Assessing the relationship between psoriasis and thyroid dysfunction through two sample MR analysis.

BACKGROUND: The association between psoriasis and hyperthyroidism/hypothyroidism remains inconclusive, with conflicting findings in prior studies. OBJECTIVES: This study employs Mendelian randomization methods to assess the potential relationship. METHODS: Given the inability to accurately observe the link between psoriasis and thyroid dysfunction, we prioritized utilizing known genetic variants to investigate the potential impacts of the disease.We analyzed data from genome-wide association studies (GWASs), FinnGen, and UK Biobank to extract information on psoriasis, hyperthyroidism, and hypothyroidism. Three MR approaches (MR Egger, weighted median, and inverse variance weighted) were used to scrutinize the causal link. RESULTS: Our analysis revealed no correlation between psoriasis and hyperthyroidism/hypothyroidism. However,  vulgar psoriasis and guttate psoriasis were associated with hypothyroidism/myxedema (IVW odds ratio (OR) = 1.00, 95% confidence interval (CI) = 1.00-1.00, P = 2.53E-03), and Graves' disease (IVW OR = 0.86, 95% CI = 0.72-1.01, P = 4.75E-02).In a subsequent analysis, we observed that hypothyroidism with mucinous edema showed no correlation with Graves' disease in the opposite(P = 9.33E-01). CONCLUSION: This MR analysis suggests no association between psoriasis and thyroid dysfunction, but highlights associations of vulgar/guttate psoriasis with hypothyroidism/myxedema and Graves' disease. In clinical practice, diagnosing guttate psoriasis requires vigilance for associated risks from hypothyroidism and Graves' disease. For patients with both vulgar psoriasis and hypothyroidism, careful monitoring for mucinous edema is crucial, as it may signal a hypothyroid crisis.

Global research landscape and emerging trends in Graves' disease: A bibliometric analysis.

BACKGROUND: Graves' disease is a prevalent thyroid disorder and is the primary cause of hyperthyroidism. Significant progress has been made in understanding the epidemiology, pathogenesis, diagnosis, treatment, and prognosis of this disease. However, bibliometric analyses on Graves' disease are lacking. We aimed to comprehensively summarize the research, progression, and focal points of Graves' disease through data mining and integrated analysis of the existing literature. METHODS: We retrieved relevant literature on Graves' disease from 2003 to 2023 from the Web of Science database. We performed bibliometric analysis using CiteSpace and the R package Bibliometrix. RESULTS: We identified 10,901 publications from 132 countries, with a steady rise in the number of publications over the past 5 years. The US leads in publication volume, with the University of California System being the primary contributing institution. The journal Thyroid had the highest publication output, while the Journal of Clinical Endocrinology and Metabolism was the most frequently cited. These publications involved 2305 authors, with Antonelli Alessandro and Smith Terry being the most prolific. The most frequently cited articles were the "2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis" and the "Thyroid Association/European Group on Graves' orbitopathy guidelines for the management of Graves' orbitopathy." Analysis of the bursts of cited references, keywords, and their clustering revealed that research on Graves' disease predominantly centers on clinical management, thyroid-stimulating hormone receptors, thyroid hormones, autoimmunity and inflammation, Graves' ophthalmopathy, thyroid nodules, and thyroid cancer. CONCLUSION: This is the first comprehensive bibliometric study to summarize progress and trends in Graves' disease research. These results highlight recent research hotspots and promising directions, thereby providing a valuable reference for other scholars.

Thyroiditis and COVID-19: focus on pediatric age. A narrative review.

