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Background: Atrioventricular block (AVB) is rare in hyperthyroidism (HTH). Little is known about the true prevalence, clinical course, optimal management, and outcomes of different types of AVBs in patients with HTH. To address these uncertainties, we aimed to conduct a systematic review by combining the available literature to provide more meaningful data regarding AVBs in HTH., Methods: We systematically searched PubMed, Scopus, Embase, and Google Scholar for articles reporting patients who developed AVB in the context of HTH. Data were analysed in STATA 16. The main outcomes included types of AVB, frequency of pacemaker insertion, and resolution of AVB. The systematic review is registered with the International Prospective Register of Systematic Reviews (PROSPERO) with the identification number CRD42022335598., Results: A total of 56 studies (39 case reports, 12 case series, 3 conference abstracts, 1 retrospective study, and 1 prospective observational study) with 87 patients were included in the analysis, with a mean age of 39.1 ± 17.6 years. Females constituted 65.7% ( n  = 48) of the cohort. Complete heart block (CHB) was the most commonly reported AVB ( N  = 45, 51.7%), followed by first-degree AVB (16.1%) and second-degree AVB (14.9%). Overall, 21 patients underwent pacing. A permanent pacemaker was inserted in one patient with second-degree AVB and six patients with CHB. Mortality was reported in one patient with CHB. The clinical course and management of HTH and AVBs did not differ in patients with CHB or lower-degree blocks. Apart from lower rates of goitre and more use of carbimazole in those who underwent pacing, no differences were found when compared to the patients managed without pacing., Conclusion: Current data suggest that CHB is the most common type of AVB in patients with HTH. Most patients can be managed with anti-thyroid management alone. Additionally, whether pacemaker insertion alters the clinical outcomes needs further exploration.

Liver dysfunction can occur in patients presenting with thyrotoxicosis, due to several different aetiologies. A 42-year-old man had mild liver dysfunction on presentation with hyperthyroidism due to Graves' disease (GD): ALT 65 (0-45 IU/L), fT4 41.2 (9-23 pmol/L), fT3 > 30.7 (2.4-6 pmol/L), and TSH < 0.01 (0.3-4.2 mIU/L). His liver dysfunction worsened following the initiation of the antithyroid drug (ATD) carbimazole (CBZ), with ALT reaching a zenith of 263 IU/L at 8 weeks following presentation. Consequently, CBZ was stopped, and he was managed with urgent radioiodine therapy. His liver function tests (LFTs) improved within 1 week of stopping carbimazole (ALT 74 IU/L). Thionamide-induced liver dysfunction is more typically associated with a 'cholestatic' pattern, although he had a 'hepatitic' pattern of liver dysfunction. The risk of liver dysfunction in GD increases with older age and higher titres of thyroid-stimulating hormone receptor antibody (TRAb). This review of the literature seeks to explore the possible causes of liver dysfunction in a patient presenting with hyperthyroidism, including thyrotoxicosis-induced liver dysfunction, ATD-related liver dysfunction, and the exacerbation of underlying unrelated liver disease.

One type of hypokalemic periodic paralysis that is associated with hyperthyroidism is called thyrotoxic periodic paralysis (TPP). TPP can be linked to any cause of hyperthyroidism, although Graves' disease is the most common cause. This sporadic variant of hypokalaemic periodic paralysis, thyrotoxic periodic paralysis, is characterized by rapid onset weakness in the proximal muscles. Due to their similar presentations, it is sometimes mistaken for familial periodic paralysis (FPP); however, biochemical tests and the presence of thyrotoxic characteristics can help distinguish the two conditions. Treatment options for this reversible illness include rapid potassium replacement and thyroid hormone normalization. To mitigate this potentially fatal complication, knowledge regarding the identification, prompt treatment, and avoidance of future episodes of TPP is crucial., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Thomas et al.)

Thyroid eye disease is a complex inflammatory disorder of the orbit that has gained tremendous interest over the past years, and numerous scientific efforts have been deployed to elucidate its pathophysiology for novel drug development. Our manuscript will delve into the molecular dysregulations involved in the pathogenesis of thyroid eye disease that led to its clinical manifestations. Abnormalities within the apoptotic pathway, inflammatory cascade, and autoimmune regulatory systems will be covered. We will further discuss the challenges involved in its diagnosis and management and provide a summary of the current diagnostic tools (i.e., molecular biomarkers, diagnostic scores) from the perspective of clinicians. Finally, our comprehensive literature review will provide a thorough summary of most recent preclinical and clinical studies around the topic of thyroid eye disease, with an emphasis on the manuscripts published within the last five years. We believe our manuscript will bring novelty within the field by bridging the fundamental sciences with the clinical aspect of this disease. This review will be a great tool for clinicians in better understanding the pathogenesis of thyroid eye disease while providing an outlook on future perspectives (i.e., liquid biopsies, artificial intelligence).

