Causal linkage of Graves' disease with aging: Mendelian randomization analysis of telomere length and age-related phenotypes.

BACKGROUND: Aging is an irreversible progressive decline in physical function. Graves' disease (GD) is a common cause of hyperthyroidism and is characterized by elevated levels of the thyroid hormone (TH). High TH levels are associated with aging and a shortened lifespan. The causal relationship between GD and aging has yet to be investigated. METHODS: We used genome-wide association study (GWAS) datasets and Mendelian randomization (MR) analysis to explore the causal link between GD and aging. To assess the statistical power of instrumental variables (IVs), F-statistics and R2 were used. MR analysis was conducted using inverse-variance weighting (IVW), MR-Egger, weighted median, and weighted mode. The odds ratio (OR) and 95% CI were calculated to estimate the relative risk of GD to the outcomes. The Cochran Q test, I2, MR-PRESSO test, and MR-Egger regression intercept were calculated using statistical and leave-one-out analyses to test the heterogeneity, horizontal pleiotropy, and stability of the IVs on the outcomes. RESULTS: F-statistics of the five IVs were greater than 10, and the R2 values ranged from 0.033 to 0.156 (R2 > 0.01). According to the results of the IVW analysis, GD had no causal effect on facial aging (p = 0.189), age-related macular degeneration (p = 0.346), and Alzheimer's disease (p = 0.479). There was a causal effect of GD on the remaining outcomes: telomere length (TL) (OR = 0.982; 95%CI:0.969-0.994; p = 0.004), senile cataract (OR = 1.031; 95%CI:1.002-1.060; p = 0.033), age-related hearing impairment (OR = 1.009; 95%CI:1.004-1.014; p = 0.001), chronic obstructive pulmonary disease (COPD) (OR = 1.055; 95%CI:1.008-1.103; p = 0.020), and sarcopenia (OR = 1.027; 95%CI:1.009-1.046; p = 0.004). CONCLUSIONS: GD accelerates the occurrence of age-related phenotypes including TL, senile cataracts, age-related hearing impairment, COPD, and sarcopenia. In contrast, there are no causal linkages between GD and facial aging, age-related macular degeneration, or Alzheimer's disease. Further experimental studies could be conducted to elucidate the mechanisms by which GD facilitates aging, which could help slow down the progress of aging.

Effect of methimazole treatment on Th1, Th17, and Th22 lymphocytes in pediatric Graves' disease patients.

Graves' disease is the leading cause of autoimmune hyperthyroidism. Thyroid hormones are an essential element of the endocrine system, playing a pivotal role in the body's development, especially important in children with intensified growth. Disturbance within thyroid tissue certainly affected the whole body. Nowadays, numerous research studies indicate different factors contributing to the onset of the disease; however, the exact pathomechanism of Graves' disease is still not fully understood, especially in the context of immune-related processes. Th1, Th17, and Th22 effector lymphocytes were found to be crucial participants in the disease outcome, as well as in autoimmune diseases. Here, our study aimed at assessing selected effector T lymphocytes, Th1, Th17, and Th22, in newly diagnosed pediatric Graves' disease patients, together with their association with thyroid-related parameters and the potential outcome of disease management. We indicated significant increases in the frequencies and absolute numbers of selected effector lymphocytes in Graves' disease patients. In addition, their mutual ratios, as well as Th1/Th17, Th/Th22, and Th17/Th22, seem to be significant in those diseases. Notably, low Th17/Th22 ratio values were distinguished as potential prognostic factors for normalizing TSH levels in response to methimazole treatment. To sum up, our research determines the crucial contribution of Th1, Th17, and Th22 cells in the pathogenesis of Graves' disease. Moreover, the mentioned subset of T cells is highly likely to play a substantial role in the potential prediction of therapy outcomes.

Chronic thyrotoxic myopathy development is associated with thyroid hormone sensitivity index, predicted by lower-limb fatigue and the squat-up test.