PURPOSE: In light of the growing concern over the possible link between SARS-CoV2 infection and autoimmune diseases, we conducted a review to investigate the impact of the pandemic outbreak on thyroid diseases. METHODS: We carried out a narrative review of all pediatric cases described in the literature, mainly focusing on the possible association of COVID-19 with the incidence of autoimmune and post-infective thyroid diseases (namely Hashimoto's Thyroiditis (HT), Grave's Disease (GD) and Sub-Acute Thyroiditis (SAT)). We also felt it was necessary to provide a brief review of Non-thyroidal Illness Syndrome (NTIS) and Multisystem Inflammatory Syndrome in Children (MIS-C) because of their overlap with thyroiditis. RESULTS: There is currently no conclusive evidence linking SARS-CoV-2 infection with an increased incidence of autoimmune thyroiditis (AT) in pediatric age. However, SAT may be a mild complication of SARS-CoV-2 infection, as is the case with other viral infections. SAT typically resolves on its own and does not require treatment. NTIS may be associated with inflammatory complications, such as MIS-C, and admission to intensive care. It may also be considered a prognostic risk factor for severe disease. The hypothesized pathogenetic mechanisms of thyroid damage in COVID-19 include direct damage due to the significant expression of angiotensin-converting enzyme 2 (ACE2) in the thyroid gland, which is a ligand for the virus, and indirect damage due to immune dysregulation, such as the overproduction of IL-6, which is thought to be part of the pathogenesis of thyroiditis. CONCLUSION: However, due to the limited evidence available, further prospective longitudinal studies are required to clarify the relationship between COVID-19 and thyroid disease in children and adolescents, as well as to investigate any potential long-term consequences.

GRADE-ADOLOPMENT of hyperthyroidism treatment guidelines for a Pakistani context.

INTRODUCTION: The prevalence of hyperthyroidism in Pakistan is 2.9%, which is two times higher than in the United States. Most high-quality hyperthyroidism clinical practice guidelines (CPGs) used internationally originate from high-income countries in the West. Local CPGs in Pakistan are not backed by transparent methodologies. We aimed to produce comprehensive, high-quality CPGs for the management of hyperthyroidism in Pakistan. METHODS: We employed the GRADE-ADOLOPMENT approach utilizing the 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis as the source CPG. Recommendations from the source guideline were either adopted as is, excluded, or adapted according to our local context. RESULTS: The source guideline included a total of 124 recommendations, out of which 71 were adopted and 49 were excluded. 4 recommendations were carried forward for adaptation via the ETD process, with modifications being made to 2 of these. The first addressed the need for liver function tests (LFTs) amongst patients experiencing symptoms of hepatotoxicity while being treated with anti-thyroid drugs (ATDs). The second pertained to thyroid status testing post-treatment by radioactive iodine (RAI) therapy for Graves' Disease (GD). Both adaptations centered around the judicious use of laboratory investigations to reduce costs of hyperthyroidism management. CONCLUSION: Our newly developed hyperthyroidism CPGs for Pakistan contain two context-specific modifications that prioritize patients' finances during the course of hyperthyroidism management and to limit the overuse of laboratory testing in a resource-constrained setting. Future research must investigate the cost-effectiveness and risk-benefit ratio of these modified recommendations.

Incidental but Not Insignificant: Thyroid Cancer in Patients with Graves Disease.

BACKGROUND: Graves disease is the most common cause of hyperthyroidism in the US. Treatment with antithyroid drugs and radioactive iodine is more commonly used than surgical management with total thyroidectomy (TTx). However, incidentally discovered thyroid cancer (TC) has been described on surgical pathology from patients who underwent surgical treatment of Graves disease, which would be missed with these other treatment strategies. We sought to determine the incidence rate of TC among patients with surgically treated Graves disease. STUDY DESIGN: We retrospectively reviewed patients with Graves disease who underwent TTx at a single institution from 2011 to 2023. Pathology reports were reviewed for TC. Patient demographics, preoperative laboratory and radiological evaluations, preoperative medical management, and surgical outcomes were compared between patients with and without incidental TC. RESULTS: There were 934 patients, of whom 60 (6.4%) patients had incidentally discovered TC on pathology. The majority (58.3%) of patients had papillary thyroid carcinoma, followed by 33.3% with papillary microcarcinoma. Preoperative ultrasound (US) was obtained in 564 (60.4%) of patients, with 44.3% with nodules, but only 34 (13.7%) of those with nodules had TC on final pathology. Preoperative fine needle aspiration was obtained in 15 patients with TC, and 8 patients (53.3%) were reported as benign lesions, which ultimately had TC on final pathology. There was no difference in sex, race or ethnicity, preoperative medical management, and postoperative outcomes between the 2 groups. CONCLUSIONS: Incidental TC was found on surgical pathology in 6.4% of patients undergoing TTx for Graves disease. Preoperative imaging with US and fine needle aspiration were often unreliable at predicting TC. The incidence of TC should not be underestimated when counseling patients on definitive management for Graves disease.