The current study was conducted to assess the relationship between the STAT3 gene variants rs744166 and rs2293152 and autoimmune thyroid disorder in the Pakhtun population of the province, of Khyber Pakhtunkhwa, Pakistan. Blood was collected from 100 healthy individuals and 400 thyroid-disordered patients. Of these, one hundred were diagnosed with Hashimoto's thyroiditis (HT), while 32 were confirmed as Grave's disease (GD) patients. T3, T4, and TSH serum levels were checked to diagnose thyroid disorders. The blood was analyzed for anti-thyroid peroxidase antibodies (Anti-TPOAb) (AESKULISA- ATPO - elisa kit), (Germany), and thyroid stimulating hormone receptor antibodies (TSHRAb), TSHR Ab elisa kit (Diametra Italy), respectively. PCR was used to amplify the targeted STAT3 gene polymorphisms from rs744166 (301 bp) and rs2293152 (365 bp) sequences and then digested by specific restriction endonucleases ( Alu I) and Aci I respectively. The disease displayed a female predominance. The genotype TC and CC of rs744166 showed a significant relationship with Grave's disease ( p = 0.002, OR = 0.28, 95 % CI = 0.11-0.77) in patients. The C allele contributed significantly to the disease in GD patients. The SNP rs2293152 significantly differed between GD patients and control ( p = 0.032, OR = 0.29, 95 % CI = 0.09-0.86). Similarly, the G and C alleles showed a significant ( p = 0.02) difference between GD patients and the control. No significant association was found for both SNPs in Hashimoto's thyroiditis disease. It is concluded that the STAT3 gene (rs744166 and rs2293152) was found to have a potential role in autoimmunity in GD patients. Still, it needs further studies with larger sample sizes in the Pakhtun population to understand this relationship., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

This article includes a review of information primary care physicians need to know direct their evaluation and treatment of thyroid disorders that include sick euthyroid, hyperthyroidism, hypothyroidism, and subclinical thyroid disorders., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mishra, Singh, Rajotiya, Debnath, Kumar, Singh, Snehpreet, Raj, Singh, Bareth, Nathiya and Singh Tomar.)

Background: Graves' disease (GD) and subacute thyroiditis (SAT) are important causes of thyrotoxicosis. The differentiation between these diseases is of great value because it will affect the management plan of either of them. The study aimed to assess the triiodothyronine/free thyroxine (T3/fT4) ratio as a criterion for the differentiation of hyperthyroidism due to GD and SAT., Method: A retrospective study with database retrieval was conducted at Faiha Specialized Diabetes, Endocrine and Metabolism Center (FDEMC), Basrah, southern Iraq. Patients attending the center who presented with thyrotoxicosis due to GD and SAT from January 2010 to January 2024 were included in the analysis that was conducted from October 2023 to February 2024. For comparison between GD and SAT, the baseline thyroid-stimulating hormone (TSH), fT4 and T3 were used to calculate the fT4 ratio (fT4 level (ng/dL)/1.7 ng/dL), T3 ratio (T3 level (ng/dL)/200 ng/dL), and T3/fT4 ratio (T3 level (ng/dL)/fT4 (ng/dL))., Results: As compared to SAT, patients with GD had a significantly lower TSH and higher T3, T3 ratio, and T3/fT4 ratio. A T3/fT4 ratio with a cutoff equal to or more than 25 had 95% sensitivity and 18.1% specificity for GD with 94.4% positive predictive value. Raising the cutoff to equal or more than 100 results in the reduction of sensitivity to 32.7% but with 100% specificity and positive predictive value., Conclusion: The T3/fT4 ratio presents as a valuable diagnostic tool in differentiating GD from SAT, with potential applications in refining the diagnostic approach to hyperthyroidism., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. The Ethical Committee of Faiha Specialized Diabetes, Endocrine and Metabolism Center (FDEMC) issued approval #11/10/23. The FDEMC Research Committee approved the study, from which ethical approval was obtained (reference #11/10/23) and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Alidrisi et al.)

