performance of MVUS. The interclass correlation coefficient and Cohen’s kappa analysis were used to analyze the reliability of MVUS (ClinicalTrials.gov:NCT04879173).
Results
The area under the curve (AUC) for CD, PD, MVUS, and MVUS-VI was 0.822, 0.844, 0.808, and 0.852 respectively. The optimal cutoff value of the MVUS-VI was 24.95% for distinguishing GD and DT with 87% sensitivity and 80.9% specificity. We found a significant positive correlation of MVUS-VI with thyrotropin receptor antibody (r=0.554) and with thyroid stimulating immunoglobulin bioassay (r=0.841). MVUS showed high intra- and inter-observer reliability from various statistical method.
Conclusion
In a real time and quantitative manner, MVUS-VI could be helpful to differentiate GD from thyroiditis in thyrotoxic patients, with less inter-observer variability.

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Microvascular Ultrasonography Vascularity Index as a Rapid and Simplified Assessment Tool for Differentiating Graves’ Disease from Destructive Thyroiditis and Managing Thyrotoxicosis
Han-Sang Baek, Chaiho Jeong, Jeonghoon Ha, Dong-Jun Lim
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Association of autoimmune thyroid disease with type 1 diabetes mellitus and its ultrasonic diagnosis and management
Jin Wang, Ke Wan, Xin Chang, Rui-Feng Mao
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Deep Learning Analysis With Gray Scale and Doppler Ultrasonography Images to Differentiate Graves’ Disease
Han-Sang Baek, Jinyoung Kim, Chaiho Jeong, Jeongmin Lee, Jeonghoon Ha, Kwanhoon Jo, Min-Hee Kim, Tae Seo Sohn, Ihn Suk Lee, Jong Min Lee, Dong-Jun Lim
The Journal of Clinical Endocrinology & Metabolism.2024; 109(11): 2872. CrossRef
Evaluation of normal and abnormal fetal renal microvascular flow characteristics of three-dimensional MV-flow imaging
Caixin Huang, Lihe Zhang, Yuting Jiang, Qiao Zheng, Ting Lei, Liu Du, Hongning Xie
Early Human Development.2024; 199: 106149. CrossRef
The Early Changes in Thyroid-Stimulating Immunoglobulin Bioassay over Anti-Thyroid Drug Treatment Could Predict Prognosis of Graves’ Disease
Jin Yu, Han-Sang Baek, Chaiho Jeong, Kwanhoon Jo, Jeongmin Lee, Jeonghoon Ha, Min Hee Kim, Jungmin Lee, Dong-Jun Lim
Endocrinology and Metabolism.2023; 38(3): 338. CrossRef
Duplex Hemodynamic Parameters of Both Superior and Inferior Thyroid Arteries in Evaluation of Thyroid Hyperfunction Disorders
Maha Assem Hussein, Alaa Abdel Hamid, Rasha M Abdel Samie, Elshaymaa Hussein, Shereen Sadik Elsawy
International Journal of General Medicine.2022; Volume 15: 7131. CrossRef
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Thyroid Big Data Articles (National Health Insurance Service Database)
Graves’ Disease and the Risk of End-Stage Renal Disease: A Korean Population-Based Study: Yoon Young Cho, Bongseong Kim, Dong Wook Shin, Hye Ryoun Jang, Bo-Yeon Kim, Chan-Hee Jung, Jae Hyeon Kim, Sun Wook Kim, Jae Hoon Chung, Kyungdo Han, Tae Hyuk Kim; Endocrinol Metab. 2022;37(2):281-289. Published online April 6, 2022; DOI: https://doi.org/10.3803/EnM.2021.1333

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Background
Hyperthyroidism is associated with an increased glomerular filtration rate (GFR) in the hyperdynamic state, which is reversible after restoring euthyroidism. However, long-term follow-up of renal dysfunction in patients with hyperthyroidism has not been performed.
Methods
This was a retrospective cohort study using the Korean National Health Insurance database and biannual health checkup data. We included 41,778 Graves’ disease (GD) patients and 41,778 healthy controls, matched by age and sex. The incidences of end-stage renal disease (ESRD) were calculated in GD patients and controls. The cumulative dose and duration of antithyroid drugs (ATDs) were calculated for each patient and categorized into the highest, middle, and lowest tertiles.
Results
Among 41,778 GD patients, 55 ESRD cases occurred during 268,552 person-years of follow-up. Relative to the controls, regardless of smoking, drinking, or comorbidities, including chronic kidney disease, GD patients had a 47% lower risk of developing ESRD (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.37 to 0.76). In particular, GD patients with a higher baseline GFR (≥90 mL/min/1.73 m2; HR, 0.33; 95% CI, 0.11 to 0.99), longer treatment duration (>33 months; HR, 0.31; 95% CI, 0.17 to 0.58) or higher cumulative dose (>16,463 mg; HR, 0.29; 95% CI, 0.15 to 0.57) of ATDs had a significantly reduced risk of ESRD.
Conclusion
This was the first epidemiological study on the effect of GD on ESRD, and we demonstrated that GD population had a reduced risk for developing ESRD.

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Chronic Kidney Disease and Thyroid Hormones
Yuan Cheng, Haofei Hu, Wangyang Li, Sheng Nie, Shiyu Zhou, Yuna Chen, Tao Cao, Hong Xu, Bicheng Liu, Chunbo Chen, Huafeng Liu, Qiongqiong Yang, Hua Li, Yaozhong Kong, Guisen Li, Yan Zha, Ying Hu, Gang Xu, Yongjun Shi, Yilun Zhou, Guobin Su, Ying Tang, Men
The Journal of Clinical Endocrinology & Metabolism.2025; 110(8): e2446. CrossRef
Significance of pathological changes and chemokine expression in various organs in a Graves’ disease animal model
Yang Yang, Chen Hui
Journal of Molecular Histology.2025;[Epub] CrossRef
Kidney diseases and the thyroid: interactions and consequences
Gabriela Brenta
Nature Reviews Endocrinology.2025;[Epub] CrossRef
Renal function changes in patients with subclinical hyperthyroidism: a novel postulated mechanism
Magdy Mohamed Allam, Hanaa Tarek El-Zawawy, Tarek Hussein El-Zawawy
Endocrine.2023; 82(1): 78. CrossRef
Effect of Hyperthyroidism on Preventing Renal Insufficiency
Tae Yong Kim
Endocrinology and Metabolism.2022; 37(2): 220. CrossRef
Effects and Clinical Value of Peritoneal Dialysis on Water and Water Balance, Adverse Reactions, Quality of Life, and Clinical Prognosis in Patients with Decompensated Chronic Nephropathy: A Systematic Review and Meta-Analysis
Xichao Wang, Miaomiao Zhang, Na Sun, Wenxiu Chang, Gang Chen
Computational and Mathematical Methods in Medicine.2022; 2022: 1. CrossRef

Thyroid Big Data Articles (National Health Insurance Service Database)
Risk of Diabetes in Patients with Long-Standing Graves’ Disease: A Longitudinal Study: Eyun Song, Min Ji Koo, Eunjin Noh, Soon Young Hwang, Min Jeong Park, Jung A Kim, Eun Roh, Kyung Mook Choi, Sei Hyun Baik, Geum Joon Cho, Hye Jin Yoo; Endocrinol Metab. 2021;36(6):1277-1286. Published online December 16, 2021; DOI: https://doi.org/10.3803/EnM.2021.1251

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Background
The detrimental effects of excessive thyroid hormone on glucose metabolism have been widely investigated. However, the risk of diabetes in patients with long-standing hyperthyroidism, especially according to treatment modality, remains uncertain, with few longitudinal studies.
Methods
The risk of diabetes in patients with Graves’ disease treated with antithyroid drugs (ATDs) for longer than the conventional duration (≥2 years) was compared with that in age-and sex-matched controls. The risk was further compared according to subsequent treatment modalities after a 24-month course of ATD: continuation of ATD (ATD group) vs. radioactive iodine ablation (RIA) group.
Results
A total of 4,593 patients were included. Diabetes was diagnosed in 751 (16.3%) patients over a follow-up of 7.3 years. The hazard ratio (HR) for diabetes, after adjusting for various known risk factors, was 1.18 (95% confidence interval [CI], 1.10 to 1.28) in patients with hyperthyroidism. Among the treatment modality groups, the RIA group (n=102) had a higher risk of diabetes than the ATD group (n=4,491) with HR of 1.56 (95% CI, 1.01 to 2.42). Further, the risk of diabetes increased with an increase in the ATD treatment duration (P for trend=0.019).
Conclusion
The risk of diabetes was significantly higher in patients with long-standing Graves’ disease than in the general population, especially in patients who underwent RIA and prolonged ATD treatment. Special attention to hyperglycemia during follow-up along with effective control of hyperthyroidism may be necessary to reduce the risk of diabetes in these patients.

