Endocrinology and Metabolism

Volume 36(3); June 2021

Review Articles

Diabetes, Obesity and Metabolism
Recent Advances in Understanding Peripheral Taste Decoding I: 2010 to 2020: Jea Hwa Jang, Obin Kwon, Seok Jun Moon, Yong Taek Jeong; Endocrinol Metab. 2021;36(3):469-477. Published online June 18, 2021; DOI: https://doi.org/10.3803/EnM.2021.302

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Taste sensation is the gatekeeper for direct decisions on feeding behavior and evaluating the quality of food. Nutritious and beneficial substances such as sugars and amino acids are represented by sweet and umami tastes, respectively, whereas noxious substances and toxins by bitter or sour tastes. Essential electrolytes including Na⁺ and other ions are recognized by the salty taste. Gustatory information is initially generated by taste buds in the oral cavity, projected into the central nervous system, and finally processed to provide input signals for food recognition, regulation of metabolism and physiology, and higher-order brain functions such as learning and memory, emotion, and reward. Therefore, understanding the peripheral taste system is fundamental for the development of technologies to regulate the endocrine system and improve whole-body metabolism. In this review article, we introduce previous widely-accepted views on the physiology and genetics of peripheral taste cells and primary gustatory neurons, and discuss key findings from the past decade that have raised novel questions or solved previously raised questions.

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Physiology of the tongue with emphasis on taste transduction
Máire E. Doyle, Hasitha U. Premathilake, Qin Yao, Caio H. Mazucanti, Josephine M. Egan
Physiological Reviews.2023; 103(2): 1193. CrossRef
Polycystic kidney disease 2-like 1 channel contributes to the bitter aftertaste perception of quinine
Takahiro Shimizu, Takuto Fujii, Keisuke Hanita, Ryo Shinozaki, Yusaku Takamura, Yoshiro Suzuki, Teppei Kageyama, Mizuki Kato, Hisao Nishijo, Makoto Tominaga, Hideki Sakai
Scientific Reports.2023;[Epub] CrossRef
Sweet Taste Preference: Relationships with Other Tastes, Liking for Sugary Foods and Exploratory Genome-Wide Association Analysis in Subjects with Metabolic Syndrome
Rebeca Fernández-Carrión, Jose V. Sorlí, Oscar Coltell, Eva C. Pascual, Carolina Ortega-Azorín, Rocío Barragán, Ignacio M. Giménez-Alba, Andrea Alvarez-Sala, Montserrat Fitó, Jose M. Ordovas, Dolores Corella
Biomedicines.2021; 10(1): 79. CrossRef

Diabetes, Obesity and Metabolism
Receptor-Mediated Muscle Homeostasis as a Target for Sarcopenia Therapeutics: Jong Hyeon Yoon, Ki-Sun Kwon; Endocrinol Metab. 2021;36(3):478-490. Published online June 28, 2021; DOI: https://doi.org/10.3803/EnM.2021.1081

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Sarcopenia is a disease characterized by age-related decline of skeletal muscle mass and function. The molecular mechanisms of the pathophysiology of sarcopenia form a complex network due to the involvement of multiple interconnected signaling pathways. Therefore, signaling receptors are major targets in pharmacological strategies in general. To provide a rationale for pharmacological interventions for sarcopenia, we herein describe several druggable signaling receptors based on their role in skeletal muscle homeostasis and changes in their activity with aging. A brief overview is presented of the efficacy of corresponding drug candidates under clinical trials. Strategies targeting the androgen receptor, vitamin D receptor, Insulin-like growth factor-1 receptor, and ghrelin receptor primarily focus on promoting anabolic action using natural ligands or mimetics. Strategies involving activin receptors and angiotensin receptors focus on inhibiting catabolic action. This review may help to select specific targets or combinations of targets in the future.

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Impact of Vitamin D Level on Sarcopenia in Elderly People: A Critical Review
Saniya Khan, Sunil Kumar, Sourya Acharya, Anil Wanjari
Journal of Health and Allied Sciences NU.2023;[Epub] CrossRef
Alverine citrate promotes myogenic differentiation and ameliorates muscle atrophy
Jong Hyeon Yoon, Seung-Min Lee, Younglang Lee, Min Ju Kim, Jae Won Yang, Jeong Yi Choi, Ju Yeon Kwak, Kwang-Pyo Lee, Yong Ryoul Yang, Ki-Sun Kwon
Biochemical and Biophysical Research Communications.2022; 586: 157. CrossRef
Adeno-associated virus-mediated expression of an inactive CaMKIIβ mutant enhances muscle mass and strength in mice
Takahiro Eguchi, Yuji Yamanashi
Biochemical and Biophysical Research Communications.2022; 589: 192. CrossRef
Gastric Mobility and Gastrointestinal Hormones in Older Patients with Sarcopenia
Hsien-Hao Huang, Tse-Yao Wang, Shan-Fan Yao, Pei-Ying Lin, Julia Chia-Yu Chang, Li-Ning Peng, Liang-Kung Chen, David Hung-Tsang Yen
Nutrients.2022; 14(9): 1897. CrossRef
Molecular Mechanisms Underlying Intensive Care Unit-Acquired Weakness and Sarcopenia
Marcela Kanova, Pavel Kohout
International Journal of Molecular Sciences.2022; 23(15): 8396. CrossRef