With the progress of robotic transaxillary thyroid surgery (RTTS), the indications for this procedure have gradually expanded. This study presents the insights gained from performing 10,000 RTTS cases at a single institution, along with the expansion of indications over time. RTTS was performed on 10,000 patients using the da Vinci robot system between October 2007 and April 2023 at the Yonsei University Health System, Seoul, Korea. Among 10,000 patients, 9461 (94.0%) were diagnosed with thyroid cancer, whereas 539 (5.4%) had either a benign thyroid nodule or Graves' disease. Surgical procedures were performed using four-arm-based robots (da Vinci S, Si, or Xi) for 8408 cases (84.1%), with the remaining 1592 cases (15.9%) being performed using the da Vinci SP surgical robotic system. Notably, for 53 patients with nodules ≥ 5 cm, which were not included in the eligibility criteria of the previous study, RTTS was performed safely without significant complications. The most common postoperative complication was transient hypoparathyroidism (37.91%), and recurrence occurred in 100 patients with thyroid cancer (1.1%). In conclusion, RTTS appears safe and feasible from both surgical and oncological perspectives, and the spectrum of indications suitable for RTTS surgery is progressively expanding., (© 2024. The Author(s).)

Competing Interests: Conflict of interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: The diagnosis of Grave's disease (GD) poses a challenge. Thyrotropin-receptor antibodies (TRAb) are the key diagnostic feature of GD, as the American and European Thyroid Associations suggested., Aim of the Study: This study aims to find a cut-off level of TRAb in GD in Basrah., Methods: This is a retrospective study that included 617 patients with hyperthyroidism (530 GD and 87 non-Grave's disease (NGD) (thyroiditis or subclinical hyperthyroidism)). The candidates were patients presenting with hyperthyroidism who were referred for TRAb assay, while patients with thyroid carcinoma or nodular thyroid disease, pregnant ladies, and patients who were treated were excluded., Results: The manufacturer cut-off value of 1.75 IU/L had a sensitivity of 88.1%, specificity of 72.4%, positive predictive value (PPV) of 95.1%, and negative predictive value (NPV) of 50.0%. Our data analysis through receiver operating characteristic (ROC) statistics revealed that the optimum cut-off point with the highest total sensitivity and specificity was determined to be 3.95 IU/L, as it had a sensitivity of 76.9%, specificity of 98.8%, PPV of 99.7%, NPV of 41.3%., Conclusion: For a more accurate diagnosis of GD, the findings of the present study support the implementation of a higher TRAb cut-off value (3.95 IU/L) than that predefined by the manufacturer (1.75 IU/L)., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Radhi et al.)

Background: Thyroid dysfunction is the leading endocrine disorder worldwide. Iodine deficiency disorders, which were once the major etiology of thyroid dysfunctions, now have been succeeded by autoimmune thyroid diseases with the rise in aberrant salt ionization protocols. This study endeavors to access the level of thyroid autoantibodies viz. anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (TGA), and anti-thyroid stimulating hormone receptor (TRAb) in individuals with subnormal thyroid profiles., Methods: This hospital-based cross-sectional study was conducted at the Department of Clinical Biochemistry, Tribhuvan University for a period of six months. Using non-probability (purposive) sampling method, a total of 60 patients were enrolled with subnormal thyroid profiles to include the population who have not yet started medication. Thyroid hormones (free T3, free T4, TSH) and thyroid antibodies (anti-TPO, TGA, and TRAb) were measured. For non-parametric data, Chi-square test and Kruskal-Wallis test were used. Spearman's correlation was done to determine the association between variables., Results: Out of 60 participants, the majority of the population between 25 and 44 years were diagnosed with thyroid dysfunction with female preponderance. Among all, 40% (n = 24) had subclinical hyperthyroid states while, 60% (n = 36) had subclinical hypothyroid states, and 75% (n = 45) of the total exhibited positive thyroid antibodies. In subclinical hypothyroid patients with TSH above 10 µIU/ml, anti TPO (58.5%) and TGA (66.7%) positivity were highly prevalent. On the other hand, TRAb was exclusively positive in hyperthyroid condition (50% among the group) which is by far the first of its kind reported in Nepal., Conclusion: The rise in autoimmune thyroid disease among the Nepalese population infers that addressing iodine deficiency simply through salt iodinization may not be adequate to deal with the rising burden of thyroid disorders, especially in iodine-depleted areas. Also, the increasing prevalence of thyroid autoantibodies positivity in subclinical hypothyroidism in the Nepalese population accounts for the arduous screening and monitoring of autoimmune thyroid disorders in Nepal., (© 2023. BioMed Central Ltd., part of Springer Nature.)