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Yoon Young Cho, Bongseong Kim, Sang-Man Jin, Chan-Hee Jung, Ji Oh Mok, Sun Wook Kim, Jae Hoon Chung, Kyung-Do Han, Tae Hyuk Kim
Thyroid®.2025; 35(1): 60. CrossRef
Diabetes mellitus secondary to endocrine diseases: a position statement of the working group of the club of the Italian society of endocrinology (SIE)-Nutrition hormones and metabolism
Luigi Barrea, Massimiliano Caprio, Sebastio Perrini, Elisabetta Camajani, Andrea Crafa, Elena Gangitano, Stefania Gorini, Laura Sciacca, Ludovica Verde, Manuela Albertelli, Diego Ferone, Francesco Giorgino, Annamaria Colao, Gianluca Aimaretti, Giovanna Mu
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Robert Krysiak, Karolina Kowalcze, Bogusław Okopień
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Safety of non-standard regimen of systemic steroid therapy in patients with Graves’ orbitopathy: a single-centre experience
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Increased risk of diabetes mellitus and hyperlipidemia in patients with differentiated thyroid cancer
Hwa Young Ahn, Jooyoung Lee, Jinmo Kang, Eun Kyung Lee
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Evaluation of the Dysregulation of Cholesterol and Glucose Levels in Graves' Disease Using Clinical Data Analysis
Zainab Razaq Kareem, Fatin Fadhel Al-Kazazz, Ahmed Mahdi Rheima, Ameer Radhi Sultan
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Juan J. Díez, Pedro Iglesias
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Juan J. Díez, Pedro Iglesias
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Mihaela Simona Popoviciu, Lorena Paduraru, Raluca Marinela Nutas, Alexandra Maria Ujoc, Galal Yahya, Kamel Metwally, Simona Cavalu
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Roshmi Gupta, Pramila Kalra, Lakshmi B. Ramamurthy, Suryasnata Rath
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Diabetes and Hyperthyroidism: Is There a Causal Link?
Sang Yong Kim
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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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Young Ju Choi, Kyungdo Han, Won Kyoung Cho, Min Ho Jung, Byung-Kyu Suh
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Table of Contents

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Yanrui Huang, Haixia Guan
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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
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Review Article

Thyroid
Antithyroid Drug Treatment in Graves’ Disease: Jae Hoon Chung; Endocrinol Metab. 2021;36(3):491-499. Published online June 16, 2021; DOI: https://doi.org/10.3803/EnM.2021.1070

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Graves’ disease is associated with thyrotropin (TSH) receptor stimulating antibody, for which there is no therapeutic agent. This disease is currently treated through inhibition of thyroid hormone synthesis or destruction of the thyroid gland. Recurrence after antithyroid drug (ATD) treatment is common. Recent studies have shown that the longer is the duration of use of ATD, the higher is the remission rate. Considering the relationship between clinical outcomes and iodine intake, recurrence of Graves’ disease is more common in iodine-deficient areas than in iodine-sufficient areas. Iodine restriction in an iodine-excessive area does not improve the effectiveness of ATD or increase remission rates. Recently, Danish and Korean nationwide studies noted significantly higher prevalence of birth defects in newborns exposed to ATD during the first trimester compared to that of those who did not have such exposure. The prevalence of birth defects was lowest when propylthiouracil (PTU) was used and decreased by only 0.15% when methimazole was changed to PTU in the first trimester. Therefore, it is best not to use ATD in the first trimester or to change to PTU before pregnancy.

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Original Articles

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.

Citations

Citations to this article as recorded by

Association of PD-1 (rs36084323) gene polymorphism with autoimmune thyroid diseases
Nora M. Elkady, Ahmed A. Elzeiny, Mona A. Abd El-Raouf, Dina Elzeiny, Basma.Z. El-Morsy, Sherin Z. Mohamed, Dalia Kamal Nassar
Human Immunology.2026; 87(1): 111618. CrossRef
Synergistic effects of BTN3A1, SHP2, CD274, and STAT3 gene polymorphisms on the risk of systemic lupus erythematosus: a multifactorial dimensional reduction analysis
Yang-Yang Tang, Wang-Dong Xu, Lu Fu, Xiao-Yan Liu, An-Fang Huang
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Clinical Characteristics of Graves' Disease Patients with Undetectable Thyrotropin Binding Inhibitor Immunoglubulin (TB2).: Bo Youn Cho, Won Bae Kim, Hong Gyu Lee, Chang Soon Koh, Seong Yeon Kim, Seok In Lee, Jae Seok Chun, Kyung Soo Park; J Korean Endocr Soc. 1996;11(1):68-74. Published online November 7, 2019

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Abstract PDF: Background
Graves disease is an autoimmune disease caused by TSH receptor antibodies. Thyrotropin binding inhibitor immunoglobulins(TBII) are detected in most Graves patients, but some patients have no TBII activities in their sera. It is unknown whether the clinical features of TBII-positive patients are different from those of TBII-negative patients. Methods: To evaluate the prevalence of TBII-negative Graves' patients and its clinical differences from TBII-positive patients, we examined TBII by radioreceptor assay in 686 consecutive untreated Graves patients. We found 84 TBII-negative patients(15 men and 69 women, mean age ±EM: 40.9±.4 years) and compared their clinical characteristics with 87 TBII-positive patients (22 men and 65 women, mean age±EM: 39.9±.5 years) who were selected randomly from the same patients group. Results: In this study, TBII was undetectable in 12.2% of patients with Graves' disease(84 of 686). TBII-negative group had a less weight loss than TBII-positive group. However, there was no significant differences in age, sex ratio, prevalence of ophthalmopathy, duration of illness and positive rate of family history for thyroid diseases between TBII-negative and -positive groups. Serum total T or T levels were not different from each other, but T3-uptake was significantly higher in TBII-positive group than that in TBII-negative group, suggesting that the free hormone levels in TBII-negative group might be lower. The thyroid uptake of 99mTcO4 was significantly higher in TBII positive group than that in TBII-negative group. Thyroid autoantibodies, including antimicrosomal and antithyroglobulin antibodies were detected in almost all patients but there were no differences in titers and positive rate between TBII-negative and -positive groups. Conclusion: Although TBII-negative Graves patients showed less weight loss and low 99mTc04 thyroidal uptake compare to TBII-positive patients, the clinical and immunological characteristics of TBII-negative patients are not different from TBII-positive one.