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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Выраженность окислительного стресса и энзиматическая активность нейтрофилов крови у пациентов с болезнью Грейвса в зависимости от компенсации гипертиреоза
М. А. Дудина, С. А. Догадин, А. А. Савченко, И. И. Гвоздев
Ateroscleroz.2023; 18(4): 411. CrossRef
Application of oral inorganic iodine in the treatment of Graves’ disease
Yixuan Huang, Yihang Xu, Murong Xu, Xiaotong Zhao, Mingwei Chen
Frontiers in Endocrinology.2023;[Epub] CrossRef
Sex-specific risk factors associated with graves’ orbitopathy in Korean patients with newly diagnosed graves’ disease
Jooyoung Lee, Jinmo Kang, Hwa Young Ahn, Jeong Kyu Lee
Eye.2023;[Epub] CrossRef
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
Endocrinology and Metabolism.2022; 37(2): 323. CrossRef
The chemiluminescent and enzymatic activity of blood neutrophils in patients with Graves' disease depending on hyperthyroidism compensation
M. A. Dudina, A. A. Savchenko, S. A. Dogadin, I. I. Gvozdev
Clinical and experimental thyroidology.2022; 18(1): 4. CrossRef
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
Endocrinology and Metabolism.2021; 36(6): 1277. CrossRef

Thyroid
Subclinical Hypothyroidism: Prevalence, Health Impact, and Treatment Landscape: Won Sang Yoo, Hyun Kyung Chung; Endocrinol Metab. 2021;36(3):500-513. Published online June 18, 2021; DOI: https://doi.org/10.3803/EnM.2021.1066

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Subclinical hypothyroidism (sHypo) is defined as normal serum free thyroid hormone levels coexisting with elevated serum thyroid-stimulating hormone (TSH) levels. sHypo is a common condition observed in clinical practice with several unique features. Its diagnosis should be based on an understanding of geographic and demographic differences in biochemical criteria versus a global reference range for TSH that is based on the 95% confidence interval of a healthy population. During the differential diagnosis, it is important to remember that a considerable proportion of sHypo cases are transient and reversible in nature; the focus is better placed on persistent or progressive forms, which mainly result from chronic autoimmune thyroiditis. Despite significant evidence documenting the health impacts of sHypo, the effects of levothyroxine treatment (LT4-Tx) in patients with sHypo remains controversial, especially in patients with grade 1 sHypo and older adults. Existing evidence suggests that it is reasonable to refrain from immediate LT4-Tx in most patients if they are closely monitored, except in women who are pregnant or in progressive cases. Future research is needed to further characterize the risks and benefits of LT4-Tx in different patient cohorts.

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Subclinical hypothyroidism, outcomes and management guidelines: a narrative review and update of recent literature
Bogumila Urgatz, Salman Razvi
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G. T. Makhkamova, Sh. T. Turdieva
Meditsinskiy sovet = Medical Council.2023; (1): 212. CrossRef
Diagnóstico y tratamiento del hipotiroidismo subclínico en adultos mayores
Debbie Noelia Tebanta Albán, Gabriel Aníbal Hugo Merino, María Valentina Muñoz Arteaga, Ariana Lisseth Vázquez López
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Comparison of Five Different Criteria for Diagnosis of Subclinical Hypothyroidism in a Large-Scale Chinese Population
Yan-song Zheng, Sheng-yong Dong, Yan Gong, Jia-hong Wang, Fei Wang, Qiang Zeng
Frontiers in Endocrinology.2022;[Epub] CrossRef
Subclinical Hypothyroidism and Cognitive Impairment
Jung-Min Pyun, Young Ho Park, SangYun Kim
Journal of Alzheimer's Disease.2022; 88(2): 757. CrossRef
Effect of Levothyroxine Supplementation on the Cardiac Morphology and Function in Patients With Subclinical Hypothyroidism: A Systematic Review and Meta-analysis
Xichang Wang, Haoyu Wang, Qiuxian Li, Ping Wang, Yumin Xing, Fan Zhang, Jiashu Li, Zhongyan Shan
The Journal of Clinical Endocrinology & Metabolism.2022; 107(9): 2674. CrossRef
Natural history of subclinical hypothyroidism and prognostic factors for the development of overt hypothyroidism: Tehran Thyroid Study (TTS)
A. Amouzegar, M. Dehghani, H. Abdi, L. Mehran, S. Masoumi, F. Azizi
Journal of Endocrinological Investigation.2022; 45(12): 2353. CrossRef
Retrospective cohort analysis comparing changes in blood glucose level and body composition according to changes in thyroid‐stimulating hormone level
Hyunah Kim, Da Young Jung, Seung‐Hwan Lee, Jae‐Hyoung Cho, Hyeon Woo Yim, Hun‐Sung Kim
Journal of Diabetes.2022; 14(9): 620. CrossRef
Long working hours and risk of hypothyroidism in healthy workers: A cohort study
Yesung Lee, Woncheol Lee, Hyoung-Ryoul Kim
Epidemiology and Health.2022; : e2022104. CrossRef