This study aimed to examine the impact of hyperuricemia on various thyroid disorders with emphasized focus on differences resulting from different genders. 16094 adults aged ≥18 years were enrolled in this cross-sectional study using a randomized stratified sampling strategy. Clinical data including thyroid function and antibodies, uric acid, and anthropometric measurements were measured. Multivariable logistic regression was used to determine the association between hyperuricemia and thyroid disorders. Women who have hyperuricemia are at a significantly increased risk of developing hyperthyroidism. Women's risk of overt hyperthyroidism and Graves' disease may be markedly increased by hyperuricemia. Men with hyperuricemia did not differ significantly in their chance of acquiring any thyroid disorders.

Key Points: 10% of patients undergoing MAI decompression for TED developed new-onset diplopia MAI decompression remains an excellent option for orbital decompression for TED., (© 2023 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Thyroid eye disease (TED) can cause disfigurement and vision loss, most commonly in patients with Graves' disease. These symptoms are related to orbital inflammation subsequently cause proptosis and limited eye movement. Traditionally, TED is treated with corticosteroids to decrease inflammation and surgery once the disease stabilizes. However, multiple medications that play a role in immune modulation have been tested and found to be beneficial in treating TED, either as an adjuvant to steroids or in severe disease resistant to steroids. Teprotumumab-trbw, a novel monoclonal antibody sold under the trade name Tepezza ® , is the first immune modulator to be approved by the Unites States Food and Drug Administration (FDA) for TED. Teprotumumab-trbw targets the insulin-like growth factor-1 receptor, which is upregulated on orbital fibroblasts and decreases activation in patients with TED. The FDA approved this drug for patients with less than nine months of disease duration and high levels of disease activity. Multiple studies have shown significant positive results in disease modulation, as well as limited side effects., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Bocklud et al.)

Background: Insulin autoimmune syndrome (IAS) is a rare cause of hypoglycemia characterized by high levels of blood insulin autoantibodies. It has been documented that drugs containing sulfhydryl groups may result in IAS. In this study, we present two cases of IAS induced by methimazole, along with their corresponding treatments and a long-term follow-up after hospitalization., Case Presentation: We report two patients with Grave's disease (GD), carrying the HLA-DRB1 04:06 genotype, who experienced hypoglycemic episodes after taking methimazole. Inpatient treatments helped return their blood glucose levels to normal. Although no recurrences of hypoglycemia were present in the two cases studied, insulin autoantibodies remained positive for the previous follow-up sessions, which turned negative only three years after discharge., Conclusions: GD patients who carry the HLA-DRB1 04:06 genotype are prone to IAS if they take drugs containing sulfhydryl groups. It may take time for the elimination of insulin autoantibodies after the recovery from the hypoglycemic episode in IAS patients., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Purpose: To assess the evolution of proptosis asymmetry during the active phase of bilateral thyroid eye disease (TED)., Methods: A retrospective study was conducted on patients with bilateral, active TED. Patients were measured by a single observer, using Hertel exophthalmometry from the time of initial presentation, during the active phase of TED, to the stable phase, 24-months later. Asymmetric proptosis was defined as a >2 mm intra-orbital difference in Hertel measurements., Results: Fifty-one patients were enrolled. Patients presented at a mean time of 1.1 ± 2.9 months following the onset of TED symptoms. Stability of TED was established at 15.7 ± 12.3 months. At initial presentation, 41% of patients demonstrated asymmetric proptosis. Upon reaching the stable phase, asymmetric proptosis persisted in only 22% of patients. A decline in the rate asymmetric proptosis was greatest within the first 3 months of the active phase., Conclusions: Asymmetric proptosis is common in the setting of early active TED and decreases by 50% when the stable phase is reached. Therefore, diagnostic imaging is not routinely required to exclude alternative pathology in the cases of asymmetric TED. Perhaps more importantly, this finding supports the surgical paradigm of stable phase, graded orbital decompression, performed when the ultimate globe positions are achieved to avoid late postoperative asymmetry, resulting from the unanticipated evolution of proptosis when surgery is performed during the active phase of TED.