Difference of Thyroid Stimulating Antidody Activities Measured in Chinese Hamster Ovary Cells Stably Transfected with Human TSH Receptor and in FRTL-5 Cells in Graves Disease and Its Clinical Correlations.: Young Kee Shong Young Kee Shong, Hye Young Park, Bo Youn Cho, Won Bae Kim, Hong Gyu Lee, Chang Soon Koh, Yeon Sang Oh; J Korean Endocr Soc. 1996;11(1):18-29. Published online November 7, 2019

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Abstract PDF: Background
: Thyroid stimulating antibodies result in the development of hyperthyroidism and goiter in Graves disease. However, thyroid stimulating antibody activities do not correlate with the clinical features in many patients with Graves disease. The purpose of this study is to address this discrepancy between thyroid stimulating antibody activities and clinical features of Graves patients. Methods: We measured thyroid stimulating antibody activities simultaneously using human TSH receptor transfected Chinese hamster(hTSHR-CHO) cells and rat thyroid(FRTL-5) cells in 57 untreated patients with Graves disease, and compared their activities with clinical features including thyroid hormone levels. Results : The detection rate of thyroid stimulating antibody measured by hTSHR-CHO cells was 90% in 57 untreated Graves patients and it was higher than that measured by FRTL-5 cells. Thyroid stimulating antibody activity by hTSHR-CHO cells was significantly correlated with that by FRTL-5 cells(r=0.5, p<0.001), however, 18 of 57(32%) patients showed marked discrepancy of thyroid stimulating antibody activity between in hTSHR-CHO and FRTL-5 systems. Thyroid stimulating antibody activity measured by hTSHR-CHO cells was significantly correlated with serum total T3, free T4 levels, and goiter size but not 99mTc-thyroid uptake. On the other hand, thyroid stimulating antibody activity measured by FRTL-5 cells was significantly correlated with goiter size and 99mTc-thyroid uptake but not thyroid hormone levels. The difference between function and goiter size with respect to thyroid stimulating antibody measurement in two cells system is, nevertheless, particularly evident in the free T4/goiter ratio in patients with high hTSHR-CHO and low FRTL-5 cell assay values. Conclusion: These findings suggest that thyroid stimulating antibodies in Graves disease are heterogeneous population in terms of responses to different origin of cells. Further, thyroid stimulating antibody activities measured by FRTL-5 cells tend to correlate better with goiter size and Tc-thyroid uptake, whereas thyroid stimulating antibody activities measured by hTSH-CHO cells correlate better with thyroid hormone levels.

Clinical Study
Changes in Thyroid Peroxidase and Thyroglobulin Antibodies Might Be Associated with Graves' Disease Relapse after Antithyroid Drug Therapy: Yun Mi Choi, Mi Kyung Kwak, Sang Mo Hong, Eun-Gyoung Hong; Endocrinol Metab. 2019;34(3):268-274. Published online September 26, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.3.268

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Background

Graves' disease (GD) is an autoimmune thyroid disorder caused by antibodies stimulating the thyrotropin (TSH) receptor. TSH receptor antibody (TRAb) measurement is useful for predicting GD relapse after antithyroid drug (ATD) treatment. However, the association of other thyroid autoantibodies with GD relapse remains obscure.

Methods

This retrospective study enrolled patients with GD who were initially treated with ATD. TRAb, thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) were measured at the initial diagnosis and at the time of ATD discontinuation.

Results

A total of 55 patients were enrolled. The mean age was 49.7 years, and 39 patients (70.9%) were female. Antibody positivity at diagnosis was 90.9%, 69.1%, and 61.9% for TRAb, TPOAb, TgAb, respectively. Median ATD treatment period was 15.1 months. At the time of ATD withdrawal, TRAb titers decreased uniformly overall. Conversely, TPOAb and TgAb showed various changes. After withdrawal of ATD, 19 patients (34.5%) experienced relapse. No clinical features or laboratory results were significantly related to relapse in the overall patient group. However, in the TPOAb positive group at diagnosis, increasing titer of TPOAb or TgAb after ATD treatment was significantly and independently related to relapse free survival (TPOAb: hazard ratio [HR], 17.99; 95% confidence interval [CI], 1.66 to 195.43; P=0.02) (TgAb: HR, 5.73; 95% CI, 1.21 to 27.26; P=0.03).

Conclusion

Changes in TPOAb or TgAb titers during treatment might be useful for predicting relapse after ATD treatment in patients with positive TPOAb at diagnosis.

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Programmed Cell Death-Ligand 1 (PD-L1) gene Single Nucleotide Polymorphism in Graves’ Disease and Hashimoto’s Thyroiditis in Korean Patients
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Low frequency of IL-10-producing B cells and high density of ILC2s contribute to the pathological process in Graves’ disease, which may be related to elevated-TRAb levels
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Review Article

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

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

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Original Article

Free Thyroxine, Anti-Thyroid Stimulating Hormone Receptor Antibody Titers, and Absence of Goiter Were Associated with Responsiveness to Methimazole in Patients with New Onset Graves' Disease: Hoon Sung Choi, Won Sang Yoo; Endocrinol Metab. 2017;32(2):281-287. Published online June 23, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.2.281

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Background

Anti-thyroid drug therapy is considered a treatment of choice for Graves' disease; however, treatment response varies among individuals. Although several studies have reported risk factors for relapse after initial treatment, few have assessed responsiveness during the early treatment period. Our study aimed to identify the clinical characteristics for responsiveness to methimazole.

Methods

We included 99 patients diagnosed with Graves' disease for the first time. Drug responsiveness was defined as the correlation coefficients between decreasing rates of free thyroxine level per month and methimazole exposure dose. According to their responsiveness to treatment, the patients were classified into rapid or slow responder groups, and age, sex, free thyroxine level, and thyrotropin binding inhibiting immunoglobulin (TBII) titers were compared between groups.

Results

The mean patient age was 44.0±13.5 years and 40 patients were male (40%). The mean TBII titer was 36.6±74.4 IU/L, and the mean free thyroxine concentration was 48.9±21.9 pmol/L. The rapid responder group showed higher TBII titer and free thyroxine level at diagnosis, while age, sex, smoking, and presence of goiter did not differ between the two groups. Logistic regression analyses revealed that high level of serum thyroxine, high titer of TBII, and absence of goiter were significantly associated with a rapid response, while age, sex, and smoking were not significant factors for the prediction of responsiveness.

Conclusion

In patients with new onset Graves' disease, high level of free thyroxine, high titer of TBII, and absence of goiter were associated with rapid responsiveness to methimazole treatment.

Citations

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When should antithyroid drug therapy to reduce the relapse rate of hyperthyroidism in Graves’ disease be discontinued?
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Review Article

Thyroid
Recent Advances in Autoimmune Thyroid Diseases: Won Sang Yoo, Hyun Kyung Chung; Endocrinol Metab. 2016;31(3):379-385. Published online August 26, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.3.379

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Autoimmune thyroid disease (AITD) includes hyperthyroid Graves disease, hypothyroid autoimmune thyroiditis, and subtle subclinical thyroid dysfunctions. AITD is caused by interactions between genetic and environmental predisposing factors and results in autoimmune deterioration. Data on polymorphisms in the AITD susceptibility genes, related environmental factors, and dysregulation of autoimmune processes have accumulated over time. Over the last decade, there has been progress in the clinical field of AITD with respect to the available diagnostic and therapeutic methods as well as clinical consensus. The updated clinical guidelines allow practitioners to identify the most reasonable and current approaches for proper management. In this review, we focus on recent advances in understanding the genetic and environmental pathogenic mechanisms underlying AITD and introduce the updated set of clinical guidelines for AITD management. We also discuss other aspects of the disease such as management of subclinical thyroid dysfunction, use of levothyroxine plus levotriiodothyronine in the treatment of autoimmune hypothyroidism, risk assessment of long-standing antithyroid drug therapy in recurrent Graves' hyperthyroidism, and future research needs.