Prevalence, Risk Factors, and Clinical and Biochemical Characteristics of Alemtuzumab-Induced Graves Disease.

OBJECTIVE: Atypical Graves disease (GD) is a common complication in multiple sclerosis (MS) patients treated with alemtuzumab. We present epidemiological, clinical, and biochemical characteristics of alemtuzumab-induced GD. METHODS: Retrospective follow-up study of MS patients treated with alemtuzumab from 2014 to 2020, including clinical course of GD, pregnancy outcome, and thyroid eye disease (TED). RESULTS: We enrolled 183 of 203 patients (90%, 68% women) treated with alemtuzumab at 4 hospitals in Norway. Seventy-five (41%) developed thyroid dysfunction, of whom 58 (77%) had GD. Median time from the first dose of alemtuzumab to GD diagnosis was 25 months (range, 0-64). Twenty-four of 58 GD patients (41%) had alternating phases of hyper- and hypothyroidism. Thyrotropin receptor antibodies became undetectable in 23 of 58 (40%) and they could discontinue antithyroid drug treatment after a median of 22 (range, 2-58) months. Conversely, 26 (44%) had active disease during a median follow-up of 39 months (range, 11-72). Two patients (3%) received definitive treatment with radioiodine, 6 (10%) with thyroidectomy. Nine developed TED (16%), 7 had mild and 2 moderate to severe disease. Four patients completed pregnancy, all without maternal or fetal complications. Patients who developed GD had a lower frequency of new MS relapses and MRI lesions than those without. CONCLUSION: GD is a very common complication of alemtuzumab treatment and is characterized by alternating hyper- and hypothyroidism. Both remission rates and the prevalence of TED were lower than those reported for conventional GD. Pregnancies were uncomplicated and GD was associated with a lower risk of subsequent MS activity.

Graves' Disease Following COVID-19 Vaccination: A Population-based, Matched Case-control Study.

OBJECTIVE: Multiple cases and case series reported Graves' disease (GD) following coronavirus disease 2019 (COVID-19) vaccination. We aimed to determine whether COVID-19 vaccination was associated with the incidence of GD. METHODS: We analyzed data from Clalit Health Services, the largest healthcare organization in Israel, which insures 4.7 million patients. A population-based, matched, case-control study was performed. Cases were defined as adult patients diagnosed with GD between December 2020 and November 2022. Each case was matched with controls in a 1:2 ratio. Each control was assigned an index date, which was identical to that of their matched case, defined as the date of GD diagnosis. Time between vaccination date and the diagnosis of GD or index date was assessed. RESULTS: A total of 726 patients with GD were matched with 1452 controls. The study patients and controls have received similar proportions of the COVID-19 vaccine [at least 1 dose: 80% (581/726) vs 77.8% (1129/1452), P = .22, respectively]. In a univariate analysis, at least 1 dose of the COVID-19 vaccine was not associated with the incidence of GD [odds ratio 95% confidence interval: 1.15 (.92-1.43)]. The mean time between first COVID-19 vaccination and the diagnosis of GD for cases or index date for controls was not significantly different [275.69 days (SD 144.37) for cases compared to 275.45 days (SD 145.76) for controls]. CONCLUSION: Our study found no association between COVID-19 vaccination and the incidence of GD.