Background: There is overlap between movement disorders and neuroendocrine abnormalities., Objectives and Methods: To provide a systematic review on the association of thyroid dysfunction and movement disorders. Thyroid physiological function and classical thyroid disorders highlighting typical and atypical manifestations including movement disorders, as well as diagnostic procedures, and treatments are discussed., Results: Hypothyroidism may be associated with hypokinetic and hyperkinetic disorders. There is debate whether their concomitance reflects a causal link, is coincidence, or the result of one unmasking the other. Hypothyroidism-associated parkinsonism may resemble idiopathic Parkinson's disease. Hypothyroidism-associated hyperkinetic disorders mainly occur in the context of steroid-responsive encephalopathy with autoimmune thyroiditis, that is, Hashimoto disease, mostly manifesting with tremor, myoclonus, and ataxia present in 28-80%, 42-65% and 33-65% in larger series. Congenital hypothyroidism manifesting with movement disorders, mostly chorea and dystonia, due to Mendelian genetic disease are rare.Hyperthyroidism on the other hand mostly manifests with hyperkinetic movement disorders, typically tremor (present in three quarters of patients). Chorea (present in about 2% of hyperthyroid patients), dystonia, myoclonus, ataxia and paroxysmal movement disorders, as well as parkinsonism have also been reported, with correlation between movement intensity and thyroid hormone levels.On a group level, studies on the role of thyroid dysfunction as a risk factor for the development of PD remain non-conclusive., Conclusions: In view of the treatability of movement disorders associated with thyroid disease, accurate diagnosis is important. The pathophysiology remains poorly understood. More detailed case documentation and systematic studies, along with experimental studies are needed., (© 2023 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Aim: Although Graves' disease (GD) is common in endocrine practices worldwide, global differences in diagnosis and management remain. We sought to assess the current practices for GD in countries across Asia and the Pacific (APAC), and to compare these with previously published surveys from North America and Europe., Methods: A web-based survey on GD management was conducted on practicing clinicians. Responses from 542 clinicians were received and subsequently analysed and compared to outcomes from similar surveys from other regions., Results: A total of 542 respondents participated in the survey, 515 (95%) of whom completed all sections. Of these, 86% were medical specialists, 11% surgeons, and 3% nuclear medicine physicians. In addition to serum thyroid-stimulating hormone (TSH) and free thyroxine assays, most respondents would request TSH-receptor autoantibody (TRAb) measurement (68%) during initial work-up. Thyroid ultrasound is requested by about half of respondents (53%), while the use of nuclear medicine scans is limited. The preferred first-line treatment is anti-thyroid drug (ATD) therapy (79%) with methimazole (MMI) or carbimazole (CBZ), followed by radioiodine (RAI; 19%) and surgery (2%). In case of surgery, one-third of respondents would opt for a subtotal rather than a total thyroidectomy. In case of mild Graves orbitopathy (GO), ATDs (67%) remains the preferred treatment, but a larger proportion of clinicians prefer surgery (20%). For a patient with intention to conceive, the preferred treatment pattern remained unchanged, although propylthiouracil (PTU) became the preferred ATD-agent during the first trimester. In comparison to European and American practices, marked differences were noted in the relatively infrequent usage of nuclear medicine scans and the overall higher use of a ATDs and β-blockers and adjunctive ATD-treatment during RAI in the APAC-group., Conclusion: Although regional differences regarding the diagnosis and management of GD are apparent in this first pan-Asia-Pacific survey, this study reveals the overall approach to the management of this disease in Asia-Pacific generally tends to fall between the trends appreciated in the American and European cohorts., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Thyroid eye disease (TED), an autoimmune inflammatory disorder of the orbit, presents with a potential array of clinical sequelae. The pathophysiology behind TED has been partially characterized in the literature. There remain certain elusive mechanisms welcoming of research advances. Disease presentation can vary, but those that follow a characteristic course start mild and increase in severity before plateauing into an inactive phase. Diagnosis and evaluation include careful physical examination, targeted laboratory work up, appropriate imaging studies, and tailored treatment regimens. Special consideration may apply to certain populations, such as pediatric and pregnant patients.