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Brief Report

Thyroid
Cholestyramine Use for Rapid Reversion to Euthyroid States in Patients with Thyrotoxicosis: Jeonghoon Ha, Kwanhoon Jo, Borami Kang, Min-Hee Kim, Dong-Jun Lim; Endocrinol Metab. 2016;31(3):476-479. Published online July 26, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.3.476

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Cholestyramine (CS) is an ion exchange resin, which binds to iodothyronines and would lower serum thyroid hormone level. The use of CS added to conventional antithyroid drugs to control thyrotoxicosis has been applied since 1980's, and several studies indicate that using CS in combination with methimazole (MZ) produces a more rapid decline in serum thyroid hormones than with only MZ treatment. Our recent retrospective review of five patients taking high dose MZ and CS, compared to age-, gender-, initial free thyroxine (T4) level-, and MZ dose-matched 12 patients with MZ use only, showed more rapid decline of both free T4 and triiodothyronine levels without more adverse events. CS could be safely applicable short-term adjunctive therapy when first-line antithyroid medications are not enough to adequately control severe thyrotoxicosis or side effects of antithyroid drug would be of great concern.

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Original Articles

Clinical Study
Usefulness of Measuring Thyroid Stimulating Antibody at the Time of Antithyroid Drug Withdrawal for Predicting Relapse of Graves Disease: Hyemi Kwon, Won Gu Kim, Eun Kyung Jang, Mijin Kim, Suyeon Park, Min Ji Jeon, Tae Yong Kim, Jin-Sook Ryu, Young Kee Shong, Won Bae Kim; Endocrinol Metab. 2016;31(2):300-310. Published online April 25, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.2.300

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Background

Hyperthyroidism relapse in Graves disease after antithyroid drug (ATD) withdrawal is common; however, measuring the thyrotropin receptor antibody (TRAb) at ATD withdrawal in order to predict outcomes is controversial. This study compared measurement of thyroid stimulatory antibody (TSAb) and thyrotropin-binding inhibitory immunoglobulin (TBII) at ATD withdrawal to predict relapse.

Methods

This retrospective study enrolled patients with Graves disease who were treated with ATDs and whose serum thyroid-stimulating hormone levels were normal after receiving low-dose ATDs. ATD therapy was stopped irrespective of TRAb positivity after an additional 6 months of receiving the minimum dose of ATD therapy. Patients were followed using thyroid function tests and TSAb (TSAb group; n=35) or TBII (TBII group; n=39) every 3 to 6 months for 2 years after ATD withdrawal.

Results

Twenty-eight patients (38%) relapsed for a median follow-up of 21 months, and there were no differences in baseline clinical characteristics between groups. In the TSAb group, relapse was more common in patients with positive TSAb at ATD withdrawal (67%) than patients with negative TSAb (17%; P=0.007). Relapse-free survival was shorter in TSAb-positive patients. In the TBII group, there were no differences in the relapse rate and relapse-free survivals according to TBII positivity. For predicting Graves disease relapse, the sensitivity and specificity of TSAb were 63% and 83%, respectively, whereas those of TBII were 28% and 65%.

Conclusion

TSAb at ATD withdrawal can predict the relapse of Graves hyperthyroidism, but TBII cannot. Measuring TSAb at ATD withdrawal can assist with clinical decisions making for patients with Graves disease.

Citations

Citations to this article as recorded by

US-based, Prospective, Blinded Study of Thyrotropin Receptor Antibody in Autoimmune Thyroid Disease
Mark A Lupo, Paul D Olivo, Maximilian Luffy, Jan Wolf, George J Kahaly
The Journal of Clinical Endocrinology & Metabolism.2025; 110(5): e1619. CrossRef
Significance of Thyroid-Stimulating Immunoglobulin and Thyrotropin Receptor Antibody in Graves Disease
Rongguang Peng, Pu Xie, Zhou Jin, Wenzhong Zhou, Yanqiu Wang, Xinxin Chen, Qinglei Yin, Liyun Shen, Lingyang Meng, Lei Ye, Yulin Zhou, Shu Wang
The Journal of Clinical Endocrinology & Metabolism.2025; 110(9): e3002. CrossRef
Comparative efficacy and safety of rituximab, tocilizumab, and teprotumumab in Graves’ orbitopathy: a systematic review and meta-analysis
Abdulelah G. Abumohssin, Rayan A. Alshareef, Saja Aljohani, Abdulrahman Alqutub, Abdulsalam Alqutub
Eye.2025; 39(10): 1901. CrossRef
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Thyroid-stimulating immunoglobulin levels during low-dose antithyroid therapy predict Graves’ disease relapse
Phong Vu Nhat Nguyen, Khue Thy Nguyen
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Thyroid stimulating receptor autoantibodies
Yumeng Gao, Ling Qiu, Songlin Yu, Xinqi Cheng
Clinica Chimica Acta.2024; 559: 119700. CrossRef
Dynamic Risk Model for the Medical Treatment of Graves’ Hyperthyroidism according to Treatment Duration
Meihua Jin, Chae A Kim, Min Ji Jeon, Won Bae Kim, Tae Yong Kim, Won Gu Kim
Endocrinology and Metabolism.2024; 39(4): 579. CrossRef
Comparison between thyroid stimulating immunoglobulin and TSH-receptor antibodies in the diagnosis and management of Graves’ disease
Peiwei Yao, Yunliang Xie, Yunlin Wang, Chunyan Liang, Bingwen Huang
Frontiers in Endocrinology.2024;[Epub] CrossRef
Analysis of Related Factors in Refractory Graves’ Disease
鑫王
Advances in Clinical Medicine.2023; 13(08): 13439. CrossRef
Interpretation of Thyroid Autoantibodies in Hyperthyroidism
Han-Sang Baek, Dong-Jun Lim
The Korean Journal of Medicine.2023; 98(3): 132. CrossRef
The Early Changes in Thyroid-Stimulating Immunoglobulin Bioassay over Anti-Thyroid Drug Treatment Could Predict Prognosis of Graves’ Disease
Jin Yu, Han-Sang Baek, Chaiho Jeong, Kwanhoon Jo, Jeongmin Lee, Jeonghoon Ha, Min Hee Kim, Jungmin Lee, Dong-Jun Lim
Endocrinology and Metabolism.2023; 38(3): 338. CrossRef
Prediction of the recurrence risk of Graves' disease after antithyroid drug therapy
Qiang Zhang, Ying Fu
Environmental Disease.2023; 8(1): 7. CrossRef
Thyroid-Stimulatory Antibody as a Predictive Factor for Graves’ Disease Relapse
Tiago Da Silva Santos, José Carlos Oliveira, Cláudia Freitas, André Couto de Carvalho
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The Prediction Model Using Thyroid-stimulating Immunoglobulin Bioassay For Relapse of Graves’ Disease
Han-Sang Baek, Jaejun Lee, Chai-Ho Jeong, Jeongmin Lee, Jeonghoon Ha, Kwanhoon Jo, Min-Hee Kim, Jae Hyoung Cho, Moo Il Kang, Dong-Jun Lim
Journal of the Endocrine Society.2022;[Epub] CrossRef
Identification of patients with Graves’ disease who benefit from high-dose radioactive iodine therapy
Shiro Watanabe, Shozo Okamoto, Kazumasa Akikawa, Noriyuki Miyamoto, Miyuki Okamura-Kawasaki, Yuko Uchiyama, Junki Takenaka, Takuya Toyonaga, Kenji Hirata, Kohsuke Kudo
Annals of Nuclear Medicine.2022; 36(11): 923. CrossRef
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Xinxin Zhu, Yaguang Zhang, Xiaoyu Zhao, Xiaona Zhang, Zixuan Ru, Yanmeizhi Wu, Xu Yang, Boyu Hou, Hong Qiao
Frontiers in Cardiovascular Medicine.2022;[Epub] CrossRef
Antithyroid Drug Treatment in Graves’ Disease
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Endocrinology and Metabolism.2021; 36(3): 491. CrossRef
The prognostic value of thyroid-stimulating immunoglobulin in the management of Graves’ disease
Yulin Zhou, Mengxi Zhou, Yicheng Qi, Weiqing Wang, Xinxin Chen, Shu Wang
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Changes in Thyroid Peroxidase and Thyroglobulin Antibodies Might Be Associated with Graves' Disease Relapse after Antithyroid Drug Therapy
Yun Mi Choi, Mi Kyung Kwak, Sang Mo Hong, Eun-Gyoung Hong
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International Journal of Thyroidology.2019; 12(2): 79. CrossRef
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Endocrine.2019; 65(2): 348. CrossRef
Elevated Serum IL-17 Expression at Cessation Associated with Graves’ Disease Relapse
Jianhui Li, Xiaohua Sun, Danzhen Yao, Jinying Xia
International Journal of Endocrinology.2018; 2018: 1. CrossRef
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Hyemi Kwon, Hye-Seon Oh, Mijin Kim, Suyeon Park, Min Ji Jeon, Won Gu Kim, Won Bae Kim, Young Kee Shong, Dong Eun Song, Jung Hwan Baek, Ki-Wook Chung, Tae Yong Kim
The Journal of Clinical Endocrinology & Metabolism.2017; 102(6): 1917. CrossRef
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Hoon Sung Choi, Won Sang Yoo
Endocrinology and Metabolism.2017; 32(2): 281. CrossRef
The Second Antithyroid Drug Treatment Is Effective in Relapsed Graves' Disease Patients: A Median 11-Year Follow-Up Study
Ye An Kim, Sun Wook Cho, Hoon Sung Choi, Shinje Moon, Jae Hoon Moon, Kyung Won Kim, Do Joon Park, Ka Hee Yi, Young Joo Park, Bo Youn Cho
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International Journal of Thyroidology.2017; 10(2): 77. CrossRef
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Clinical Study
Comparison of Fixed versus Calculated Activity of Radioiodine for the Treatment of Graves Disease in Adults: Abigail U. Canto, Paulette N. Dominguez, Cecilia A. Jimeno, Jerry M. Obaldo, Ruben V. Ogbac; Endocrinol Metab. 2016;31(1):168-173. Published online March 16, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.1.168