Alemtuzumab induces severe orbitopathy in relapsing-remitting multiple sclerosis.

CONTEXT: Treatment with Alemtuzumab (ALZ) in patients with Relapsing-Remitting Multiple Sclerosis (RRMS) is associated with the development of ALZ-induced Graves' disease (GD-ALZ). Some cases may develop associated Graves´ Orbitopathy (GO-ALZ), with possible visual compromise. AIM: The aim of this study was to describe the main clinical and biochemical characteristics of GD-ALZ, as well as the clinical course of a case series of GO-ALZ METHODS: This study is a retrospective observational study, carried out in a reference hospital for the care of patients with RRMS in Spain. Cases treated with ALZ in the period 2014-2022 were included. GO-ALZ cases were identified among those with clinical symptoms compatible with thyroid eye disease after initiating ALZ treatment. RESULTS: A total of 135 cases, with a mean follow-up of 69.6 months after the first ALZ cycle, were included. The incidence of GD-ALZ was 32.6% (44/135), with a predominance of women (77.3%) and mean age of 41.9 years. The presence of first-degree relatives with hypothyroidism was identified as risk factor for the development of GD-ALZ (adjusted P-value: 0.02). GO-ALZ was diagnosed in 6 cases (incidence: 13.6%), of which 3 had severe clinical forms of GO, requiring anti-IL-6 treatment. A favorable response was reported in all of them, with a significant decrease in disease activity and improvement in proptosis. CONCLUSIONS: We report one of the largest cohorts of GD-ALZ and GO-ALZ cases. The diagnosis of these entities should be taken into account in patients treated with Alemtuzumab, given the risk of developing severe clinical forms. In moderate-severe forms of GO-ALZ, drugs with anti-IL-6 activity are a safe and effective option.

Association Between Eight Autoimmune Diseases and Thyroid Cancer: A Nationwide Cohort Study.

Background: It has often been reported that thyroid-specific autoimmune diseases (ADs), such as Hashimoto's thyroiditis and Graves' disease, could increase the risk of thyroid cancer, but the association between other ADs beyond thyroid and thyroid cancer has not been well investigated. This study aimed to examine the risk of thyroid cancer in patients with eight ADs compared with those without ADs. Methods: This nationwide retrospective matched cohort study was conducted to investigate the relationship of eight ADs (Hashimoto's thyroiditis, Graves' disease, type 1 diabetes mellitus, Sjogren's disease, inflammatory bowel disease [IBD], vitiligo, systemic lupus erythematosus, and rheumatoid arthritis [RA]) with the risk of incident thyroid cancer using the National Health Insurance Service-National Sample Cohort. The Cox-proportional hazard model was used to estimate the adjusted hazard ratio (HR) and confidence intervals (CI) for thyroid cancer in relation to each of AD compared with control group without AD. Results: During the average follow-up of 9.49 years, 138 thyroid cancer cases were newly developed in control group and 268 cases were occurred in group with 8 ADs. For all of study participants, the risk of thyroid cancer was significantly increased in patients with Hashimoto's thyroiditis (HR = 2.10 [1.57-2.81]), Graves' disease (HR = 2.67 [1.99-3.62]), IBD (HR = 2.06 [1.50-2.83]), vitiligo (HR = 1.71 [1.13-2.59]), RA (HR = 1.76 [1.07-2.90]), and total of 8 ADs (HR = 1.97 [1.60-2.42]) compared with control group without ADs. When ADs were divided into three types, thyroid-specific ADs (HR = 2.37 [1.85-3.03]) showed the strongest and significant association with thyroid cancer, followed by local ADs (HR = 1.83 [1.41-2.38]), and systemic ADs (HR = 1.77 [1.14-2.74]). Conclusions: Specific ADs-especially for thyroid-specific AD, vitiligo, IBD, and RA-were associated with increased risk for thyroid cancer.