Thyroid hormones (THs) may affect chronic thyrotoxic myopathy (CTM). The relationship between TH sensitivity and CTM is inconsistent. We aimed to investigate the associations between TH sensitivity and the risk of CTM and to screen potential CTMs with strength and function tests. A total of 162 Chinese patients (36.58% men) with Graves' disease were enrolled and divided into CTM and non-CTM groups. TH and sensitivity indices were measured. Muscle power and function were assessed by grip, upper-limb fatigue (ULFT), lower-limb fatigue (LLFT), and squat-up (SUT) tests, and walking pace. Association between sensitivity to TH indices and the risk of developing CTM was assessed via multivariate logistic regression. The diagnostic effectiveness of muscle power and function for predicting CTM was evaluated via receiver operating characteristic (ROC) curves. Thyroid feedback quantile-based index FT3 (TFQIFT3) and the parametric TFQIFT3 (PTFQIFT3), TFQIFT4, and PTFQIFT4 were positively associated with CTM risk by using inverse probability of treatment weighting multivariate logistic regression. For each 1-SD increase in TFQIFT3 and PTFQIFT3, TFQIFT4 and PTFQIFT4, the odds ratios for CTM were 1.67 (95% CI = 1.17-2.48) ,1.64 (95% CI = 1.51-2.93), 1.60 (95%CI = 1.12-2.32), 1.58 (95%CI = 1.11-2.30), respectively. LLFT and SUT best predicted male/female CTM, respectively (AUC = 0.89/0.85). In Graves' disease patients, TH sensitivity is associated with CTM development, which can be predicted by SUT and LLFT results.

The association between methimazole tapering and intractable Graves' disease in children.

BACKGROUND: The aim of this study was to find predictive factors for intractable Graves' disease (GD). METHODS: Ninety-three GD patients who visited two pediatric endocrinology clinics from March 2009 to August 2019 were involved in this study. Data were collected on the methimazole (MZ) dosages prescribed from their first visits to their fifth visits. The amount of tapered dosage was presented as a "tapering velocity" (dosage difference (mg/m2)/follow-up interval (months)). The relationship between the tapering velocity and the remission rate of GD was analyzed. Remission of GD was defined as having a total period of MZ treatment less than 5 years with no relapse after MZ withdrawal for at least more than a year. RESULTS: Of 93 patients diagnosed with GD, 26 patients (28.0%) were classified as the "remission group" and 67 (72.0%) were classified as the "intractable group." The frequency of goiter was significantly higher in the intractable group (p = 0.031). Multivariate logistic analysis revealed that the tapering velocity change from the first to the fifth visit significantly influenced the risk of intractable GD: odds ratio (OR) = 0.598, 95% confidence interval (CI) 0.413-0.865, p = 0.006. An accompanying goiter at the time of diagnosis (OR = 4.706 95% CI 1.315-16.847, p = 0.017) and thyroid stimulation hormone receptor antibody titer (OR = 1.032 95% CI 1.002-1.062, p = 0.034) were also found to be independent factors associated with intractable progress in GD. CONCLUSION: Difficulty in tapering the MZ dosage in the first 4 months of treatment was an independent predicting factor for intractable GD.

Artificial intelligence-based CT-free quantitative thyroid SPECT for thyrotoxicosis: study protocol of a multicentre, prospective, non-inferiority study.

INTRODUCTION: Technetium thyroid uptake (TcTU) measured by single-photon emission CT/CT (SPECT/CT) is an important diagnostic tool for the differential diagnosis of Graves' disease and destructive thyroiditis. Artificial intelligence (AI) may reduce CT-induced radiation exposure by substituting the role of CT in attenuation correction (AC) and thyroid segmentation, thus realising CT-free SPECT. This study aims to compare the diagnostic accuracy for the differential diagnosis of thyrotoxicosis between CT-free SPECT and SPECT/CT. METHODS AND ANALYSIS: The AI-based CT-free SPECT is a single-blind, multicentre, prospective, non-inferiority, clinical trial with a paired design conducted in the Republic of Korea. Eligible participants are adult (≥19 years old) thyrotoxicosis patients without a previous history of hyperthyroidism or hypothyroidism. Approximately 160 subjects will be screened for quantitative thyroid SPECT/CT using Tc-99m pertechnetate. CT-free thyroid SPECT will be realised using only SPECT data by the trained convolutional neural networks. TcTU will be calculated by SPECT/CT and CT-free SPECT in each subject. The primary endpoint is the accuracy of diagnosing Graves' disease using TcTU. The trial will continue until 152 completed datasets have been enrolled to assess whether the 95% (two-sided) lower confidence limit of the accuracy difference (CT-free SPECT accuracy-SPECT/CT accuracy) for Graves' disease is greater than -0.1. The secondary endpoints include the accuracy of diagnosing destructive thyroiditis and predicting the need for antithyroid drug prescription within 1 month of the SPECT/CT. ETHICS AND DISSEMINATION: The study protocol has been approved by the institutional review board of Seoul National University Bundang Hospital (IRB No. B-2304-824-301), Konkuk University Medical Center (IRB No. 2023-05-022-006) and Chonnam National University Hospital (IRB No. CNUH-2023-108). Findings will be disseminated as reports, presentations and peer-reviewed journal articles. TRIAL REGISTRATION NUMBER: KCT0008387, Clinical Research Information Service of the Republic of Korea (CRIS).