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

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

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Update on Management of Medullary Thyroid Carcinoma: Focus on Nuclear Medicine
Giorgio Treglia, Vittoria Rufini, Arnoldo Piccardo, Alessio Imperiale
Seminars in Nuclear Medicine.2023;[Epub] CrossRef
Cabozantinib, Vandetanib, Pralsetinib and Selpercatinib as Treatment for Progressed Medullary Thyroid Cancer with a Main Focus on Hypertension as Adverse Effect
Linnea Højer Wang, Markus Wehland, Petra M. Wise, Manfred Infanger, Daniela Grimm, Michael C. Kreissl
International Journal of Molecular Sciences.2023; 24(3): 2312. CrossRef
A proposed grading scheme for predicting recurrence in medullary thyroid cancer based on the Ki67 index and metastatic lymph node ratio
Pengfei Xu, Di Wu, Xuekui Liu
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Efficacy and Safety of [177Lu]Lu-DOTA-TATE in Adults with Inoperable or Metastatic Somatostatin Receptor-Positive Pheochromocytomas/Paragangliomas, Bronchial and Unknown Origin Neuroendocrine Tumors, and Medullary Thyroid Carcinoma: A Systematic Literatur
Marianna Hertelendi, Oulaya Belguenani, Azzeddine Cherfi, Ilya Folitar, Gabor Kollar, Berna Degirmenci Polack
Biomedicines.2023; 11(4): 1024. CrossRef
Pralsetinib: chemical and therapeutic development with FDA authorization for the management of RET fusion-positive non-small-cell lung cancers
Faraat Ali, Kumari Neha, Garima Chauhan
Archives of Pharmacal Research.2022; 45(5): 309. CrossRef
Psychosocial Characteristics and Experiences in Patients with Multiple Endocrine Neoplasia Type 2 (MEN2) and Medullary Thyroid Carcinoma (MTC)
Robin Lockridge, Sima Bedoya, Taryn Allen, Brigitte C. Widemann, Srivandana Akshintala, John Glod, Lori Wiener
Children.2022; 9(6): 774. CrossRef
Aggressive clinical course of medullary thyroid microcarcinoma
Tamara Janić, Mirjana Stojković, Sanja Klet, Bojan Marković, Beleslin Nedeljković, Jasmina Ćirić, Miloš Žarković
Medicinski glasnik Specijalne bolnice za bolesti štitaste žlezde i bolesti metabolizma.2022; 27(85): 63. CrossRef
Comparative evaluation of somatostatin and CXCR4 receptor expression in different types of thyroid carcinoma using well-characterised monoclonal antibodies
Max Czajkowski, Daniel Kaemmerer, Jörg Sänger, Guido Sauter, Ralph M. Wirtz, Stefan Schulz, Amelie Lupp
BMC Cancer.2022;[Epub] CrossRef
Metastatic Risk Stratification of 2526 Medullary Thyroid Carcinoma Patients: A Study Based on Surveillance, Epidemiology, and End Results Database
Minh-Khang Le, Masataka Kawai, Toru Odate, Huy Gia Vuong, Naoki Oishi, Tetsuo Kondo
Endocrine Pathology.2022; 33(3): 348. CrossRef
Update on the Diagnosis and Management of Medullary Thyroid Cancer: What Has Changed in Recent Years?
Krzysztof Kaliszewski, Maksymilian Ludwig, Bartłomiej Ludwig, Agnieszka Mikuła, Maria Greniuk, Jerzy Rudnicki
Cancers.2022; 14(15): 3643. CrossRef
Immunotherapy of Neuroendocrine Neoplasms: Any Role for the Chimeric Antigen Receptor T Cells?
Giuseppe Fanciulli, Roberta Modica, Anna La Salvia, Federica Campolo, Tullio Florio, Nevena Mikovic, Alice Plebani, Valentina Di Vito, Annamaria Colao, Antongiulio Faggiano
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Preclinical Evaluation of Novel Tyrosine-Kinase Inhibitors in Medullary Thyroid Cancer
Davide Saronni, Germano Gaudenzi, Alessandra Dicitore, Silvia Carra, Maria Celeste Cantone, Maria Orietta Borghi, Andrea Barbieri, Luca Mignani, Leo J. Hofland, Luca Persani, Giovanni Vitale
Cancers.2022; 14(18): 4442. CrossRef
Rapid and long-lasting response to selpercatinib of paraneoplastic Cushing’s syndrome in medullary thyroid carcinoma
Marine Sitbon, Porhuoy Chou, Seydou Bengaly, Brigitte Poirot, Marie Laloi-Michelin, Laure Deville, Atanas Pachev, Ahouefa Kowo-Bille, Clement Dumont, Cécile N Chougnet
European Thyroid Journal.2022;[Epub] CrossRef
Ginsenoside Rg3 Alleviates Antithyroid Cancer Drug Vandetanib-Induced QT Interval Prolongation
Juan Zhang, Dan Luo, Fang Li, Zhiyi Li, Xiaoli Gao, Jie Qiao, Lin Wu, Miaoling Li, Shao Liang
Oxidative Medicine and Cellular Longevity.2021; 2021: 1. CrossRef
THE ROLE OF CALCITONIN IN THE PREOPERATIVE STAGE AS THE PREDICTOR OF MEDULLARY THYROID CANCER METASTASES
Volodymyr Palamarchuk , Viktor Smolyar , Oleksandr Tovkay, Oleksandr Nechay, Volodymyr Kuts , Revaz Sichinava , Oleh Mazur
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Bone Metabolism
Normocalcemic Primary Hyperparathyroidism: Need for a Standardized Clinical Approach: Guido Zavatta, Bart L. Clarke; Endocrinol Metab. 2021;36(3):525-535. Published online June 1, 2021; DOI: https://doi.org/10.3803/EnM.2021.1061

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Since normocalcemic primary hyperparathyroidism (NHPT) was first defined at the Third International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism in 2008, many papers have been published describing its prevalence and possible complications. Guidelines for the management of this condition are still lacking, and making the diagnosis requires fulfillment of strict criteria. Recent studies have shown that intermittent oscillations of serum calcium just below and slightly above the normal limits are very frequent, therefore challenging the assumption that serum calcium must be consistently normal to make the diagnosis. There is debate if these variations in serum calcium outside the normal range should be included under the rubric of NHPT or, rather, a milder form of classical primary hyperparathyroidism. Innovative approaches to define NHPT have been proposed that still need to be validated in prospective studies. Non-classical complications, especially cardiovascular complications, have been associated with NHPT, indicating that hyperparathyroidism may be a cardiovascular risk factor. New associations between parathyroid hormone (PTH) and several other comorbidities have also been reported from observational studies, suggesting that excessive PTH secretion might cause tissue dysfunction independent of serum calcium. Heterogeneous studies using different definitions of NHPT, however, make it difficult to draw definitive conclusions regarding the role of PTH excess when complications other than osteoporosis or kidney stones are described. This review will focus on clinical aspects and suggest an approach to NHPT.