Transition from Hashimoto thyroiditis to Graves's Disease: an unpredictable change?

PURPOSE: Hashimoto thyroiditis and Graves's disease are two related autoimmune disorders, representing the leading causes of hypothyroidism and hyperthyroidism. Autoimmune hypothyroidism is generally irreversible but very rarely, some patients would shift to hyperthyroidism. The aim of the study was to seek for possible clinical predictors of the transition from hypo to hyperthyroidism in patients with Hashimoto thyroiditis and to outline their clinical phenotype. METHODS: Twelve patients with overt autoimmune hypothyroidism who had at least one transition from hypothyroidism to autoimmune hyperthyroidism were compared with 294 consecutive patients with autoimmune hypothyroidism and 69 consecutive patients with autoimmune hyperthyroidism that accessed the outpatient clinic over six months. Demographic, hormonal data and autoantibodies titers were compared. RESULTS: Prevalence of smoking habit was significantly higher in switchers compared to controls. Switchers showed a significantly higher prevalence of personal and familial history of non-thyroidal autoimmune disorders. TSH levels were significantly lower in the switcher group during the hypothyroid phase and levothyroxine dose required was lower. TSH concentrations were significantly lower while free fT4 and free fT3 values were higher in GD patients compared to switchers during the hyperthyroid phase despite comparable TRAb levels. Prevalence and type of hyperthyroid symptoms and orbitopathy were similar between switchers and GD group. Mean dose of anti-thyroid drugs was significantly higher in GD patients compared to switchers. No differences were observed in the remission rate from hyperthyroidism between the two groups, despite switchers showed a significantly lower time-to-remission. CONCLUSIONS: Conversion of Hashimoto Thyroiditis towards Graves' disease is a rare phenomenon which can occur almost at any time after the development of autoimmune hypothyroidism. Our findings suggest active surveillance of hypothyroid patients who require frequent reduction of levothyroxine during follow up and testing for TSHR antibodies in these patients.

New insight into the causal relationship between Graves' disease liability and drug eruption: a Mendelian randomization study.

Background: Graves' disease (GD) and drug eruption are closely associated and frequently observed in the clinical setting. However, it remains unclear whether a causal relationship exists between these two conditions. The aim of the study is to investigate whether GD is causal to drug eruptions using two-sample Mendelian randomization. Methods: We launched a two-sample MR to investigate whether GD is causal to drug eruption using Genome-wide association study (GWAS) summary data from Biobank Japan and FinnGen. Genetic variants were used as instrumental variables to avoid confounding bias. Statistical methods including inverse variance weighted (IVW), weighted median, MR-Egger, and MR-PRESSO were conducted to identify the robustness of the causal effect. Results: Genetically predicted GD may increase the risk of drug eruption by 30.3% (OR=1.303, 95% CI 1.119-1.516, p<0.001) in the Asian population. In European populations, GD may increase the generalized drug eruption by 15.9% (OR=1.159, 95%CI 0.982-1.367, p=0.080). Conclusions: We found GD is potentially causal to drug eruption. This finding expanded the view of the frequently observed co-existence of GD and adverse drug reactions involving the skin. The mechanism remains for further investigation.

Fracture Incidence in Graves' Disease: A Population-Based Study.