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Background

Radioactive iodine as a treatment modality has been shown in several studies to be a safe and effective therapy for Graves disease. However, there is still no uniformity regarding optimal dosing method. The aim of this study is to compare the efficacy of calculated and fixed dosing of radioiodine for the treatment of Graves disease.

Methods

A hundred twenty-two patients diagnosed with Graves disease were randomized to receive either fixed or calculated dose of radioiodine. Those randomized to fixed activity received either low fixed activity at 9.9 mCi for thyroid gland size <40 g or high fixed activity at 14.9 mCi for thyroid gland size 40 to 80 g, and those grouped to calculated activity received 160 µCi/g of thyroid tissue adjusted for 24 hours radioiodine uptake. Thyroid function tests (free thyroxine [T4] and thyroid stimulating hormone [TSH]) were monitored at 10, 16, and 24 weeks after radioactive iodine therapy. The primary outcome, treatment failure was defined as persistently elevated free T4 and low TSH.

Results

Of the 122 patients randomized, 56 in the fixed dose group and 56 in the calculated dose group completed the follow-up. At the end of 6 months, the percentage of treatment failure was 37.50% in the calculated dose group versus 19.64% in the fixed dose group with a relative risk of 0.53 (95% confidence interval, 0.28 to 0.98) favoring the fixed dose group.

Conclusion

Fixed dose radioiodine has a significantly lower incidence of persistent hyperthyroidism at 6 months post-radioactive therapy.

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Busra Kuyumcu Demir, Ersen Karakilic, Emre Sedar Saygili, Nilgun Araci, Semra Ozdemir
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Valentina Dini, Massimo Salvatori, Mauro Belli, Maria Elena Lago, Alessandra Nosdeo, Donatella Pia Dambra, Luisa Lo Conte, Ilaria Pecchia, Alessandro Giordano
International Journal of Molecular Sciences.2022; 23(17): 10156. CrossRef
Current controversies in the management of Graves’ hyperthyroidism
Niroshan Francis, Thanuya Francis, John H Lazarus, Onyebuchi E Okosieme
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Effect of Different 131I Dose Strategies for Treatment of Hyperthyroidism on Graves’ Ophthalmopathy
Shahrara Ariamanesh, Narjess Ayati, Zahra Mazloum Khorasani, Zohreh Mousavi, Victoria Kiavash, Zahra Kiamanesh, Seyed Rasoul Zakavi
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Zhao Lina, Zhang Wenqi, Xin Yubo, Wen Qiang, Bail Lin, Guan Feng, Ji Bin
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Case Report

Thyroid
Refractory Graves' Disease Successfully Cured by Adjunctive Cholestyramine and Subsequent Total Thyroidectomy: Yeoree Yang, Seawon Hwang, Minji Kim, Yejee Lim, Min-Hee Kim, Sohee Lee, Dong-Jun Lim, Moo-Il Kang, Bong-Yun Cha; Endocrinol Metab. 2015;30(4):620-625. Published online December 31, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.4.620

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The three major forms of treatment for Graves thyrotoxicosis are antithyroid drugs, radioactive iodine therapy and thyroidectomy. Surgery is the definitive treatment for Graves thyrotoxicosis that is generally recommended when other treatments have failed or are contraindicated. Generally, thyrotoxic patients should be euthyroid before surgery to minimize potential complications which usually requires preoperative management with thionamides or inorganic iodine. But several cases of refractory Graves' disease have shown resistance to conventional treatment. Here we report a 40-year-old female patient with Graves' disease who complained of thyrotoxic symptoms for 7 months. Her thyroid function test and thyroid autoantibody profiles were consistent with Graves' disease. One kind of thionamides and β-blocker were started to control her disease. However, she was resistant to nearly all conventional medical therapies, including β-blockers, inorganic iodine, and two thionamides. She experienced hepatotoxicity from the thionamides. What was worse is her past history of serious allergic reaction to corticosteroids, which are often used to help control symptoms. A 2-week regimen of high-dose cholestyramine improved her uncontrolled thyrotoxicosis and subsequent thyroidectomy was successfully performed. In conclusion, cholestyramine could be administered as an effective and safe adjunctive agent for preoperative preparation in patients with severe hyperthyroid Graves's disease that is resistant to conventional therapies.

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Xinpan Wang, Tiantian Li, Yue Li, Qiuyi Wang, Yun Cai, Zhixiao Wang, Yun Shi, Tao Yang, Xuqin Zheng
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Refractory Graves’ Disease in an Adolescent Successfully Treated With Cholestyramine and Subsequent Thyroidectomy
Raghad Alsaidalani, Hesham Eltomy, Alaa B Aljuhani, Moutaz Osman
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Non-thionamide antithyroid drug options in Graves’ hyperthyroidism
Aliya Ruslan, Onyebuchi E Okosieme
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Daniela Gallo, Federica Martina Bianchi, Francesca Manzella La Barbera, Ilaria Clementi, Adriana Lai, Eliana Piantanida, Maria Laura Tanda
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Fateen Ata, Adeel Ahmad Khan, Shuja Tahir, Zaina Al Amer
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Lorenzo SCAPPATICCIO, Giuseppe BELLASTELLA, Maria I. MAIORINO, Luca GIOVANELLA, Katherine ESPOSITO
The Quarterly Journal of Nuclear Medicine and Molecular Imaging.2021;[Epub] CrossRef
THERAPEUTIC EFFECTS OF COMBINATION REGIMENS INCLUDING METHIMAZOLE ON GRAVES HYPERTHYROIDISM: A NETWORK META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Maorong Wang, Yerong Yu
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Cholestyramine alters bile acid amounts and the expression of cholesterol‐related genes in rabbit intestinal and hepatic tissues
Dong Ni Qiu, Quan Shang, Da Yu Sun, Wei Qun Ding, Zhong Guang Luo, Jian Chen, Wei Ru Jiang, Jian Ping Huang, Xiao Yun Jiang
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ENDOCRINOLOGY IN PREGNANCY: Pregnancy and the incidence, diagnosing and therapy of Graves’ disease
Peter Laurberg, Stine Linding Andersen
European Journal of Endocrinology.2016; 175(5): R219. CrossRef
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
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Jeonghoon Ha, Kwanhoon Jo, Borami Kang, Min-Hee Kim, Dong-Jun Lim
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Libor Vítek, Martin Haluzík
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Original Article

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.