Thyrotoxic Periodic Paralysis: A Rare Cause of Quadriparesis in a Young and Seemingly Healthy Patient.

Hypokalemia is a common laboratory finding in hospitalized patients, typically resulting from insufficient potassium intake, renal or gastrointestinal losses, or intracellular shifts. While the underlying cause is often easily identifiable, certain cases present diagnostic challenges, and if left unrecognized, the consequences can be life-threatening. We report a rare and atypical case of severe symptomatic hypokalemia as the initial presentation of newly diagnosed Graves' disease. The condition was caused by thyrotoxic periodic paralysis, a rare but serious complication of thyrotoxicosis, predominantly seen in East Asian populations. This disorder is characterized by episodes of acute, reversible muscle weakness associated with transient hypokalemia, which increases the risk of falls and traumatic injuries. The prompt identification of the etiology in such cases is critical for preventing recurrence and avoiding potentially fatal complications.

Comparison of Thyroid Size-Specific Radioiodine Dose and New Modified Dose Calculation in the Treatment of Graves' Disease.

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

Unveiling the Role of Gut Microbiota and Metabolites in Autoimmune Thyroid Diseases: Emerging Perspectives.

Autoimmune thyroid diseases (AITDs) are among the most prevalent organ-specific autoimmune disorders, with thyroid hormones playing a pivotal role in the gastrointestinal system's structure and function. Emerging evidence suggests a link between AITDs and the gut microbiome, which is a diverse community of organisms that are essential for digestion, absorption, intestinal homeostasis, and immune defense. Recent studies using 16S rRNA and metagenomic sequencing of fecal samples from AITD patients have revealed a significant correlation between a gut microbiota imbalance and the severity of AITDs. Progress in animal models of autoimmune diseases has shown that intervention in the gut microbiota can significantly alter the disease severity. The gut microbiota influences T cell subgroup differentiation and modulates the pathological immune response to AITDs through mechanisms involving short-chain fatty acids (SCFAs), lipopolysaccharides (LPSs), and mucosal immunity. Conversely, thyroid hormones also influence gut function and microbiota composition. Thus, there is a bidirectional relationship between the thyroid and the gut ecosystem. This review explores the pathogenic mechanisms of the gut microbiota and its metabolites in AITDs, characterizes the gut microbiota in Graves' disease (GD) and Hashimoto's thyroiditis (HT), and examines the interactions between the gut microbiota, thyroid hormones, T cell differentiation, and trace elements. The review aims to enhance understanding of the gut microbiota-thyroid axis and proposes novel approaches to mitigate AITD severity through gut microbiota modulation.

Cancer Risks of Patients with Graves' Disease Who Received Antithyroid Drugs as Initial Treatment: A Nationwide Population-Based Analysis.

Background: Population-based studies that examine the associations between hyperthyroidism and cancer risk have yielded inconsistent results. It remains unclear whether the risks of different cancers increase in patients with Graves' disease (GD) who received antithyroid drugs (ATDs) as initial treatment. We aimed to determine whether cancer risk increases in patients with GD, compared with controls. Methods: This nationwide retrospective cohort study utilized data from the National Health Information Database of South Korea. We included 29,502 patients aged >20 years with GD, who received ATDs as initial treatment, and 57,173 age- and sex-matched controls. The primary outcome was the incidence of various types of cancers. Hazard ratios (HRs) with confidence intervals (CIs) for cancer risk were estimated using Cox proportional hazards models. We also analyzed HR by follow-up period since the diagnosis of GD, accounting for surveillance effect. Results: The risk of biliary tract and pancreatic cancers (HR: 1.41, CI: 1.24-1.60), thyroid cancer (HR: 15.51, CI: 12.29-19.57), prostate cancer (HR: 1.48, CI: 1.28-1.71), and ovarian cancer (HR: 1.31, CI: 1.13-1.52) was elevated in the GD group than in the control group even after the first year of follow-up was excluded. The increased risk of these cancers persisted after a follow-up period of more than 5 years. The risk of thyroid cancer in patients with GD was higher during the initial follow-up period (1 to <2 years) (HR: 19.35, CI: 7.66-48.87) compared with that in the follow-up period exceeding 2 years. The cancer risk estimates remained significant after excluding patients with GD who underwent subsequent radioactive iodine therapy. Conclusion: In this large-scale population-based study, GD was associated with increased risks of biliary tract and pancreatic, prostate, ovarian, and thyroid cancers. The increased risk of thyroid cancer, particularly during the initial follow-up period, may be a surveillance effect.

