Endocrinology and Metabolism

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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Abstract PDF PubReader ePub: 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.

Original Articles

Thyroid
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; Endocrinol Metab. 2024;39(4):579-589. Published online May 23, 2024; DOI: https://doi.org/10.3803/EnM.2024.1918

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Abstract PDF Supplementary Material PubReader ePub: Background
Changes in thyrotropin receptor antibody (TRAb) levels are associated with the clinical outcomes of Graves’ hyperthyroidism. However, the effects of the patterns of TRAb changes on patient prognosis according to the treatment duration of antithyroid drugs (ATDs) are not well established.
Methods
In this retrospective cohort study, 1,235 patients with Graves’ hyperthyroidism who were treated with ATDs for more than 12 months were included. Patients were divided into two groups according to treatment duration: group 1 (12–24 months) and group 2 (>24 months). Risk prediction models comprising age, sex, and either TRAb levels at ATD withdrawal (model A) or patterns of TRAb changes (model B) were compared.
Results
The median treatment duration in groups 1 (n=667, 54%) and 2 (n=568, 46%) was 17.3 and 37.1 months, respectively. The recurrence rate was significantly higher in group 2 (47.9%) than in group 1 (41.4%, P=0.025). Group 2 had significantly more goiter, thyroid eye disease, and fluctuating and smoldering type of TRAb pattern compared with group 1 (all P<0.001). The patterns of TRAb changes were an independent risk factor for recurrence after adjusting for other confounding factors in all patients, except in group 1. Integrated discrimination improvement and net reclassification improvement analyses showed that model B performed better than model A in all patients, except in group 1.
Conclusion
The dynamic risk model, including the patterns of TRAb changes, was more suitable for predicting prognosis in patients with Graves’ hyperthyroidism who underwent longer ATD treatment duration.

Hypothalamus and pituitary gland
Clinical Characteristics, Diagnosis, and Treatment of Thyroid Stimulating Hormone-Secreting Pituitary Neuroendocrine Tumor (TSH PitNET): A Single-Center Experience: Jung Heo, Yeon-Lim Suh, Se Hoon Kim, Doo-Sik Kong, Do-Hyun Nam, Won-Jae Lee, Sung Tae Kim, Sang Duk Hong, Sujin Ryu, You-Bin Lee, Gyuri Kim, Sang-Man Jin, Jae Hyeon Kim, Kyu Yeon Hur; Endocrinol Metab. 2024;39(2):387-396. Published online February 5, 2024; DOI: https://doi.org/10.3803/EnM.2023.1877

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Background
Thyroid-stimulating hormone (TSH)-secreting pituitary neuroendocrine tumor (TSH PitNET) is a rare subtype of PitNET. We investigated the comprehensive characteristics and outcomes of TSH PitNET cases from a single medical center. Also, we compared diagnostic methods to determine which showed superior sensitivity.
Methods
A total of 17 patients diagnosed with TSH PitNET after surgery between 2002 and 2022 in Samsung Medical Center was retrospectively reviewed. Data on comprehensive characteristics and treatment outcomes were collected. The sensitivities of diagnostic methods were compared.
Results
Seven were male (41%), and the median age at diagnosis was 42 years (range, 21 to 65); the median follow-up duration was 37.4 months. The most common (59%) initial presentation was hyperthyroidism-related symptoms. Hormonal co-secretion was present in four (23%) patients. Elevated serum alpha-subunit (α-SU) showed the greatest diagnostic sensitivity (91%), followed by blunted response at thyrotropin-releasing hormone (TRH) stimulation (80%) and elevated sex hormone binding globulin (63%). Fourteen (82%) patients had macroadenoma, and a specimen of one patient with heavy calcification was negative for TSH. Among 15 patients who were followed up for more than 6 months, 10 (67%) achieved hormonal and structural remission within 6 months postoperatively. A case of growth hormone (GH)/TSH/prolactin (PRL) co-secreting mixed gangliocytoma-pituitary adenoma (MGPA) was discovered.
Conclusion
The majority of the TSH PitNET cases was macroadenoma, and 23% showed hormone co-secretion. A rare case of GH/TSH/PRL co-secreting MGPA was discovered. Serum α-SU and TRH stimulation tests showed great diagnostic sensitivity. Careful consideration is needed in diagnosing TSH PitNET. Achieving remission requires complete tumor resection. In case of nonremission, radiotherapy or medical therapy can improve the long-term remission rate.