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DXA-based bone strain index in normocalcemic primary hyperparathyroidism
Gaia Tabacco, Anda Mihaela Naciu, Carmelo Messina, Gianfranco Sanson, Luca Rinaudo, Roberto Cesareo, Stefania Falcone, Nicola Napoli, Fabio Massimo Ulivieri, Andrea Palermo
Osteoporosis International.2023; 34(5): 999. CrossRef
Iperparatiroidismo primario normocalcemico
Silvia Egiddi, Luigi Bonifazi Meffe, Anda Mihaela Naciu, Gaia Tabacco, Nicola Napoli, Andrea Palermo
L'Endocrinologo.2023; 24(3): 249. CrossRef
Evaluating Patients for Secondary Causes of Osteoporosis
E. Michael Lewiecki
Current Osteoporosis Reports.2022; 20(1): 1. CrossRef
Preoperative Thoracic Muscle Mass Predicts Bone Density Change After Parathyroidectomy in Primary Hyperparathyroidism
Seung Won Burm, Namki Hong, Seunghyun Lee, Gi Jeong Kim, Sang Hyun Hwang, Jongju Jeong, Yumie Rhee
The Journal of Clinical Endocrinology & Metabolism.2022; 107(6): e2474. CrossRef
Applications of Metabolomics in Calcium Metabolism Disorders in Humans
Beata Podgórska, Marta Wielogórska-Partyka, Joanna Godzień, Julia Siemińska, Michał Ciborowski, Małgorzata Szelachowska, Adam Krętowski, Katarzyna Siewko
International Journal of Molecular Sciences.2022; 23(18): 10407. CrossRef
Serum Calcium/Phosphorus Ratio in Biochemical Screening of Primary Hyperparathyroidism
Nagihan Bestepe, Fatma Neslihan Cuhaci, Burcak Polat, Berna Evranos Ogmen, Didem Ozdemir, Reyhan Ersoy, Bekir Cakir
Revista da Associação Médica Brasileira.2022; 68(12): 1668. CrossRef

Bone Metabolism
Update on Glucocorticoid Induced Osteoporosis: Soo-Kyung Cho, Yoon-Kyoung Sung; Endocrinol Metab. 2021;36(3):536-543. Published online June 1, 2021; DOI: https://doi.org/10.3803/EnM.2021.1021

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Glucocorticoids are used to treat many autoimmune and inflammatory diseases. However, an adverse systemic effect is a deleterious effect on bone, which may lead to glucocorticoid-induced osteoporosis, characterized by a rapid and transient increase in bone resorption and fracture risk, which may increase rapidly within 3 months of commencing oral glucocorticoids. Therefore, early risk assessment and intervention are crucial for preventing fractures in patients receiving glucocorticoids. Recent practice guidelines recommend an assessment for fracture risk in patients beginning or receiving glucocorticoids for more than 3 months, and they have suggested fracture risk assessment tool values for identifying patients who need preventive treatment. Bisphosphonates are currently the recommended first-line therapy for the prevention and treatment of glucocorticoid-induced osteoporosis. These have been shown to increase the bone mineral density in the spine and hip and to decrease the incidence of vertebral fractures. Recently, a more potent antiresorptive agent, denosumab, has been shown to increase the bone density in patients receiving glucocorticoids. Teriparatide has been shown to have a preventive effect on vertebral fractures, but not on nonvertebral fractures. In this article we aimed to provide an update on glucocorticoid-induced osteoporosis by focusing on the assessment of its risk and treatment options.

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Protective role of 3-oxypyridine derivatives in rats’ steroid-induced osteoporosis associated with reduced oxidative stress and recovery of nitric oxide formation
A. P. Danilenko, K. S. Trunov, M. V. Pokrovsky, L. M. Danilenko, M. V. Korokin, O. S. Gudyrev, A. A. Khentov, N. P. Masalytina, I. A. Tatarenkova, A. V. Cherednichenko, E. V. Boeva, I. S. Koklin, E. I. Taran
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Vitamin D Supplementation in Patients with Juvenile Idiopathic Arthritis
Chao-Yi Wu, Huang-Yu Yang, Shue-Fen Luo, Jing-Long Huang, Jenn-Haung Lai
Nutrients.2022; 14(8): 1538. CrossRef
A Review on the Molecular Mechanisms of Action of Natural Products in Preventing Bone Diseases
Innocent U. Okagu, Timothy P. C. Ezeorba, Rita N. Aguchem, Ikenna C. Ohanenye, Emmanuel C. Aham, Sunday N. Okafor, Carlotta Bollati, Carmen Lammi
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Jiang Huo, Yu Ding, Xinyuan Wei, Qi Chen, Bin Zhao
Journal of Biochemical and Molecular Toxicology.2022;[Epub] CrossRef
Comparison of denosumab and oral bisphosphonates for the treatment of glucocorticoid-induced osteoporosis: a systematic review and meta-analysis
Lianghai Jiang, Jian Dong, Jianwei Wei, Lantao Liu
BMC Musculoskeletal Disorders.2022;[Epub] CrossRef
Improvement in Glucocorticoid-Induced Osteoporosis on Switching from Bisphosphonates to Once-Weekly Teriparatide: A Randomized Open-Label Trial
Toshihiro Nanki, Mai Kawazoe, Kiyoko Uno, Wataru Hirose, Hiroaki Dobashi, Hiroshi Kataoka, Toshihide Mimura, Hiroshi Hagino, Hajime Kono
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Chang-Nam Son
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Bone Metabolism
Long-Term Treatment of Postmenopausal Osteoporosis: Jacques P. Brown; Endocrinol Metab. 2021;36(3):544-552. Published online June 22, 2021; DOI: https://doi.org/10.3803/EnM.2021.301