Citations

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MICA polymorphisms associated with antithyroid drug‐induced agranulocytosis in the Chinese Han population
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Increased Risk of Antithyroid Drug Agranulocytosis Associated with Amiodarone-Induced Thyrotoxicosis: A Population-Based Cohort Study
Michal Gershinsky, Walid Saliba, Idit Lavi, Chen Shapira, Naomi Gronich
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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
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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
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Review Article

Thyroid
The Diagnosis and Management of Hyperthyroidism in Korea: Consensus Report of the Korean Thyroid Association: Jae Hoon Moon, Ka Hee Yi; Endocrinol Metab. 2013;28(4):275-279. Published online December 12, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.4.275

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Hyperthyroidism is one of the causes of thyrotoxicosis and the most common cause of hyperthyroidism in Korea is Graves disease. The diagnosis and treatment of Graves disease are different according to geographical area. Recently, the American Thyroid Association and the American Association of Clinical Endocrinologists suggested new management guidelines for hyperthyroidism. However, these guidelines are different from clinical practice in Korea and are difficult to apply. Therefore, the Korean Thyroid Association (KTA) conducted a survey of KTA members regarding the diagnosis and treatment of hyperthyroidism, and reported the consensus on the management of hyperthyroidism. In this review, we summarized the KTA report on the contemporary practice patterns in the diagnosis and management of hyperthyroidism, and compared this report with guidelines from other countries.

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Case Reports

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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Abstract PDF PubReader

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.

Citations

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Management of Riedel Thyroiditis With Completion Thyroidectomy to Relieve Persistent Compressive Symptoms
Alice S Win, Katarina A Topchyan, Philip W Smith, David C Shonka, Richard J Santen, William B Horton
JCEM Case Reports.2025;[Epub] CrossRef
IgG4-Mediated Sclerosing Riedel Thyroiditis: A Multidisciplinary Case Study and Literature Review
Dumitru Ioachim, Mihai Alin Publik, Dana Terzea, Carmen Adina Cristea, Adina Mariana Ghemigian, Anda Dumitrascu, Eugenia Petrova, Alexandra Voinea, Romeo Smarandache, Mihail Ceausu
International Journal of Molecular Sciences.2025; 26(16): 7786. CrossRef
IgG4-related sclerosing thyroiditis (Riedel-Struma): a review of clinicopathological features and management
Agata Czarnywojtek, Krzysztof Pietrończyk, Lester D. R. Thompson, Asterios Triantafyllou, Ewa Florek, Nadia Sawicka-Gutaj, Marek Ruchała, Maria Teresa Płazinska, Iain J. Nixon, Ashok R. Shaha, Mark Zafereo, Gregory William Randolph, Peter Angelos, Abir Al
Virchows Archiv.2023; 483(2): 133. CrossRef
Immunoglobulin G4-Related Thyroid Disease: A Single-Center Experience and Literature Review
Meihua Jin, Bictdeun Kim, Ahreum Jang, Min Ji Jeon, Young Jun Choi, Yu-Mi Lee, Dong Eun Song, Won Gu Kim
Endocrinology and Metabolism.2022; 37(2): 312. CrossRef
Riedel Thyroiditis
Aakansha Zala, Thomas Berhane, C Christofer Juhlin, Jan Calissendorff, Henrik Falhammar
The Journal of Clinical Endocrinology & Metabolism.2020; 105(9): e3469. CrossRef
Brief Review of Articles in 'Endocrinology and Metabolism' in 2013
Won-Young Lee
Endocrinology and Metabolism.2014; 29(3): 251. CrossRef

Thyroid
Anaplastic Thyroid Carcinoma Following Radioactive Iodine Therapy for Graves' Disease: Sun Hwa Kim, Hee Young Kim, Kwang Yoon Jung, Dong Seop Choi, Sin Gon Kim; Endocrinol Metab. 2013;28(1):61-64. Published online March 25, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.1.61

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Abstract PDF PubReader

Radioactive iodine (RAI) therapy has been used as a treatment option for Graves' disease, and it has been widely accepted to be safe. On the other hand, some evidence suggests that RAI therapy is possibly associated with a small increased risk of thyroid cancer. Herein, we report a rare case of anaplastic thyroid carcinoma (ATC) associated with Graves' disease, following RAI treatment. A 42-year-old woman had been diagnosed with Graves' disease and although she was treated with an antithyroid drug, she remained in a hyperthyroid state, which led to two RAI treatments. More than 10 years later, the patient revisited our clinic due to hoarseness, dysphagia, and dyspnea, which had lasted for 2 months. Neck computed tomography suggested thyroid carcinoma and a lymph node biopsy showed metastatic papillary carcinoma. The patient underwent total thyroidectomy and was finally diagnosed as having an ATC. It is not clear if the occurrence of ATC reported here was influenced by the RAI therapy or alternatively, it may only represent the delayed recognition of a rare change in the natural history of Graves' disease. Nevertheless, this report is worthwhile since it presents a very rare case of ATC that occurred eleven years after the RAI therapy for Graves' disease.

Citations

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Occurrence of Newly Diagnosed Thyroid Cancer Is Not Increased After Radioactive Iodine Therapy for Graves' Disease
Shigenori Hiruma, Natsuko Watanabe, Jaeduk Yoshimura Noh, Rei Hirose, Masakazu Koshibu, Masahiro Ichikawa, Akiko Sankoda, Hideyuki Imai, Yoshiyuki Saito, Nami Suzuki, Chie Masaki, Masako Matsumoto, Miho Fukushita, Ai Yoshihara, Kenichi Matsuzu, Hiroto Nar
The Journal of Clinical Endocrinology & Metabolism.2025; 110(12): 3441. CrossRef
V600E BRAF-mutated anaplastic thyroid carcinoma after radioactive iodine for Graves’ disease: a case report and a review of the literature
Marta Villanova, Luigi di Filippo, Filippo Maria Bolamperti, Carlo Rodella, Laura Castellino, Raffaele Giubbini
Clinical and Translational Imaging.2024; 12(5): 467. CrossRef
Evaluation of ultrasonographical and cytological features of thyroid nodules in patients treated with radioactive iodine for hyperthyroidism
Muhammet C. Bilginer, Didem Ozdemir, Fatma N. C. Seyrek, Nilufer Yildirim, Aylin K. Yazgan, Mehmet Kilic, Reyhan Ersoy, Bekir Cakir
Diagnostic Cytopathology.2020; 48(1): 3. CrossRef
Papillary thyroid carcinoma in cervical lymph nodes with vanished thyroid gland after ablation of Graves’ disease by radioactive iodine
O Hamdy, S Raafat, GA Saleh, K Atallah, Mahmoud M Saleh, AM Shebl, MA Hegazy
The Annals of The Royal College of Surgeons of England.2019; 101(5): e122. CrossRef
Brief Review of Articles in 'Endocrinology and Metabolism' in 2013
Won-Young Lee
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Thyroid
Two Cases of Methimazole-Induced Insulin Autoimmune Syndrome in Graves' Disease: Eun Roh, Ye An Kim, Eu Jeong Ku, Jae Hyun Bae, Hye Mi Kim, Young Min Cho, Young Joo Park, Kyong Soo Park, Seong Yeon Kim, Soo Heon Kwak; Endocrinol Metab. 2013;28(1):55-60. Published online March 25, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.1.55

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21 Crossref

Abstract PDF PubReader

We report here the cases of two females with Graves' disease who developed insulin autoimmune syndrome after treatment with methimazole. The patients exhibited a sudden altered mental state after treatment with methimazole for approximately 4 weeks. Patients had hypoglycemia with serum glucose below 70 mg/dL, and laboratory findings showed both high levels of serum insulin and high titers of insulin autoantibodies. The two women had never been exposed to insulin or oral antidiabetic agents, and there was no evidence of insulinoma in imaging studies. After glucose loading, serum glucose, and total insulin levels increased abnormally. One of the patient was found to have HLA-DRB1*0406, which is known to be strongly associated with methimazole-induced insulin autoimmune syndrome. After discontinuation of methimazole, hypoglycemic events disappeared within 1 month. Insulin autoantibody titer and insulin levels decreased within 5 months and there was no further development of hypoglycemic events. We present these cases with a review of the relevant literature.