Citations

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TSH-secreting pituitary adenomas and bone
Marco Losa, Alberto Vassallo, Stefano Frara, Pietro Mortini, Andrea Giustina
Pituitary.2024; 27(6): 752. CrossRef

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

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

Citations

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Long-term Effect of Thyrotropin-binding Inhibitor Immunoglobulin on Atrial Fibrillation in Euthyroid Patients
Jung-Chi Hsu, Kang-Chih Fan, Ting-Chuan Wang, Shu-Lin Chuang, Ying-Ting Chao, Ting-Tse Lin, Kuan-Chih Huang, Lian-Yu Lin, Lung-Chun Lin
Endocrine Practice.2024; 30(6): 537. CrossRef
Treatment Patterns and Preferences for Graves’ Disease in Korea: Insights from a Nationwide Cohort Study
Kyeong Jin Kim, Jimi Choi, Soo Myoung Shin, Jung A Kim, Kyoung Jin Kim, Sin Gon Kim
Endocrinology and Metabolism.2024; 39(4): 659. CrossRef
Dynamic Risk Model for the Medical Treatment of Graves’ Hyperthyroidism according to Treatment Duration
Meihua Jin, Chae A Kim, Min Ji Jeon, Won Bae Kim, Tae Yong Kim, Won Gu Kim
Endocrinology and Metabolism.2024; 39(4): 579. CrossRef
Effect of COVID-19 Vaccination on Thyroid Disease in 7 Million Adult and 0.2 Million Adolescent Vaccine Recipients
Sungho Bea, Hwa Young Ahn, Jieun Woo, Ju-Young Shin, Sun Wook Cho
The Journal of Clinical Endocrinology & Metabolism.2024;[Epub] CrossRef
The Current Status of Hyperthyroidism in Korea
Hyemi Kwon
Endocrinology and Metabolism.2023; 38(4): 392. CrossRef
Is Thyroid Dysfunction Associated with Unruptured Intracranial Aneurysms? A Population-Based, Nested Case–Control Study from Korea
Hyeree Park, Sun Wook Cho, Sung Ho Lee, Kangmin Kim, Hyun-Seung Kang, Jeong Eun Kim, Aesun Shin, Won-Sang Cho
Thyroid®.2023; 33(12): 1483. CrossRef

Thyroid
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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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
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.2024;[Epub] CrossRef

Review Article

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

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

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Diagnosis and therapeutic approach to bone health in patients with hypopituitarism
Justyna Kuliczkowska-Płaksej, Aleksandra Zdrojowy-Wełna, Aleksandra Jawiarczyk-Przybyłowska, Łukasz Gojny, Marek Bolanowski
Reviews in Endocrine and Metabolic Disorders.2024; 25(3): 513. CrossRef
Osteoporosis, Osteoarthritis, and Subchondral Insufficiency Fracture: Recent Insights
Shunichi Yokota, Hotaka Ishizu, Takuji Miyazaki, Daisuke Takahashi, Norimasa Iwasaki, Tomohiro Shimizu
Biomedicines.2024; 12(4): 843. CrossRef
Acute hypercalcemic crisis: A narrative review with a focus on pregnancy
Nadia Sabbah
Annales d'Endocrinologie.2024; 85(6): 604. CrossRef
Increased risk of malignancy and osteoporosis in primary Sjögren’s syndrome with thyroid diseases: potential implication from T cells
Xiaomeng Cui, Jun Li, Yizhen Sang, Wei Liu, Yikang Lu, Wei Li, Li Ma, Xinying Liu
Rheumatology.2024;[Epub] CrossRef
Review on the protective activity of osthole against the pathogenesis of osteoporosis
Jincai Chen, Xiaofei Liao, Juwen Gan
Frontiers in Pharmacology.2023;[Epub] CrossRef
Estudio comparativo tras la cirugía tiroidea y otras variables asociadas al desarrollo de osteoporosis en una cohorte latinoamericana
María Paula Ciliberti Artavia, Juan Sebastián Theran León, Jaime Alberto Gómez Ayala, Valentina Cabrera Peña, Rafael Guillermo Parales Strauch, Edgar Camilo Blanco Pimiento, Luis Andres Dulcey Sarmiento, Juan Camilo Martínez, Juan Camilo Mayorca, María Al
Revista Salud y Desarrollo.2023; 7(2): e605. CrossRef