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Osteoporosis is an incurable chronic condition, like heart disease, diabetes, or hypertension. A large gap currently exists in the primary prevention of fractures, and studies show that an estimated 80% to 90% of adults do not receive appropriate osteoporosis management even in the secondary prevention setting. Case finding strategies have been developed and effective pharmacological interventions are available. This publication addresses how best to use the pharmacological options available for postmenopausal osteoporosis to provide lifelong fracture protection in patients at high and very high risk of fracture. The benefit of osteoporosis therapies far outweighs the rare risks.

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CircRNA hsa_circ_0006859 inhibits the osteogenic differentiation of BMSCs and aggravates osteoporosis by targeting miR-642b-5p/miR-483-3p and upregulating EFNA2/DOCK3
Peng Yin, Yuan Xue
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Resveratrol induces proliferation and differentiation of mouse pre-osteoblast MC3T3-E1 by promoting autophagy
Weiye Cai, Bin Sun, Chao Song, Fei Liu, Zhengliang Wu, Zongchao Liu
BMC Complementary Medicine and Therapies.2023;[Epub] CrossRef
Oridonin Attenuates Thioacetamide-Induced Osteoclastogenesis Through MAPK/NF-κB Pathway and Thioacetamide-Inhibited Osteoblastogenesis Through BMP-2/RUNX2 Pathway
XiaoLi Jin, Jia Xu, Fanfan Yang, Jin Chen, Feng Luo, Bin Xu, Jian Xu
Calcified Tissue International.2023; 112(6): 704. CrossRef
Phytochemical Compounds Involved in the Bone Regeneration Process and Their Innovative Administration: A Systematic Review
Alina Hanga-Farcaș, Florina Miere (Groza), Gabriela Adriana Filip, Simona Clichici, Luminita Fritea, Laura Grațiela Vicaș, Eleonora Marian, Annamaria Pallag, Tunde Jurca, Sanda Monica Filip, Mariana Eugenia Muresan
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Benefits of lumican on human bone health: clinical evidence using bone marrow aspirates
Yun Sun Lee, So Jeong Park, Jin Young Lee, Eunah Choi, Beom-Jun Kim
The Korean Journal of Internal Medicine.2022; 37(4): 821. CrossRef
ED-71 inhibited osteoclastogenesis by enhancing EphrinB2–EphB4 signaling between osteoclasts and osteoblasts in osteoporosis
Yuan Zhang, Yuying Kou, Panpan Yang, Xing Rong, Rong Tang, Hongrui Liu, Minqi Li
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Effects of Muscles on Bone Metabolism—with a Focus on Myokines
Beom-Jun Kim
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Evaluation of the tolerability of zoledronic acid preparations for parenteral administration
I. A. Shafieva, S. V. Bulgakova, A. V. Shafieva
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Baohui Wang, Yindi Sun, Da Shi, Xiuwei Han, Na Liu, Bo Wang, Zhijun Liao
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Jacques P. Brown, Andrew Don-Wauchope, Pierre Douville, Caroline Albert, Samuel D. Vasikaran
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An Acid-Sensitive Bone Targeting Delivery System Carrying Acacetin Prevents Osteoporosis in Ovariectomized Mice
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Endocrinology and Metabolism.2021; 36(6): 1211. CrossRef

Adrenal Gland
Asian Conference on Tumor Ablation Guidelines for Adrenal Tumor Ablation: Byung Kwan Park, Masashi Fujimori, Shu-Huei Shen, Uei Pua; Endocrinol Metab. 2021;36(3):553-563. Published online June 1, 2021; DOI: https://doi.org/10.3803/EnM.2021.1008

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Abstract PDF PubReader ePub Crossref - TDM: Thermal ablation is a good alternative treatment in patients who are unable to undergo adrenalectomy. Even though the Asian Conference on Tumor Ablation (ACTA) has been held for many years, adrenal ablation guidelines have not been established. No guidelines for adrenal ablation are established in American and European countries, either. The aim of this review was to introduce the first version of ACTA guidelines for adrenal tumor ablation.

Miscellanenous
Cushing Syndrome Associated Myopathy: It Is Time for a Change: Martin Reincke; Endocrinol Metab. 2021;36(3):564-571. Published online June 18, 2021; DOI: https://doi.org/10.3803/EnM.2021.1069

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Cushing syndrome is the result of excessive levels of glucocorticoids. Endogenous Cushing syndrome is rare with an incidence of two to three cases per million per year. Clinically, the presentation consists of a characteristic phenotype including skin symptoms and metabolic manifestations. A frequent co-morbidity with high impact on quality of life is Cushing syndrome associated myopathy. It characteristically affects the proximal myopathy, impairing stair climbing and straightening up. The pathophysiology is complex and involves protein degradation via the forkhead box O3 (FOXO3) pathway, intramuscular fat accumulation, and inactivity-associated muscle atrophy. Surgical remission of Cushing syndrome is the most important step for recovery of muscle function. Restoration depends on age, co-morbidities and postoperative insulin-like growth factor concentrations. At average, functionality remains impaired during the long-term compared to age and sex matched control persons. Growth hormone therapy in individuals with impaired growth hormone secretion could be an option but has not been proved in a randomized trial.