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A Case of Painless Thyroiditis Followed by Graves' Disease.: Gyeong Jae Na, Ji Hyun Kim, Se Yoon Park, Ki Won Kim, Hee Ja Ko, Sung Wan Jeon, Yeo Joo Kim, Sang Jin Kim; Endocrinol Metab. 2012;27(2):147-150. Published online June 20, 2012; DOI: https://doi.org/10.3803/EnM.2012.27.2.147

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Abstract PDF

A 30-year-old man was admitted to our hospital because of fatigue, palpitation and severe weakness of both legs. The admission laboratory findings revealed thyrotoxicosis, and 131I thyroid scintigraphic imaging revealed a low radioactive iodine uptake. He was treated for painless thyroiditis for about 4 months. However, thyrotoxic state had continued and radioactive iodine uptake was markedly increased in the follow up scan. Painless thyroiditis often relapses, but rarely develops into Graves' disease. This is a rare case in which painless thyroiditis was followed by Graves' disease.

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A Case of Severe Recurrent Painless Thyroiditis Requiring Thyroidectomy
So Hyun Park, Il Seong Nam-Goong, Young Il Kim, Yun Sun Kim, Yung Min Kim, Eun Sook Kim
Journal of Korean Thyroid Association.2015; 8(1): 113. CrossRef

A Case of Acromegaly with Graves' Disease.: Jae Hoon Chung, Kwang Won Kim, Byoung Joon Kim, Sung Hoon Kim, Myung Sik Lee, Moon Gyu Lee, Yong Ki Min, Jong Hyun Kim, Eun Young Oh, Yun Jae Chung, Sang Soo Bae; J Korean Endocr Soc. 1998;13(3):432-438. Published online January 1, 2001

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Abstract PDF: Goiter is present in 25-50% of patients with acromegaly, which probably results from IGF- I stimulation of thyroid cell growth. These goiters are usually non-toxic but there have been well documented cases of co-existent hyperthyroidism and acromegaly. Graves disease with acromegaly has been rarely reported compared with the other type of hyperthyroidism due to increased tumoral secretion of TSH. We experienced a 44-year-old woman who presented with Graves disease and acromegaly. Basal serum GH and IGF-I concentrations were 10.8 pg/L and 571.82 ng/mL, respectively (reference value: (5 mg/L and 130-354 ng/mL, respectively). GH was not suppressed less than 2 pg/L during oral glucose loading test. GH was stimulated by TRH. Postcontrast sellar MRI demonstrated ovoid-shaped low signal intensity nodule measuring O.8 cm in diameter in left side of pituitary gland. Thyroid scan(131I) showed enlarged thyroid with increased radioiodine uptake (61.3%). Histologic examination showed acidophilic adenoma. GH and prolactin were positive on immunohistochemical staining. GH was suppressed less than 2.26 mg/L by oral glucose loading following operation. The patient has been followed with antithyroid drug(PTU) medication after operation(TSA).

A Case of Ocular Myasthenia Associated with Graves's disease.: Hong Nam Kim, Keum Jin Ban, Seok Shi, Shin Han, Soo Jin Yoon, So Yeon Kim, Byoung Ik Park, Kwon Jun Lee; J Korean Endocr Soc. 1998;13(2):252-257. Published online January 1, 2001

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Abstract PDF: The occurrences of thyrotoxicosis in patients with myasthenia gravis have been reported before the knowledge of the pathogenesis of the two disease. Thytotoxicosis is known to occur in 3 to 6 percent of patients with myasthenia gravis and myasthenia gravis occurs in only a fraction of 1 percent of the thyrotoxic populatian. Myasthenia gravis is currently considered as a systemic autoimmune disorder of acetylcholine receptor and often presented with other autoimmune diseases such as SLE, Rheumatoid arthritis. We experienced a 18-year-old woman who presented with graves disease and isolated ocular myasthenia gravis. Chest CT didnot reveal enlarged thymus. The usual treatement of myasthenia gravis associated with thymtoxicosis consists of medical control of the thyrotoxicosis, then thymectomy and later subtotal thyroidectomy. Her ptosis and thyrotoxicosis have improved after the medicatian of anticholinesterase and propylthiourecil. A case of ocular myasthenia gravis with Gravesdisease was experienced, so we reported the case with a brief review of literature.

A Case of Systemic Lupus Erythematous (SLE) with Graves' Desease and Idiopathic Thrombocytopenic Purpura (ITP).: In Sung Cho, Kang Seo Park, Young Cheol Kim, Kyung Il Chun, Sook Kyung Hong, Hyun Choi, Jae Ryong Han; J Korean Endocr Soc. 1997;12(4):677-683. Published online January 1, 2001

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Abstract PDF: Autoimmune diseases are occasionally associated with other autoimmune diseases in the same patients. Autoimmune Graves' disease has been associated with systemic rheumatic diseases including systemic lupus erythematosus (SLE). And Graves' disease associated with idiopathic thrornbocytopenic purpura (ITP) has been reported many times in Korea. There is a special relationship between SLE and ITP, both of which are autoimmune diseases. Some patients with thrombocytopenic purpura, labeled as idiopathic at the onset, later develop a classical course of SLE, suggesting that ITP may be an early manifestation of SLE. The relationships among these three conditions and their pathogenesis are poorly undemtood, and the coexistence of these diseases at the same time has been reported very rarely, but it may be very probable that there are some relationships among them. We report a case of SLE associated with Graves' disease and ITP treated well by imunosup-pressive agent who had been suffering from recurrence by conventional treatments (antithyroid medication, corticosteroid, subtotal thyroidectomy and splenectomy).

A Case of Graves' Disease Associated with Guillain-Barre Syndrome.: Ji Hyun Lee, Ki Sung Ahn, Sang Chae Lee, Jung Dong Bae, Yong Bum Park, Soo Mi Keum, Jin Hyung Park, Jong Won Choi, Ji Yong Choi, Sung Kook Jang, Ho Sang Son; J Korean Endocr Soc. 1997;12(4):614-620. Published online January 1, 2001

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Abstract PDF: Graves disease, an autoimmune endocrine disorder, which causes defects in cellular and humoral immunity, is associated with insulin-dependent diabetes mellitus, Addisons disease, pemicious anemia, and rheumatoid arthritis. Graves disease is associated with various neuro-muscular disorders, such as myopathy, exophalmous oculopathy, periodic paralysis, myastenia gravis and rarely Guillain-Barre syndrome. Guillain-Barre syndrome is considered as an autoimmune disease which can occur concurrently with other autoimmune disorders. This syndrome is characterized by segmental demyelination and axonal degeneration in electrophysiology due to autoantibody to nervous systems via cellular and humoral autoimmunity. In Graves disease, the exact mechanism of the associated Guillain-Barre syndrome is not well understood but it is considered that the autoimmunity is the leading cause of development of both diseases. A 37 year-old man had suffered from thyrotoxic symptoms and progressive symmetrical muscular paralysis. In nerve conduction velocity studies, the result shows peripheral neuropathy; axonopathy; myelinopathy; motor nerve and sensory nerve derangement; right first sacral nerve neuropathy; and decreased CMAP amplitude. The patient was treated with propylthiouracil and high dose intravenous immunoglobulin (400mg/kg/day for Sdays). He responded to the therapy well and became euthyroid state with improvement of muscle weakness. We report a case of Graves' disease associated with Guillain-Barre syndrome with brief review of literature which shows a possible relationship between both diseases.