Original Articles

Thyroid
Efficacy and Safety of Long-Term Methimazole versus Radioactive Iodine in the Treatment of Toxic Multinodular Goiter: Fereidoun Azizi, Navid Saadat, Mir Alireza Takyar, Hengameh Abdi, Ladan Mehran, Atieh Amouzegar; Endocrinol Metab. 2022;37(6):861-869. Published online November 23, 2022; DOI: https://doi.org/10.3803/EnM.2022.1476

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Background
This study compared the degree of sustained control of hyperthyroidism in patients with toxic multinodular goiter (TMNG) treated with long-term methimazole (LT-MMI) or radioactive iodine (RAI).
Methods
In this clinical trial, 130 untreated patients with TMNG were randomized to either LT-MMI or RAI treatment. Both groups were followed for 108 to 148 months, with median follow-up durations of 120 and 132 months in the LT-MMI and RAI groups, respectively. Both groups of patients were followed every 1 to 3 months in the first year and every 6 months thereafter.
Results
After excluding patients in whom the treatment modality was changed and those who were lost to follow-up, 53 patients in the LT-MMI group and 54 in the RAI group completed the study. At the end of the study period, 50 (96%) and 25 (46%) patients were euthyroid, and two (4%) and 25 (46%) were hypothyroid in LT-MMI and RAI groups, respectively. In the RAI group, four (8%) patients had subclinical hyperthyroidism. The mean time to euthyroidism was 4.3±1.3 months in LT-MMI patients and 16.3± 15.0 months in RAI recipients (P<0.001). Patients treated with LT-MMI spent 95.8%±5.9% of the 12-year study period in a euthyroid state, whereas this proportion was 72.4%±14.8% in the RAI-treated patients (P<0.001). No major treatment-related adverse events were observed in either group.
Conclusion
In patients with TMNG, LT-MMI therapy is superior to RAI treatment, as shown by the earlier achievement of euthyroidism and the longer duration of sustained normal serum thyrotropin.

Citations

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Control rate of hyperthyroidism and its associated factors after prolonged use of anti-thyroid drugs in a hospital setting, Northwest Ethiopia
Seyoum Mengesha, Abilo Tadesse, Biruk Mulat Worku, Kifle Alamrew, Tesfaye Yesuf, Yonas Gedamu
Medicine.2024; 103(23): e38201. CrossRef
Approach to the Patient Considering Long-term Antithyroid Drug Therapy for Graves’ Disease
Fereidoun Azizi, Ladan Mehran, Hengameh Abdi, Atieh Amouzegar
The Journal of Clinical Endocrinology & Metabolism.2024; 109(10): e1881. CrossRef
Mechanism of Huatan Sanjie Fang in improving goiter in Graves' disease mice based on the Hippo signaling pathway
Huimin Yuan, Wenxin Ma, Yifei Song, Hang Wang, Shuxin Yan, Silan Hao, Xiaoyun Zhu, Yang Tang
Journal of Traditional Chinese Medical Sciences.2023; 10(3): 289. 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.