[Acute myocarditis secondary to Graves' disease: A case report]. / Myocardite aiguë secondaire à une maladie de Basedow : à propos d'un cas.

The relationships between the thyroid and the heart are close and complex. In rare cases, hyperthyroidism induced by Graves' disease can be complicated by an acute myocarditis, which may be life-threatening. We report the case of a 41-year-old woman with Graves' disease not controlled by antithyroid drugs, hospitalized for odynophagia, palpitations due to atrial fibrillation, diffuse ST elevation on ECG and an increase in cardiac troponin. Coronary angiography was normal, cardiac MRI confirmed acute myocarditis. The evolution was favorable after a phase marked by supraventricular and ventricular rhythm disorders. The diagnostic and therapeutic challenge of this association are discussed, with a review of the literature.

Expression of integrin α4ß1 and α4ß7 on B cells correlates with autoimmune responses in Graves' disease.

BACKGROUND: Integrins are upregulated on endothelial cells and T-lymphocytes in autoimmune thyroid disease (AITD), potentially contributing to immune response localization. The role of integrins on B-cells in AITD remains unclear. METHODS: Peripheral blood samples were collected from healthy controls (n = 56), patients with Graves' disease (GD) (n = 37) and Hashimoto's thyroiditis (HT) (n = 52). Ultrasound-guided fine-needle aspiration (FNA) of the thyroid was performed in patients with non-autoimmune thyroid disease (nAITD) (n = 19), GD (n = 11), and HT (n = 40). Integrins α4ß7, α4ß1, and αEß7 in B cells were measured by flow cytometry. Serum zonulin levels were quantified via ELISA. Associations of integrins on B cells with thyroid hormones, thyroid autoantibodies, AITD duration, and zonulin were analyzed. RESULTS: HT patients exhibited lower α4ß7 and higher α4ß1 expression on B cells compared to healthy controls and GD patients. While α4ß7 was predominant on circulating B cells, the dominant integrin expressed on intrathyroidal B cells varied with specific thyroid diseases. In GD patients, α4ß7 and α4ß1 expression on circulating B cells correlated positively and negatively with thyroid function and thyroid stimulating immunoglobulins (TSI) levels, respectively. Intrathyroidal α4ß1+ B cells positively correlated with TSH levels in HT patients. Additionally, serum zonulin was elevated in HT patients, and intrathyroidal α4ß7+ B cells and α4ß1+ B cells correlated negatively and positively with zonulin levels, respectively. Integrin αEß7 on B cells showed no significant association with AITD. CONCLUSION: Integrins expressed on B cells potentially play a role in the pathogenesis of AITD and might serve as immune biomarkers for the disease.

Interaction of MMP-9 in the active phase of Graves' disease with and without ophthalmopathy.