Original Articles

Anticardiolipin Antibody in Graves' Disease.: Young Ki Song, Ki Soo Kim, Jung Hee Lee; J Korean Endocr Soc. 1997;12(4):528-532. Published online January 1, 2001

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Abstract PDF: BACKGROUND
S: Antiphospholipid antibodies which are frquently found in systemic lupus erythematosus and primary antiphospholipid syndrome are associated with recurrent abortions and thromboembolism. In this study the authors investigated whether antiphospholipid antibodies are found in Graves disease, a representative organ-specific autoimmune disease and what is the clinical implication of the antiphospholipid antibodies if they appear in Graves disease. METHODS: Anticardiolipin antibody and lupus anticoagulant activity were measured in 57 untreated hyperthyroid Graves patients. 42 euthyroid patients with thyroid nodules served as controls. RESULTS: Eight of the 57 patients with Graves disease had anticardiolipin antibody which was significantly more frequent than in control group. Six of the eight patients who had anticardiolipin antibody had IgM type antibody and two had IgG type antibody. All their antibody activity declined with several months of antithyroid drug therapy and finally disappeared when the patients became euthyroid. Presence of anticardiolipin antibody had no relationship with clinical events such as spontaneous abrtion and thromboembolism. CONCLUSION: Anticardiolipin antibody is frequently found in patients with Graves disease. They seem to appear as an epiphenomenon of autoimmunity and they seem not to have any clinical implications.

Changes in Properties of Thyrotropin Receptor Antibodies Following Radioiodine Treatment in Patients with Graves' Disease.: Won Bae Kim, Hyun Kyung Chung, Bo Youn Cho, Hong Kyu Lee, Chang Soon Koh, Do Joon Park, Yeon Sahng Oh; J Korean Endocr Soc. 1997;12(2):194-206. Published online January 1, 2001

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Abstract PDF: BACKGROUND
It has been suggested that thyroid stimulation blocking antibody (TSBAb) is involved in the development of early hypothyroidism after radioiodine treatment in patient with Graves disease. However, previous studies have reported the effect of radioiodine treatment on overall changes of TSH receptor antibodies without detailed observation of changes in properties of TSH receptor antibodies. The aim of this study is to evaluate the effect of radioiodine treatment on thyroid stimulation antibody (TSAb) or on thyroid stimulation blocking antibody (TSBAb) activities and to see whether the appearance of TSBAb after radioiodine treatment is involved in the development of early hypothyroidism in patients with Graves disease. METHODS: The activities of TSAb, TSBAb were measured serially with human TSH receptor transfected Chinese hamster ovary (CHO) cells in 36 patients with Graves disease who received 131I treatment. In addition to the wild type TSH receptor-expressing cells, we used a chimeric receptor that 90-165 amino acid residues were substituted by those of rat LH/CG receptor (Mc2) for measurement of TSBAb without interference by the presence of TSAb and for evaluation of TSAb epitope spreading. We evaluated the association of early hypothyroidism after 131I treatment with changes of various immunologic parameters. RESULTS: In 14 (39%) of 36 patients, TSBAb activities were present in their sera before or after 131I treatment. Four of them had TSBAb activities before 131 treatment, and 12 newly acquired TSBAb activities after 131I treatment. The existence of TSBAb was not associated with the development of early hypothyroidism after 131I treatment but with low TSAb activities before 131 treatment, high thyroidal uptake of 131I given and with old age. The phenomena of epitope spreading measured by TSAb with Mc2 mutant clone before and after 131I treatment was not infrequent, but it had no clinical relevance. CONCLUSION: These results suggest that the existence of TSBAb may be not a major factor in the development of early hypothyroidism after radioiodine treatment in Graves disease. Other factors such as TSAb activities before radioiodine treatment, the efficiency of thyroidal uptake of 131I or old age are associated with the development of early hypothyroidism.

Case Report

Ensulin Autoimmune Syndrome in a Patient with Methimazole-Treated Graves' Disease: A Case report.: Joong Kyu Lim, Yong An Woo, Sung Jin Kang, Sung Sik Yoo, Kun Young Hong, Soon Ho Kim; J Korean Endocr Soc. 1998;13(4):612-616. Published online January 1, 2001

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Abstract PDF: Insulin autoimmune syndrome (IAS) includes fasting or reactive hypoglycemia, hyperinsulinemia and the presence of insulin-binding antibodies in patients who have never been exposed to exogenous insulin. This report concems a 29-year-old male patient with Graves disease who had history of having taken methimazole for two months, without any consequence, 6 months previously. However, when methimazole was administered again for three weeks, the patient suffered hypoglycemia during the next fourth week. He denied history of diabetes mellitus (DM), of taking any oral hypoglycemic agent or of having received insulin injection. Laboratory data showed total serum insulin level > 300 pu/mL, C-peptide reactivity (CPR) 8.0ng/mL and insulin antibody 89%. After stopping methimazole, he was treated with radioiodine (131I). There was no episode of hypoglycemic attack during 8 months of follow-up.

Original Article

Antibody-dependent Cell-mediated Cytotoxitity as a Prognostic Indicator in the Medical Treatment of Graves' Disease.: Kwan Woo Lee, Young Goo Shin, Hye Rim Ro, Sung Kyu Lee, Yun Suk Chung, Hyun Man Kim, Yoon Jung Kim, Eun Kyung Hong, Bong Nam Chae; J Korean Endocr Soc. 1998;13(4):554-562. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The several forms of treatment of Graves disease-thyroidectomy, antithyroid drugs and radioiodide therapy-are in wide use now. But which therapy is best is a matter of debate. Some authors reported that in patients who underwent thyroidectomy, higher titers of serum antimicrosomal antibody were associated with 1) higher formation rates of germinal centers, 2) more lymphocyte infiltration in the thyroid tissue, 3) higher incidence of hypothyroidism, and 4) lower incidence of recurrence. We were interested in the relationship of thyroid autoantibody titers, ADCC(antibody-dependent cell-mediated cytotoxicity) activity and the clinical response to antithyroid medication. METHODS: We measured ADCC activities from patients in Graves disease(n-48), Hashimoto thyroiditis(n=17) and normal control(n=9). The patients of Graves disease were followed up for more than 1 year, and they were grouped into A(n=17, well responsed group to antithyroid medication) and B(n=31, poorly responsed group). We examined ADCC activities of patients' sera by chromium release assay. RESULTS: 1) Mean age of patients with Graves disease was 34.4210.4 years and 15 patients were male(31%). 2) Results of thyroid function tests of the Graves' patients were T 585.9 +/- 255.3 ng/dL, T4 21.3 +/- 12.2 mg/dL, TSH 0.11 +/- 0.06mIU/mL. Concentrations of antimicrosomal antibody, antithyroglobulin antibody and thyrotropin binding inhibitory immunoglobulin were 1279.1 +/- 1486.7 IU/mL, 488.1 +/- 751.1 IU/mL, and 38.5 +/- 33.4U/L respectively. 3) There was no significant difference between levels of thyroid hormones or concentrations of thyroid autoantibodies and ADCC activities in graves patients. 4) The ADCC activity of the Graves patient group(24.49%) was significantly higher than that of the normal control group(3.76%), and significantly lower than that of the Hashimotos thyroiditis group(36.34%). 5) There was no significant difference in ADCC activity between group A(18.24 +/- 13.44%) and B(27.91 +20.02%). CONCLUSION: From this results, we suggested that ADCC activity seems to be no value as a prognostic factor in predicting the response to antithyroid drugs in Graves disease patients. But, further studies, larger number of patients and long-term follow up, are needed.

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