Citations

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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 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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Nadia Sawicka-Gutaj, Dawid Gruszczyński, Natalia Zawalna, Kacper Nijakowski, Agnieszka Skiba, Mateusz Pochylski, Jerzy Sowiński, Marek Ruchała
Pharmacological Reports.2024; 76(1): 185. CrossRef
Increased risk of diabetes mellitus and hyperlipidemia in patients with differentiated thyroid cancer
Hwa Young Ahn, Jooyoung Lee, Jinmo Kang, Eun Kyung Lee
European Journal of Endocrinology.2024; 190(3): 248. CrossRef
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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®.2024;[Epub] CrossRef
Prevalencia de diabetes en personas con disfunción tiroidea
Juan J. Díez, Pedro Iglesias
Medicina Clínica.2023; 160(8): 333. CrossRef
Control of Thyroid Dysfunction in Spanish Population Registered in the Primary Care Clinical Database: An Analysis of the Proportion of Patients with Thyrotropin Values Outside the Reference Range
Juan J. Díez, Pedro Iglesias
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Prevalence of thyroid dysfunction and its relationship to income level and employment status: a nationwide population-based study in Spain
Juan J. Díez, Pedro Iglesias
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Prevalence of diabetes in people with thyroid dysfunction
Juan J. Díez, Pedro Iglesias
Medicina Clínica (English Edition).2023; 160(8): 333. CrossRef
Diabetes Mellitus Secondary to Endocrine Diseases: An Update of Diagnostic and Treatment Particularities
Mihaela Simona Popoviciu, Lorena Paduraru, Raluca Marinela Nutas, Alexandra Maria Ujoc, Galal Yahya, Kamel Metwally, Simona Cavalu
International Journal of Molecular Sciences.2023; 24(16): 12676. CrossRef
Thyroid Eye Disease and Its Association With Diabetes Mellitus: A Major Review
Roshmi Gupta, Pramila Kalra, Lakshmi B. Ramamurthy, Suryasnata Rath
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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
Endocrinology and Metabolism.2022; 37(6): 891. CrossRef
Diabetes and Hyperthyroidism: Is There a Causal Link?
Sang Yong Kim
Endocrinology and Metabolism.2021; 36(6): 1175. CrossRef

Brief Report

Thyroid
Outcomes and Predictors of 30-Day Readmissions for Hyperthyroidism: A Nationwide Study: Michael Salim, Zain El-amir, Asim Kichloo, Farah Wani, Ehizogie Edigin, Hafeez Shaka; Endocrinol Metab. 2021;36(6):1307-1311. Published online December 1, 2021; DOI: https://doi.org/10.3803/EnM.2021.1190

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Hyperthyroidism is associated with an elevated risk of cardiovascular events and worse hospital outcomes. The Nationwide Readmissions Database (NRD) 2018 was used to determine the characteristics of 30-day readmission in patients with hyperthyroidism. The 30-day all-cause readmission rate for hyperthyroidism was 10.3%. About 21.7% had hyperthyroidism as the principal diagnosis on readmission. Readmissions were associated with an increased odds of inpatient mortality (odds ratio, 7.04; 95% confidence interval [CI], 3.97 to 12.49), length of stay (5.2 days vs. 4.0 days; 95% CI, 0.7 to 1.8), total hospital charges, and cost of hospitalizations. Independent predictors of 30-day all-cause readmissions included Charlson Comorbidity Index ≥3 (adjusted hazard ratio [aHR], 1.76; 95% CI, 1.15 to 2.71), discharge against medical advice (aHR, 2.30; 95% CI, 1.50 to 3.53), protein-energy malnutrition (aHR, 1.54; 95% CI, 1.15 to 2.07), and atrial fibrillation (aHR, 1.41; 95% CI, 1.11 to 1.79). Aggressive but appropriate monitoring is warranted in patients with hyperthyroidism to prevent readmissions.

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Burden of In-Hospital Admissions and Outcomes of Thoracic Outlet Compression Syndrome in the United States From 2010 to 2021
Fidelis E Uwumiro, Oluwatoyin Ayo-Farai, Emmanuel O Uduigwome, Stafford Nwebonyi, Emmanuel S Amadi, Oluwatobi A Faniyi, Ihunanya Kanu, Emmanuel A Babawale, Gloria Alufohai, Chukwuebuka Aguchibe, Ifeanyi Agu
Cureus.2024;[Epub] CrossRef

Original Articles

Clinical Study
The Association of Overt and Subclinical Hyperthyroidism with the Risk of Cardiovascular Events and Cardiovascular Mortality: Meta-Analysis and Systematic Review of Cohort Studies: Seo Young Sohn, Eunyoung Lee, Min Kyung Lee, Jae Hyuk Lee; Endocrinol Metab. 2020;35(4):786-800. Published online November 25, 2020; DOI: https://doi.org/10.3803/EnM.2020.728