Background: Population-based studies have indicated an increase in bone turnover in hyperthyroidism with a subsequent decrease in bone mineral density and an increased risk of fractures, especially in postmenopausal women. However, heterogeneity between studies prevents a definitive conclusion. Graves' disease (GD) is an autoimmune disease, and it is the most common cause of hyperthyroidism. The aim of this study was to investigate fracture risk in patients with GD. Methods: A total of 2134 patients with incident GD and 21,261 age, sex- and county-matched controls were included 16-18 years after diagnosis in a retrospective cohort study. Drug and patient national registries in Sweden were used to assess the risk of developing skeletal complications. Up to 10 years of age, sex- and county-matched controls per patient were selected from databases from the National Board of Health and Welfare and Statistics Sweden. Cox proportional hazards models were fitted to estimate hazard ratios (HR) and confidence intervals [CI]. Results: There were no significant differences in fracture rates between GD and controls but after adjustment for comorbidities, the data showed higher vertebral fracture rates in male GD patients aged >52 years compared to male controls, HR = 2.83 [CI 1.05-7.64]. The rates of osteoporosis treatments as well as treatment with corticosteroids were higher in patients with GD. However, HR for the association between GD and fractures remained largely unchanged after adjustment for osteoporosis treatments and treatments with corticosteroids. Conclusions: There were no significant differences in total fracture rate between GD and the general population. However, men older than 52 years had a higher vertebral fracture rate. This study also shows that patients with treated GD receive more osteoporosis treatments compared to the general population.

Incidence and risk factors for Graves' orbitopathy in patients who underwent anti-inflammatory and immunosuppressive treatment during medical treatment for Graves' disease: investigation of 1,553 cases with newly diagnosed Graves' disease and proposal of a predictive score.

Appropriate administration of anti-inflammatory and immunosuppressive treatment (AIIST) is important for patients with Graves' orbitopathy (GO). This study aimed to clarify the incidence and risk factors for GO treated with AIIST and propose a predictive score, among newly diagnosed Graves' disease (GD) patients in Japan. A total of 1,553 GD patients who were newly diagnosed during the year 2011 were investigated. AIIST included local and/or systemic glucocorticoid administration and retrobulbar irradiation. A multivariable Cox proportional hazards model was used to investigate the risk factors for GO underwent AIIST during medical treatment, including at diagnosis, of GD. Then, a GO score was created by summing each point assigned to risk factors based on their coefficient obtained in the Cox model. AIIST was administered to 107 patients (6.9%). The risk factors and hazard ratios for GO underwent AIIST were: age (per 10 years), 1.32 (95% confidence interval: 1.16-1.50), p < 0.0001; TSH binding inhibitory immunoglobulin (TBII) (per 10 IU/L), 1.33 (1.15-1.54), p = 0.0001; and thyroglobulin antibody (TgAb) negativity, 2.98 (1.96-4.59), p < 0.0001. The GO score, ranging from 0 to 8 points, showed moderate performance (area under the curve: 0.71, cut-off value: 5 points, sensitivity: 0.76, specificity: 0.59, positive predictive value: 0.12, negative predictive value: 0.97). AIIST was performed for patients with active manifestations of GO in 6.9% of newly diagnosed GD patients. The risk factors for GO underwent AIIST were higher age, higher TBII, and TgAb negativity. The GO score based on these factors may be useful in managing GO.

New-onset and relapsed Graves' disease following COVID-19 vaccination: a comprehensive review of reported cases.

Global Coronavir us disease 2019 (COVID-19) vaccination efforts are being intensified to combat the pandemic. As the frequency of immunization against COVID-19 has increased, some adverse effects related to vaccination have emerged. Within this context, this article reviewed 62 Graves' disease (GD) cases following COVID-19 vaccination, to probe the potential association between the vaccination and the onset of GD. A comprehensive search of the PubMed, Web of Science, and Scopus databases was conducted to collect GD cases following COVID-19 vaccination up to June 7, 2023. Among the 62 GD cases included in this review, there were 33 (53.2%) new-onset GD and 10 (16.1%) relapsed GD patients following mRNA vaccination, 14 (22.6%) new-onset GD and 4 (6.5%) relapsed GD patients following viral vector vaccination, and 1 (1.6%) relapsed GD patients following inactivated vaccination. Median durations to symptoms onset for new-onset and relapsed GD were 12 (range: 1-60) and 21 (range: 5-30) days following mRNA vaccination, while 7 (range: 1-28) and 14 (range: 10-14) days following viral vector vaccination, respectively. While the definitive pathogenesis of GD following COVID-19 vaccination remains unclear, it might be associated with cross-immune responses triggered by molecular mimicry, and an adjuvant-induced autoimmune/inflammatory syndrome. However, due to the limited number of observed GD cases following COVID-19 vaccination and the lack of systematic experimental studies, a causal relationship between COVID-19 vaccination and the onset of GD has not been definitively confirmed. It should be highlighted that most of GD patients following COVID-19 vaccination experienced positive outcomes after treatment. In the broader context of ending the COVID-19 pandemic and reducing mortality rates, the benefits of COVID-19 vaccination significantly outweigh mild risks such as treatable GD. Adherence to the COVID-19 vaccination schedule is therefore imperative in effectively managing the pandemic.