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The Link between Mitochondrial Dysfunction and Sarcopenia: An Update Focusing on the Role of Pyruvate Dehydrogenase Kinase 4
Min-Ji Kim, Ibotombi Singh Sinam, Zerwa Siddique, Jae-Han Jeon, In-Kyu Lee
Diabetes & Metabolism Journal.2023; 47(2): 153. CrossRef
Intelligent Systems for Muscle Tracking: A Review on Sensor‐Algorithm Synergy
Arjun Putcha, Tien Nguyen, Regina Smith, Rachel Choffin, Wubin Bai
Advanced Intelligent Systems.2023; : 2200351. CrossRef
Sarcopenia in youth
Han Na Jung, Chang Hee Jung, You-Cheol Hwang
Metabolism.2023; 144: 155557. CrossRef
Morbidität und Mortalität beim Cushing-Syndrom
Frederick Vogel, Leah Braun, Martin Reincke
Der Internist.2022; 63(1): 34. CrossRef
Pathophysiology of Mild Hypercortisolism: From the Bench to the Bedside
Vittoria Favero, Arianna Cremaschi, Chiara Parazzoli, Alberto Falchetti, Agostino Gaudio, Luigi Gennari, Alfredo Scillitani, Fabio Vescini, Valentina Morelli, Carmen Aresta, Iacopo Chiodini
International Journal of Molecular Sciences.2022; 23(2): 673. CrossRef
Long‐term morbidity and mortality in patients with Cushing's syndrome
Leah T. Braun, Frederick Vogel, Martin Reincke
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Clinical presentation and etiology of Cushing's syndrome: Data from ERCUSYN
Elena Valassi
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Pyruvate dehydrogenase kinase 4 promotes ubiquitin–proteasome system‐dependent muscle atrophy
Ibotombi Singh Sinam, Dipanjan Chanda, Themis Thoudam, Min‐Ji Kim, Byung‐Gyu Kim, Hyeon‐Ji Kang, Jung Yi Lee, Seung‐Hoon Baek, Shin‐Yoon Kim, Bum Jin Shim, Dongryeol Ryu, Jae‐Han Jeon, In‐Kyu Lee
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Consensus on diagnosis and management of Cushing's disease: a guideline update
Maria Fleseriu, Richard Auchus, Irina Bancos, Anat Ben-Shlomo, Jerome Bertherat, Nienke R Biermasz, Cesar L Boguszewski, Marcello D Bronstein, Michael Buchfelder, John D Carmichael, Felipe F Casanueva, Frederic Castinetti, Philippe Chanson, James Findling
The Lancet Diabetes & Endocrinology.2021; 9(12): 847. CrossRef

Editorial

Diabetes, Obesity and Metabolism
Identification of Protein Z as a Potential Novel Biomarker for the Diagnosis of Prediabetes: Seung-Hoi Koo; Endocrinol Metab. 2021;36(3):572-573. Published online June 28, 2021; DOI: https://doi.org/10.3803/EnM.2021.303

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Original Articles

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

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

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ASO Author Reflections: Active Surveillance may be Possible in Patients with T1b Papillary Thyroid Carcinoma Over 55 Years of Age Without High-Risk Features on Preoperative Examinations
Ho-Ryun Won, Eonju Jeon, Da Beom Heo, Jae Won Chang, Minho Shong, Je Ryong Kim, Hyemi Ko, Yea Eun Kang, Hyon-Seung Yi, Ju Hee Lee, Kyong Hye Joung, Ji Min Kim, Younju Lee, Sung-Woo Kim, Young Ju Jeong, Yong Bae Ji, Kyung Tae, Bon Seok Koo
Annals of Surgical Oncology.2023; 30(4): 2254. CrossRef
Outcomes and Trends of Treatments in High‐Risk Differentiated Thyroid Cancer
Arash Abiri, Khodayar Goshtasbi, Sina J. Torabi, Edward C. Kuan, William B. Armstrong, Tjoson Tjoa, Yarah M. Haidar
Otolaryngology–Head and Neck Surgery.2023; 168(4): 745. CrossRef
Current Controversies in Low-Risk Differentiated Thyroid Cancer: Reducing Overtreatment in an Era of Overdiagnosis
Timothy M Ullmann, Maria Papaleontiou, Julie Ann Sosa
The Journal of Clinical Endocrinology & Metabolism.2023; 108(2): 271. CrossRef
Age-Dependent Clinicopathological Characteristics of Patients with T1b Papillary Thyroid Carcinoma: Implications for the Possibility of Active Surveillance
Ho-Ryun Won, Eonju Jeon, Da Beom Heo, Jae Won Chang, Minho Shong, Je Ryong Kim, Hyemi Ko, Yea Eun Kang, Hyon-Seung Yi, Ju Hee Lee, Kyong Hye Joung, Ji Min Kim, Younju Lee, Sung-Woo Kim, Young Ju Jeong, Yong Bae Ji, Kyung Tae, Bon Seok Koo
Annals of Surgical Oncology.2023; 30(4): 2246. CrossRef
Thyroid stimulating hormone suppression and recurrence after thyroid lobectomy for papillary thyroid carcinoma
Mi Rye Bae, Sung Hoon Nam, Jong-Lyel Roh, Seung-Ho Choi, Soon Yuhl Nam, Sang Yoon Kim
Endocrine.2022; 75(2): 487. CrossRef
The Concept of Economic Evaluation and Its Application in Thyroid Cancer Research
Kyungsik Kim, Mijin Kim, Woojin Lim, Bo Hyun Kim, Sue K. Park
Endocrinology and Metabolism.2021; 36(4): 725. CrossRef