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Background
Whether hyperthyroidism is an independent risk factor for cardiovascular events remains controversial. We aimed to evaluate the association of overt and subclinical hyperthyroidism with the risk of ischemic heart disease (IHD), stroke, heart failure, and cardiovascular mortality.
Methods
Studies regarding the association between hyperthyroidism and cardiovascular events were searched on PubMed and Embase databases. The cardiovascular disease (CVD) risk was classified as high and low, based on pre-existing diseases, including history of coronary, cerebral, or peripheral artery disease; heart failure; atrial fibrillation; diabetes mellitus; or chronic kidney disease.
Results
Thirty-seven cohort studies were included in this meta-analysis. The pooled hazard ratio for subjects with overt hyperthyroidism compared with the control group was 1.11 (95% confidence interval [CI], 1.03 to 1.19) for IHD, 1.35 (95% CI, 1.03 to 1.75) for stroke, and 1.20 (95% CI, 1.00 to 1.46) for cardiovascular mortality. For subjects with subclinical hyperthyroidism, the pooled hazard ratio was 1.24 (95% CI, 1.07 to 1.45) for IHD, when compared with the control group. Subgroup analysis by CVD risk showed that the risk of stroke in overt hyperthyroidism was increased in the low CVD risk group; however, these association was not observed in the high CVD risk group. Similarly, the risk of IHD in subjects with subclinical hyperthyroidism was significantly increased in the low CVD risk group.
Conclusion
Overt hyperthyroidism is associated with increased risk of IHD, stroke, and cardiovascular mortality, and subclinical hyperthyroidism is associated with increased risk of IHD. These associations were particularly observed in the low risk CVD group without underlying CVD.

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Atrial Fibrillation in Patients with Hyperthyroidism.: Ju Yong Lee, Chang Ho Song, Byeung Su Yu, Choon Hee Chung, Yoon Sok Chung, Hyeon Man Kim; J Korean Endocr Soc. 1995;10(1):52-57. Published online November 6, 2019

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Abstract PDF: Hyperthyroidism is a well known cause of atrial fibrillation. It is also known that control of hyperthyroidism can usually curb thyrotoxic atrial fibrillation and restore sinus rhythm. In this study, 282 patients with hyperthyroidism were investigated to quantify the incidence of atrial fibrillation, and to identify the vulnerable groups. In addition, we compared two groups of subjects with atrial fibrillation-one group with hyperthyroidism and the other group without - to study their reversion rate to sinus rhythm. Lastly, we investigated the factors affecting reversion to sinus rhythm in patients with thyrotoxic atrial fibrillation.The results were follows;1) Among 282 patients with hyperthyroidism, 35 cases(12.4%) had atrial fibrillation. Atrial fibrillations were more prevalent among male patient(19.4%) and elderly patients(42.9%) than female patients(10.0%) and young patients(10.0%).2) Reversion to normal sinus rhythm in patients with thyrotoxic atrial fibrillation(39.3%) was significantly higher than that in patients without hyperthyroidism(17.4%, p<0.001).3) Reversion to normal sinus rhythm was achieved within 28 weeks from the beginnig of antithyroid treatment in patients with thyrotoxic atrial fibrillation. Although there were no significant differences in mean age, sex ratio, and initial and follow-up thyroid hormone levels between the reversion group and non-reversion group, associated heart diseases were more prevalent in the latter group(18.2% vs. 47.1%).It can be concluded that thyrotoxic atrial fibrillations were more common in male patient and elderly patient groups, and could be frequently reverted to normal sinus rhythm by antithyroid treatment. We also suggest that the duration of artrial fibrillation(from intial onset of the condition), and associated heart diseases, may be important predictive factors for the reversion of atrial fibrillation in patients with hyperthyroidism.

Review Articles

Thyroid
Digital Medicine in Thyroidology: A New Era of Managing Thyroid Disease: Jae Hoon Moon, Steven R. Steinhubl; Endocrinol Metab. 2019;34(2):124-131. Published online June 24, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.2.124

