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Volume 36(3); June 2021
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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
  • 14,503 View
  • 397 Download
  • 4 Web of Science
  • 4 Crossref
AbstractAbstract PDFPubReader   ePub   
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.

Citations

Citations to this article as recorded by  
  • Multidimensional exploration of the bitterness amelioration effect of roasting on Wuyi Rock tea
    Weiying Su, Li Ni, Yizhe Chen, Daoliang Wang, Chih-Cheng Lin, Yuan Liu, Zhibin Liu
    Food Chemistry.2024; 437: 137954.     CrossRef
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    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
Close layer
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
  • 9,478 View
  • 352 Download
  • 9 Web of Science
  • 8 Crossref
AbstractAbstract PDFPubReader   ePub   
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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    Saniya Khan, Sunil Kumar, Sourya Acharya, Anil Wanjari
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  • Novel Potential Targets for Function-Promoting Therapies: Orphan Nuclear Receptors, Anti-inflammatory Drugs, Troponin Activators, Mas Receptor Agonists, and Urolithin A
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  • 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
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    Marcela Kanova, Pavel Kohout
    International Journal of Molecular Sciences.2022; 23(15): 8396.     CrossRef
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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
  • 5,527 View
  • 351 Download
  • 7 Web of Science
  • 11 Crossref
AbstractAbstract PDFPubReader   ePub   
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.

Citations

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    Eye.2023; 37(16): 3382.     CrossRef
  • Methimazole, an Effective Neutralizing Agent of the Sulfur Mustard Derivative 2-Chloroethyl Ethyl Sulfide
    Albert Armoo, Tanner Diemer, Abigail Donkor, Jerrod Fedorchik, Severine Van slambrouck, Rachel Willand-Charnley, Brian A. Logue
    ACS Bio & Med Chem Au.2023; 3(5): 448.     CrossRef
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    Endocrinology and Metabolism.2021; 36(6): 1277.     CrossRef
Close layer
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
  • 10,432 View
  • 592 Download
  • 19 Web of Science
  • 22 Crossref
AbstractAbstract PDFPubReader   ePub   
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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Close layer
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
  • 19,992 View
  • 1,916 Download
  • 33 Web of Science
  • 37 Crossref
AbstractAbstract PDFPubReader   ePub   
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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Close layer
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
  • 7,187 View
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  • 13 Web of Science
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AbstractAbstract PDFPubReader   ePub   
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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Close layer
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
  • 5,620 View
  • 375 Download
  • 8 Web of Science
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AbstractAbstract PDFPubReader   ePub   
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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Close layer
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
  • 17,269 View
  • 1,003 Download
  • 45 Web of Science
  • 48 Crossref
AbstractAbstract PDFPubReader   ePub   
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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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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AbstractAbstract PDFPubReader   ePub   
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.

Citations

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

Citations

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    Ja Kyung Lee, Eu Jeong Ku, Su-jin Kim, Woochul Kim, Jae Won Cho, Kyong Yeun Jung, Hyeong Won Yu, Yea Eun Kang, Mijin Kim, Hee Kyung Kim, Junsun Ryu, June Young Choi
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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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AbstractAbstract PDFPubReader   ePub   
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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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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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
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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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
  • 4,257 View
  • 122 Download
  • 2 Web of Science
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
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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    Yang-Yang Tang, Wang-Dong Xu, Lu Fu, Xiao-Yan Liu, An-Fang Huang
    Clinical Rheumatology.2024; 43(1): 489.     CrossRef
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    Lu‐Qi Yang, Zhen Qin, Lu Fu, Wang‐Dong Xu
    International Journal of Rheumatic Diseases.2024;[Epub]     CrossRef
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