Thyroid eye disease (TED) is expressed as orbital inflammation, and serum levels of several proinflammatory cytokines have been studied among patients with Graves' disease (GD) with and without TED; however, a more sensitive and specific marker for the different phases of GD and TED is still lacking. Seventeen active TED, 16 inactive TED, 16 GD without TED, and 16 healthy controls were recruited. Serum IL-17A, MMP-2, MMP-3, and MMP-9 were measured by multiplex bead assay. TED hormone and eye parameters were evaluated, and their relationship with cytokine levels was analyzed. Serum MMP-9 was higher in active TED than healthy controls, whereas IL-17A was lower among these patients than in GD without TED and healthy controls. No differences were found in MMP-3 and MMP-2 concentrations. MMP-9 levels were lower in patients with inactive TED who underwent radioactive iodine (RAI) therapy and those on levothyroxine replacement. MMP-9 levels were elevated in patients on methimazole. A negative correlation was found between age at assessment and time of follow-up with MMP-9 levels in inactive TED. Free T3 and ophthalmometry values were positively correlated with MMP-9 in the GD without TED and inactive TED groups, respectively. In conclusion, serum MMP-9 was increased in patients with active TED and was related to the RAI treatment, longer follow-up time, and higher ophthalmometry in patients with inactive TED, as well as thyroid function in GD without TED. MMP-9 may be involved in both the active phase of TED and the active phase of inflammation related to GD.NEW & NOTEWORTHY Our study addresses clinical aspects of specific ophthalmological examination and serum cytokine concentrations of patients with Graves' disease (GD) with and without ophthalmopathy. Our findings suggest that MMP-9 may be involved in the active phase of ophthalmopathy and in the active phase of GD. The central question is whether MMP-9 is a potential target for future treatments.

A comparative cross-sectional study on the quality of life in Grave's disease patients: urban vs. rural perspectives.

Grave's disease affects numerous patients globally, but its impact on health-related quality of life (HR-QoL) in relation to geographical disparities remains under-explored. This cross-sectional study aimed to assess the influence of urban versus rural residence on HR-QoL among patients diagnosed with Graves' Disease in Rajasthan, India. One hundred seven Graves' disease patients from rural and urban endocrine centers were analyzed. The rural group included 52 patients (24 males, 28 females), averaging 38.9 ± 10.9 years of age, while the urban group had 55 (13 males, 42 females) with an average age of 39.1 ± 14.2 years. We found differences between rural and urban patients in terms of gender ratio, BMI, smoking habits, and obesity. Multivariable linear regression was used in both groups to determine the association between the baseline characteristics of Graves' patients from both areas and HR-QOL. Health-related quality of life, assessed via the SF-36 questionnaire, indicated higher general health and role emotional scores among urban patients. Our study found that the duration of Graves' disease in rural centers negatively impacted physical health scores. In urban patients, age and BMI influenced physical health, while gender and disease duration affected mental health scores in rural patients. Age impacted mental health in urban patients. Rural patients had a poorer quality of life compared to urban patients. Differences in gender distribution, BMI, smoking habits, and obesity rates revealed disparities in Graves' disease between rural and urban patients in India, highlighting the need for better healthcare infrastructure and awareness in rural areas.

Nomogram construction and evaluation for predicting non-remission after a single radioactive iodine therapy for Graves' hyperthyroidism: a retrospective cohort study.

Background: Radioactive iodine (RAI) therapy is a widely used treatment for Graves' Hyperthyroidism (GH). However, various factors can impact the non-remission rate of GH after single RAI therapy. This study aimed to develop an online dynamic nomogram to assist physicians in providing personalized therapy for GH. Methods: Data from 454 GH patients who received RAI therapy were retrospectively reviewed and included in the present study. The univariate and multivariate analysis were conducted to investigate and identify independent influencing factors. The nomogram was developed based on the training cohort to explore non-remission rates. Finally, the reliability and accuracy of the constructed nomogram model were verified in the validation cohort via the calibration, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). Results: 24-hours radioactive iodine uptake (RAIU24h), effective half-life (Teff), total iodine dose (TID) and iodine dose per gram of thyroid tissue (IDPG) were independent predictors. The nomogram had a high C-index 0.922 (95% CI: 0.892-0.953), for predicting non-remission. The calibration curves demonstrated excellent consistency between the predicted and the actual probability of non-remission. ROC analysis showed that the AUC of the nomogram model and the four independent factors in the training cohort were 0.922, 0.673, 0.760, 0.761, and 0.786, respectively. The optimal cutoff value for the total nomogram scores was determined to be 155. A total score of ≥155 indicates a higher likelihood of non-remission after a single RAI therapy for GH, whereas a score below 155 suggests a greater likelihood of remission. Additionally, the DCA curve indicated that this nomogram had good clinical utility in predicting non-remission. Conclusion: An online nomogram was constructed with good predictive performance, which can be used as a practical approach to predict and assist physicians in making personalized therapy decisions for GH patients.