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Digital medicine has the capacity to affect all aspects of medicine, including disease prediction, prevention, diagnosis, treatment, and post-treatment management. In the field of thyroidology, researchers are also investigating potential applications of digital technology for the thyroid disease. Recent studies using artificial intelligence (AI)/machine learning (ML) have reported reasonable performance for the classification of thyroid nodules based on ultrasonographic (US) images. AI/ML-based methods have also shown good diagnostic accuracy for distinguishing between benign and malignant thyroid lesions based on cytopathologic findings. Assistance from AI/ML methods could overcome the limitations of conventional thyroid US and fine-needle aspiration cytology. A web-based database has been developed for thyroid cancer care. In addition to its role as a nationwide registry of thyroid cancer, it is expected to serve as a clinical platform to facilitate better thyroid cancer care and as a research platform providing comprehensive disease-specific big data. Evidence has been found that biosignal monitoring with wearable devices may predict thyroid dysfunction. This real-world thyroid function monitoring could aid in the management and early detection of thyroid dysfunction. In the thyroidology field, research involving the range of digital medicine technologies and their clinical applications is expected to be even more active in the future.

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Thyroid
Graves' Disease: Can It Be Cured?: Wilmar M. Wiersinga; Endocrinol Metab. 2019;34(1):29-38. Published online March 21, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.1.29

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Whether or not Graves' hyperthyroidism can be really cured, depends on the definition of “cure.” If eradication of thyroid hormone excess suffices for the label “cure,” then all patients can be cured because total thyroidectomy or high doses of ¹³¹I will abolish hyperthyroidism albeit at the expense of creating another disease (hypothyroidism) requiring lifelong medication with levothyroxine. I would not call this a “cure,” which I would like to define as a state with stable thyroid stimulating hormone (TSH), free thyroxine, and triiodothyronine serum concentrations in the normal range in the absence of any thyroid medication. Surgery and radioiodine are unlikely to result in so-defined cures, as their preferable aim as stated in guidelines is to cause permanent hypothyroidism. Discontinuation of antithyroid drugs is followed by 50% recurrences within 4 years; before starting therapy the risk of recurrences can be estimated with the Graves' Recurrent Events After Therapy (GREAT) score. At 20-year follow-up about 62% had developed recurrent hyperthyroidism, 8% had subclinical hypothyroidism, and 3% overt hypothyroidism related to TSH receptor blocking antibodies and thyroid peroxidase antibodies. Only 27% was in remission, and might be considered cured. If the definition of “cure” would also include the disappearance of thyroid antibodies in serum, the proportion of cured patients would become even lower.

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Original Article

Thyroid
Prevalence and Annual Incidence of Thyroid Disease in Korea from 2006 to 2015: A Nationwide Population-Based Cohort Study: Hyemi Kwon, Jin-hyung Jung, Kyung-Do Han, Yong-Gyu Park, Jung-Hwan Cho, Da Young Lee, Ji Min Han, Se Eun Park, Eun-Jung Rhee, Won-Young Lee; Endocrinol Metab. 2018;33(2):260-267. Published online June 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.2.260

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Background

The incidence of thyroid nodules has increased worldwide in recent years. Thyroid dysfunction is a potential risk factor for hypercholesterolemia, cardiovascular disease, osteoporosis, arrhythmia, and neuropsychiatric disease. This study investigated the prevalence and annual incidence of thyroid nodules, hypothyroidism, and hyperthyroidism in Koreans.

Methods

In this nationwide population-based cohort study, 51,834,660 subjects were included using the National Health Information database from 2006 to 2015, after the exclusion of subjects with thyroid cancer.

Results

The prevalence in Korea in 2015 of thyroid nodules, hypothyroidism in patients taking thyroid hormone, and hyperthyroidism in patients undergoing treatment was 15.82/1,000 population, 15.94/1,000 population, and 2.76/1,000 population, respectively. All these diseases were more prevalent among women than among men. The number of incident cases of these three thyroid diseases steadily increased from 2006 to 2012, and then decreased through 2015. The incidence of thyroid nodules, hypothyroidism treated with thyroid hormone, and treated hyperthyroidism was 6.79/1,000 population, 1.76/1,000 population, and 0.55/1,000 population, respectively, in Korea in 2015. The use of methimazole continuously increased, from 33% of total antithyroid drug prescriptions in 2006 to 74.4% in 2015, and it became the most frequently prescribed antithyroid drug in Korea. In contrast, the use of propylthiouracil continuously decreased.

Conclusion

This was the first nationwide study of the prevalence and annual incidence of thyroid nodules, hypothyroidism, and hyperthyroidism to take into account recent changes and to include the current status of patients receiving treatment.

Citations

Citations to this article as recorded by

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