The Incidence of Graves' Hyperthyroidism Before and After COVID-19 Messenger RNA Vaccination.

OBJECTIVE: Case reports of postvaccine early-onset Graves' hyperthyroidism (PVGD) after the administration of COVID-19 vaccination have emerged. Our aim was to investigate whether the incidence of Graves' hyperthyroidism (GD) has increased after the introduction of COVID-19 vaccination. METHODS: We compared the incidence of new-onset GD at a single academic center during 2 periods: December 2017 to October 2019 and December 2020 to October 2022, ie, before and after the implementation of COVID-19 vaccinations. We defined PVGD as laboratory-confirmed hyperthyroidism and GD within 4 weeks after the vaccination or clear onset of symptoms of thyrotoxicosis within 4 weeks of vaccination with evidence of hyperthyroidism and GD within 3 months. RESULTS: During the prevaccination period, 803 patients carried diagnoses of GD, and of these, 131 were new. During the postvaccination period, 901 patients carried diagnoses of GD, and of these, 138 were new. There was no statistically significant difference in the incidence of GD (P = .52), age at onset, gender, or race between the 2 groups. Twenty-four of 138 newly diagnosed patients in the post-COVID-19 group met the criteria for PVGD. The median free T4 was higher, but this was not statistically significant (3.9 vs 2.5 ng/dL, P = .05). There were no differences in age, gender, race, antibody titers, or type of vaccination between PVGD and controls. CONCLUSION: There was no increase in new-onset GD after COVID-19 vaccination. Median free T4 was higher in patients with PVGD, but this was not statistically significant.

Graves' disease as a driver of depression: a mechanistic insight.

Graves' disease (GD) is characterized by diffuse enlargement and overactivity of the thyroid gland, which may be accompanied by other physical symptoms. Among them, depression can dramatically damage patients' quality of life, yet its prevalence in GD has not received adequate attention. Some studies have established a strong correlation between GD and increased risk of depression, though the data from current study remains limited. The summary of mechanistic insights regarding GD and depression has underpinned possible pathways by which GD contributes to depression. In this review, we first summarized the clinical evidence that supported the increased prevalence of depression by GD. We then concentrated on the mechanistic findings related to the acceleration of depression in the context of GD, as mounting evidence has indicated that GD promotes the development of depression through various mechanisms, including triggering autoimmune responses, inducing hormonal disorders, and influencing the thyroid-gut-microbiome-brain axis. Finally, we briefly presented potential therapeutic approaches to decreasing the risk of depression among patients with GD.

Sex-specific risk factors associated with graves' orbitopathy in Korean patients with newly diagnosed graves' disease.