Type 2 hypersensitivity disorders, including systemic lupus erythematosus, Sjögren's syndrome, Graves' disease, myasthenia gravis, immune thrombocytopenia, autoimmune hemolytic anemia, dermatomyositis, and graft-versus-host disease, are THαß-dominant autoimmune diseases.

The THαß host immunological pathway contributes to the response to infectious particles (viruses and prions). Furthermore, there is increasing evidence for associations between autoimmune diseases, and particularly type 2 hypersensitivity disorders, and the THαß immune response. For example, patients with systemic lupus erythematosus often produce anti-double stranded DNA antibodies and anti-nuclear antibodies and show elevated levels of type 1 interferons, type 3 interferons, interleukin-10, IgG1, and IgA1 throughout the disease course. These cytokines and antibody isotypes are associated with the THαß host immunological pathway. Similarly, the type 2 hypersensitivity disorders myasthenia gravis, Graves' disease, graft-versus-host disease, autoimmune hemolytic anemia, immune thrombocytopenia, dermatomyositis, and Sjögren's syndrome have also been linked to the THαß pathway. Considering the potential associations between these diseases and dysregulated THαß immune responses, therapeutic strategies such as anti-interleukin-10 or anti-interferon α/ß could be explored for effective management.

Familial hypokalemic periodic paralysis: a case induced by concurrent hyperthyroidism.

BACKGROUND: Familial hypokalemic periodic paralysis (HypoPP) is an uncommon genetic disorder characterized by recurrent episodes of muscle weakness and hypokalemia, typically starting in early adulthood. The existence of hyperthyroidism in the presence of HypoPP is more strongly associated with a diagnosis of thyrotoxic periodic paralysis (TPP), with most cases occurring in Asian males with pathogenic KCNJ2 or KCNJ18 variants and without a family history of the condition. This case is novel due to the combination of familial HypoPP and hyperthyroidism induced by Graves' disease, a rare occurrence especially in non-Asian populations. CASE PRESENTATION: A 40-year-old African American man presented with profound muscle weakness after consuming a high-salt meal. He had a significant family history of hyperthyroidism and hypokalemia. On examination, he showed profound weakness in all extremities. Laboratory tests confirmed hypokalemia and hyperthyroidism, and genetic testing identified a pathogenic variant in the CACNA1S gene (c.1583 G > A, p. R528H), with normal SCN4A, KCNJ2 and KCNJ18 sequencing. He was diagnosed with familial HypoPP and hyperthyroidism due to Graves' disease. He was started on PO methimazole 10 mg three times a day and PO acetazolamide 250 mg twice a day. He was advised to follow a low carbohydrate and low salt diet. CONCLUSIONS: This case highlights the importance of considering a genetic basis for HypoPP in patients with a family history of the condition, even when hyperthyroidism is present. The combination of familial HypoPP and Graves' disease is rare and emphasizes the need for careful genetic and clinical evaluation in similar cases. Management should focus on correcting hypokalemia, treating hyperthyroidism, and lifestyle modifications to prevent recurrence.

Efficacy of selenium supplementation for patients with Graves' hyperthyroidism during methimazole treatment: protocol for a systematic review and meta-analysis.

INTRODUCTION: The most common cause of hyperthyroidism, Graves' disease is a common organ-specific autoimmune disease. Selenium is an essential trace element of the human body that is mainly concentrated in the thyroid gland and is involved in the synthesis and metabolism of thyroid hormones. Most studies have shown that the level of selenium is closely related to the occurrence and development of thyroid diseases, and selenium supplementation can help improve thyroid function. This study aims to evaluate the efficacy of selenium supplementation for patients with Graves' hyperthyroidism during methimazole treatment. METHODS AND ANALYSIS: We will search the electronic databases including PubMed, Web of Science, Embase, the Cochrane Library, China National Knowledge Infrastructure, Wanfang Data and Chinese Biomedical Literature, and the time was deadline to December 2023. To evaluate the efficacy of methimazole combined with selenium supplementation in the treatment of Graves' hyperthyroidism, randomised controlled trials will be included. The Cochrane Collaboration's risk of bias tool will be used to assess the quality of all included studies, and the baseline data of all the studies are extracted by the authors. A random-effects model or a fixed-effects model is used to analyse the outcomes. The primary outcomes are the levels of selenium, triiodothyronine, free thyroxine and thyroid-stimulating hormone (TSH), whereas the secondary outcomes include TSH receptor antibody, thyroid peroxidase antibody and thyroglobulin antibody. ETHICS AND DISSEMINATION: Ethics approval is not required since no original data will be collected. The results of this study will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023410999.