Thyroid
Insights from a Prospective Follow-up of Thyroid Function and Autoimmunity among COVID-19 Survivors: David Tak Wai Lui, Chi Ho Lee, Wing Sun Chow, Alan Chun Hong Lee, Anthony Raymond Tam, Carol Ho Yi Fong, Chun Yiu Law, Eunice Ka Hong Leung, Kelvin Kai Wang To, Kathryn Choon Beng Tan, Yu Cho Woo, Ching Wan Lam, Ivan Fan Ngai Hung, Karen Siu Ling Lam; Endocrinol Metab. 2021;36(3):582-589. Published online June 8, 2021; DOI: https://doi.org/10.3803/EnM.2021.983

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Abstract PDF PubReader ePub Crossref - TDM

Background
The occurrence of Graves’ disease and Hashimoto thyroiditis after coronavirus disease 2019 (COVID-19) raised concerns that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may trigger thyroid autoimmunity. We aimed to address the current uncertainties regarding incident thyroid dysfunction and autoimmunity among COVID-19 survivors.
Methods
We included consecutive adult COVID-19 patients without known thyroid disorders, who were admitted to Queen Mary Hospital from July 21 to September 21, 2020 and had serum levels of thyroid-stimulating hormone, free thyroxine, free triiodothyronine (fT3), and anti-thyroid antibodies measured both on admission and at 3 months.
Results
In total, 122 patients were included. Among 20 patients with abnormal thyroid function tests (TFTs) on admission (mostly low fT3), 15 recovered. Among 102 patients with initial normal TFTs, two had new-onset abnormalities that could represent different phases of thyroiditis. Among 104 patients whose anti-thyroid antibody titers were reassessed, we observed increases in anti-thyroid peroxidase (TPO) (P<0.001) and anti-thyroglobulin (P<0.001), but not anti-thyroid stimulating hormone receptor titers (P=0.486). Of 82 patients with negative anti-TPO findings at baseline, 16 had a significant interval increase in anti-TPO titer by >12 U, and four became anti-TPO-positive. Worse baseline clinical severity (P=0.018), elevated C-reactive protein during hospitalization (P=0.033), and higher baseline anti-TPO titer (P=0.005) were associated with a significant increase in anti-TPO titer.
Conclusion
Most patients with thyroid dysfunction on admission recovered during convalescence. Abnormal TFTs suggestive of thyroiditis occurred during convalescence, but infrequently. Importantly, our novel observation of an increase in anti-thyroid antibody titers post-COVID-19 warrants further follow-up for incident thyroid dysfunction among COVID-19 survivors.