OBJECTIVE: To assess sex-specific risk factors for Graves' orbitopathy (GO) in newly diagnosed Graves' disease (GD) patients. METHODS: A retrospective cohort study was conducted using the National Health Insurance Service's sample database, which consisted of 1,137,861 subjects from 2002 to 2019. The international classification of disease-10 codes was used to identify those who developed GD (E05) and GO (H062). A multivariable Cox proportional hazards model was used to estimate the effect of risk factors on GO development. RESULTS: Among 2145 male and 5047 female GD patients, GO occurred in 134 men (6.2%) and 293 women (5.8%). A multivariable Cox regression model revealed that GO development was significantly associated with younger age (HR = 0.84, 95% CI = 0.73-0.98), low income (HR = 0.55, 95% CI = 0.35-0.86), and heavy drinking (HR = 1.79, 95% CI = 1.10-2.90) in men, and with younger age (HR = 0.89, 95% CI = 0.81-0.98), lower body mass index (HR = 0.55, 95% CI = 0.33-0.90), high total cholesterol (HR = 1.04, 95% CI = 1.01-1.06), hyperlipidaemia (HR = 1.37, 95% CI = 1.02-1.85), and lower statin dose (HR = 0.37, 95% CI = 0.22-0.62) in women. There was no association between smoking and GO development in both men and women. CONCLUSIONS: The risk factors for GO development were sex-dependent. These results show the need for more sophisticated attention and support considering sex characteristics in GO surveillance.

How Does Vitamin D Affect Immune Cells Crosstalk in Autoimmune Diseases?

Vitamin D is a secosteroid hormone that is highly involved in bone health. Mounting evidence revealed that, in addition to the regulation of mineral metabolism, vitamin D is implicated in cell proliferation and differentiation, vascular and muscular functions, and metabolic health. Since the discovery of vitamin D receptors in T cells, local production of active vitamin D was demonstrated in most immune cells, addressing the interest in the clinical implications of vitamin D status in immune surveillance against infections and autoimmune/inflammatory diseases. T cells, together with B cells, are seen as the main immune cells involved in autoimmune diseases; however, growing interest is currently focused on immune cells of the innate compartment, such as monocytes, macrophages, dendritic cells, and natural killer cells in the initiation phases of autoimmunity. Here we reviewed recent advances in the onset and regulation of Graves' and Hashimoto's thyroiditis, vitiligo, and multiple sclerosis in relation to the role of innate immune cells and their crosstalk with vitamin D and acquired immune cells.

Incidence, Risk Factors, and Outcomes of Incident Atrial Fibrillation in Patients With Graves Disease.

OBJECTIVE: To describe the incidence, risk factors, and outcomes of incident atrial fibrillation (AF) in Graves disease (GD). PATIENTS AND METHODS: Patients with GD between January 1, 2009, and December 31, 2019, were included retrospectively. We defined GD-related AF as AF diagnosed less than or equal to 30 days before or any time after GD. Late-onset AF was defined as incident AF diagnosed more than 90 days after GD. RESULTS: Of 1371 patients with GD, AF occurred in 139 patients. Late-onset AF occurred in 32 (23.0%) of AF cases, of which 16 (50.0%) had attained euthyroidism. Independent risk factors were age (HR, 1.05; 95% CI, 1.03-1.06 per year), overt hyperthyroidism (free T4 >1.7 ng/dL; HR, 2.75; 95% CI, 1.38 to 5.46), and male sex (HR, 2.30; 95% CI, 1.54 to 3.43) for early AF. These were age (HR, 1.08; 95% CI, 1.05 to 1.119 per year), chronic obstructive pulmonary disease (HR, 3.47; 95% CI, 1.36 to 5.54), and heart failure (HR, 5.86; 95% CI, 2.39 to 14.38) for late AF. Atrial fibrillation in GD was associated with higher mortality (HR, 16.32; 95% CI, 4.66 to 56.58), acute coronary syndrome/stable angina events (HR, 3.89; 95% CI, 1.23 to 12.31), and cardiac hospitalizations (HR, 15.39; 95% CI, 8.17 to 29.00) when adjusted to age, sex, and pre-existing AF. CONCLUSION: Late-onset AF comprised one-quarter of GD-related AF cases requiring surveillance even after restoring euthyroidism. Risk factors for AF in GD are similar to those in the general population although overt hyperthyroidism conferred the highest risk, especially for early AF. Treatment with thionamide was associated with late AF.