Efficacy of Anti-Thyroid Medications in Patients with Graves' Disease.

INTRODUCTION: Graves' disease (GD) is an autoimmune disorder characterized by hyperthyroidism due to increased thyroid-stimulating hormone receptor antibodies (TRAb).The treatment of GD often consists of radioactive iodine therapy, anti-thyroid drugs (ATD), or thyroidectomy. Since few studies have collected data on remission rates after treatment with ATD in Saudi Arabia, our study aimed to assess the efficacy and the clinical predictors of GD long-term remission with ATD use. METHOD: We conducted a retrospective chart review study of 189 patients with GD treated with ATD between July 2015 and December 2022 at the endocrine clinics in King Abdulaziz Medical City in Riyadh. All GD patients, adults, and adolescents aged 14 years and older who were treated with ATD during the study period and had at least 18 months of follow-up were included in the study. Patients with insufficient follow-up and those who underwent radioactive iodine (RAI) therapy or thyroidectomy as first-line therapy for GD were excluded from the study. RESULTS: The study sample consisted of 189 patients, 72% of whom were female. The patients' median age was 38years (33, 49). A total of 103 patients (54.5%) achieved remission. The median follow-up period for the patients was 22.0 months (9, 36). Patients who achieved remission had lower mean free T4 levels (25.8pmol/l ± 8.93 versus 28.8pmol/l ± 10.82) (P value = 0.038) and lower median TRAb titer (5.1IU/l (2.9, 10.7)) versus (10.5IU/l (4.2, 22.5)) (P value = 0.001) than patients who did not achieve remission. Thirty-five out of 103 patients who achieved remission (34%) relapsed after ATD discontinuation. The patients who relapsed showed higher median thyroid uptake on 99mTc-pertechnetate scan than patients who did not relapse: 10.3% (5.19, 16.81) versus 6.0% (3.09, 12.38), with a P value of 0.03. They also received ATD for a longer period, 40.0 months (29.00, 58.00) versus 25.0 months (19.00, 32.50), with a P value of < 0.0001. CONCLUSION: The remission of GD was achieved in approximately half of the patients treated with ATD; however, approximately one-third of them relapsed. Lower Free T4 and TRAb levels at diagnosis were associated with remission. Longer ATD use and higher thyroid uptake upon diagnosis were associated with relapse after ATD discontinuation. Future studies are necessary to ascertain the predictors of ATD success in patients with GD.

T-cell exhaustion-related genes in Graves' disease: a comprehensive genome mapping analysis.

Background: T-cell exhaustion (Tex) can be beneficial in autoimmune diseases, but its role in Graves' disease (GD), an autoimmune disorder of the thyroid, remains unknown. This study investigated Tex-related gene expression in GD patients to discern the potential contributions of these genes to GD pathogenesis and immune regulation. Methods: Through gene landscape analysis, a protein-protein interaction network of 40 Tex-related genes was constructed. mRNA expression levels were compared between GD patients and healthy control (HCs). Unsupervised clustering categorized GD cases into subtypes, revealing distinctions in gene expression, immune cell infiltration, and immune responses. Weighted gene co-expression network analysis and differential gene expression profiling identified potential therapeutic targets. RT-qPCR validation of candidate gene expression was performed using blood samples from 112 GD patients. Correlations between Tex-related gene expression and clinical indicators were analyzed. Results: Extensive Tex-related gene interactions were observed, with six genes displaying aberrant expression in GD patients. This was associated with atypical immune cell infiltration and regulation. Cluster analysis delineated two GD subtypes, revealing notable variations in gene expression and immune responses. Screening efforts identified diverse drug candidates for GD treatment. The Tex-related gene CBL was identified for further validation and showed reduced mRNA expression in GD patients, especially in cases of relapse. CBL mRNA expression was significantly lower in patients with moderate-to-severe thyroid enlargement than in those without such enlargement. Additionally, CBL mRNA expression was negatively correlated with the disease-specific indicator thyrotropin receptor antibodies. Conclusion: Tex-related genes modulate GD pathogenesis, and their grouping aids subtype differentiation and exploration of therapeutic targets. CBL represents a potential marker for GD recurrence.