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Réka Garai, Péter Krivácsy, Vivien Herczeg, Fanni Kovács, Bálint Tél, Judit Kelemen, Anna Máthé, Eszter Zsáry, Johanna Takács, Dániel Sándor Veres, Attila J. Szabó
Pediatric Research.2023; 93(6): 1616. CrossRef
T Cell Receptor Sequences Amplified during Severe COVID-19 and Multisystem Inflammatory Syndrome in Children Mimic SARS-CoV-2, Its Bacterial Co-Infections and Host Autoantigens
Robert Root-Bernstein, Elizabeth Churchill, Shelby Oliverio
International Journal of Molecular Sciences.2023; 24(2): 1335. CrossRef
A Literature Review on SARS-CoV-2 and Other Viruses in Thyroid Disorders: Environmental Triggers or No-Guilty Bystanders?
Francesca Gorini, Cristina Vassalle
International Journal of Environmental Research and Public Health.2023; 20(3): 2389. CrossRef
Thyroid dysfunction as a long-term post-COVID-19 complication in mild-to-moderate COVID-19
Vesselina Yanachkova, Teodora Stankova, Radiana Staynova
Biotechnology & Biotechnological Equipment.2023; 37(1): 194. CrossRef
The Influence of SARS-CoV-2 Infection on the Thyroid Gland
Aleksandra Piekarska, Marta Góral, Marta Kozula, Aleksandra Jawiarczyk-Przybyłowska, Katarzyna Zawadzka, Marek Bolanowski
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Deepika Patel, Dukhabandhu Naik, Sadishkumar Kamalanathan, Kadhiravan Tamilarasu, Jayaprakash Sahoo, Ayan Roy, Chandhana Merugu, Varun Suryadevara
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The Spectrum of Thyroid Function Tests and Autoantibodies During Hospitalization and After Six Months of Discharge in COVID-19 Patients: Does COVID-19 Trigger Autoimmunity?
Ziynet Alphan Uc, Pinar Yagcı, Zelal Adibelli, Cevdet Duran
Endocrine Research.2023; : 1. CrossRef
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Alessandro Rossini, Sara Cassibba, Francesca Perticone, Simone Vasilij Benatti, Serena Venturelli, Greta Carioli, Arianna Ghirardi, Marco Rizzi, Tiziano Barbui, Roberto Trevisan, Silvia Ippolito
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A prospective follow-up of thyroid volume and thyroiditis features on ultrasonography among survivors of predominantly mild to moderate COVID-19
Man Him Matrix Fung, David Tak Wai Lui, Keith Wan Hang Chiu, Sherman Haynam Lee, Chi Ho Lee, Wing Sun Chow, Alan Chun Hong Lee, Anthony Raymond Tam, Polly Pang, Tip Yin Ho, Carol Ho Yi Fong, Connie Hong Nin Loong, Chun Yiu Law, Kelvin Kai Wang To, Ching W
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Study on Clinicopathological Features and Risk Factors of Patients with Multiple Primary Breast Cancers and Thyroid Disease
Jie Li, Yonghong Liu, Jian Jin, Qingfeng Shi, Yanting Ji, Bo Zhang, Pengfei Hu, Jinghua Pan
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Autoimmune complications of COVID‐19
Niloufar Yazdanpanah, Nima Rezaei
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The Independent Association of TSH and Free Triiodothyronine Levels With Lymphocyte Counts Among COVID-19 Patients
David Tak Wai Lui, Chi Ho Lee, Wing Sun Chow, Alan Chun Hong Lee, Anthony Raymond Tam, Polly Pang, Tip Yin Ho, Chloe Yu Yan Cheung, Carol Ho Yi Fong, Chun Yiu Law, Kelvin Kai Wang To, Ching Wan Lam, Kathryn Choon Beng Tan, Yu Cho Woo, Ivan Fan Ngai Hung,
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D. T. W. Lui, C. H. Lee, W. S. Chow, A. C. H. Lee, A. R. Tam, C. Y. Y. Cheung, C. H. Y. Fong, S. T. M. Kwok, C. Y. Law, K. K. W. To, C. W. Lam, K. C. B. Tan, Y. C. Woo, I. F. N. Hung, K. S. L. Lam
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Abdallah Al-Salameh, Noémie Scherman, Imane Adda, Juliette André, Yoann Zerbib, Julien Maizel, Jean-Daniel Lalau, Etienne Brochot, Claire Andrejak, Rachel Desailloud
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Long COVID in Patients With Mild to Moderate Disease: Do Thyroid Function and Autoimmunity Play a Role?
David Tak Wai Lui, Chi Ho Lee, Wing Sun Chow, Alan Chun Hong Lee, Anthony Raymond Tam, Polly Pang, Tip Yin Ho, Carol Ho Yi Fong, Chun Yiu Law, Eunice Ka Hong Leung, Kelvin Kai Wang To, Kathryn Choon Beng Tan, Yu Cho Woo, Ching Wan Lam, Ivan Fan Ngai Hung,
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Rafael Silvestre Knack, Taliê Hanada, Renata Silvestre Knack, Kamilla Mayr
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Higher SARS-CoV-2 viral loads correlated with smaller thyroid volumes on ultrasound among male COVID-19 survivors
David Tak Wai Lui, Matrix Man Him Fung, Keith Wan Hang Chiu, Chi Ho Lee, Wing Sun Chow, Alan Chun Hong Lee, Anthony Raymond Tam, Polly Pang, Tip Yin Ho, Carol Ho Yi Fong, Connie Hong Nin Loong, Wade Wei Wong, Cassandra Yuen Yan Lee, Chun Yiu Law, Kelvin K
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Thyroid
Effect of Cigarette Smoking on Thyroid Cancer: Meta-Analysis: Joon-Hyop Lee, Young Jun Chai, Ka Hee Yi; Endocrinol Metab. 2021;36(3):590-598. Published online May 26, 2021; DOI: https://doi.org/10.3803/EnM.2021.954

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Abstract PDF Supplementary Material PubReader ePub Crossref - TDM

Background
Although smoking is generally carcinogenic, its effect on thyroid cancers is still subject to controversy. The purpose of this study was to summarize the role of smoking in relation to thyroid cancer occurrence.
Methods
We performed a meta-analysis of 24 eligible studies: 21 case-control studies and three prospective cohort studies. The summary odds ratio (OR) and 95% confidence interval (CI) of all studies were acquired based on random effect model. Further subgroup analyses were conducted according to gender, histological type of thyroid cancer, and smoking status of patients for the case-control studies.
Results
The summary effect size indicated a negative association of smoking for thyroid cancer (OR, 0.798; 95% CI, 0.681 to 0.935). From the subgroup analyses for the case-control studies, reduced risk of thyroid cancer was observed in both men (OR, 0.734; 95% CI, 0.553 to 0.974) and women (OR, 0.792; 95% CI, 0.700 to 0.897). The protective effect of smoking was observed in studies in which thyroid cancer was limited to differentiated thyroid cancers (DTCs) (OR, 0.798; 95% CI, 0.706 to 0.902).
Conclusion
Our results suggests that smoking may have a protective effect on thyroid cancer, especially on DTCs. Further studies with larger sample sizes should be conducted in elucidating the dose and time dependent effect of smoking on thyroid cancer with specific focus on the types of thyroid cancers.

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Relationship between Serum Levels of Selenium and Thyroid Cancer: A Systematic Review and Meta-Analysis
Runhua Hao, Ping Yu, Lanlan Gui, Niannian Wang, Da Pan, Shaokang Wang
Nutrition and Cancer.2023; 75(1): 14. CrossRef
Longitudinal Changes in Smoking Habits in Women and Subsequent Risk of Cancer
Thi Xuan Mai Tran, Soyeoun Kim, Huiyeon Song, Boyoung Park
American Journal of Preventive Medicine.2022; 63(6): 894. CrossRef

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

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