Background: Interferon in combination with ribavirin has been the standard of care for chronic hepatitis C virus infection (HCV) for the past few decades. However, its effect on the risk of autoimmune diseases (ADs) among patients with HCV infection remains unclear. We assessed the potential association between interferon-based therapy (IBT) and AD risk in patients with HCV infection., Methods: This retrospective cohort study identified patients diagnosed with HCV infection between January 1, 2006, and December 31, 2015, from Taiwan's National Health Insurance Research Database. In total, 16,029 patients with HCV infection who received IBT and 141,214 patients with HCV infection who did not receive IBT were included. Both cohorts were followed up to assess the development of ADs. Hazard ratios (HRs) were calculated using the Cox proportional hazards regression model, which was adjusted for potential confounders., Results: The median follow-up period for IBT and non-IBT users was 4.53 and 3.34 years, respectively. No significant difference in the risk of overall ADs (adjusted HR [aHR]: 0.96, 95% confidence interval [CI]: 0.81-1.14) or systemic ADs (aHR: 0.88, 95% CI: 0.71-1.10) was noted during the study period. However, a slight increase in the risk of organ-specific ADs was noted among IBT users (incidence rate ratio: 1.33, 95% CI: 1.02-1.72). Furthermore, analysis of AD subgroups revealed a significant increase in the risks of Graves' disease (aHR: 6.06, 95% CI: 1.27-28.8) and Hashimoto's thyroiditis (aHR 1.49, 95% CI 1.01-2.21) among IBT users., Conclusions: IBT use increases the risk of autoimmune thyroid diseases (Hashimoto's thyroiditis and Graves' disease) in patients with HCV infection to a greater extent than non-IBT use., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chou, Yeh, Lin, Chang, Hsu, Shen, Kuo, Chen, Chen and Chang.)

Objective: To evaluate the prevalence and clinical significance of nonuniform technetium ( 99m Tc) uptake among patients with Graves' disease (GD)., Design, Patients and Measurements: Patients with GD, referred between July 2005 and March 2018, had Tc 99 - uptake scans and TSH-receptor antibody (TRAb) measured before antithyroid drug (ATD) therapy. Risk of relapse after ATD cessation was monitored until June 2021 and compared between GD patients based on uptake patterns., Results: Of the 276 GD patients (mean age, 49.8 years; 84% female), 25 (9.0%) had nonuniform Tc 99 uptake. At diagnosis, individuals with nonuniform uptake were older (mean age of 61.8 vs. 48.5 years, p < .001), had lower mean thyroid hormone levels (free thyroxine: 36.3 vs. 45.4  pmol/L, p = .04 and free triiodothyronine: 10.0 vs. 17.8 pmol/L, p < .001) and median TRAb levels (4.2 vs. 6.6 U/L, p = .04) compared with those with a uniform uptake. Older age was a significant predictor for the presence of nonuniform uptake in GD patients; odds ratio (95% confidence intervals) of 1.07 (1.03 - 1.10). The risk of relapse was similar in both groups after a median (IQR) follow-up of 41 (13-74) months after ATD cessation (56.0% vs. 46.3%, respectively); hazard ratio (95% confidence intervals) of 1.74 (0.96-3.15)., Conclusions: Nonuniform radio-isotope uptake is seen in 1 in 11 patients with GD which could be misdiagnosed as toxic multinodular goitre if TRAb levels are not measured. Treatment of GD patients with nonuniform radio-isotope uptake with ATD therapy as first-line appears to be equally effective as compared with those with uniform uptake. TRAb testing should be the main diagnostic test for patients with suspected GD with radio-labelled uptake scans being reserved for those who are TRAb negative., (© 2022 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

Background and Objectives : Vitamin D deficiency is involved in numerous pathologies, including endocrine pathology. The purpose of this review consists of presenting the role of vitamin D in the pathophysiology of certain endocrine disorders, autoimmune thyroid disorders (Hashimoto's disease and Grave's disease), diabetes mellitus, and obesity, and whether its supplementation can influence the outcome of these diseases. Materials and Methods : Review articles and original articles from the literature were consulted that corresponded with the thematic. Results : Vitamin D deficiency is frequently encountered in endocrine disorders and supplementation restores the normal values. In Hashimoto's disease, vitamin D deficiency appears to be correlated with a higher titer of anti-TPO antibodies and with thyroid volume, and supplementation was associated with reduction of antibodies in some studies. In other studies, supplementation appeared to reduce TSH levels. In Grave's disease, there was a significant correlation regarding vitamin D levels and thyroid volume respective to the degree of exophthalmos. In diabetes mellitus type 2 patients, supplementation led to some improvement of the HOMA-IR index and HbA1c, whereas obesity data from literature do not report significant beneficial findings. Conclusions : Vitamin D deficiency is highly prevalent in endocrine disorders and its supplementation appears to have numerous beneficial effects.

Thyroid eye disease (TED) is an autoimmune disorder that is associated with thyroid gland dysfunction which causes muscle and orbital fat enlargement. This case report is aimed to present a case of sight-threatening TED and how we should manage this condition. We present a case of patient with chief complaint of vision loss and prominent eyes for 5 months prior to the visit to our eye hospital. Patient had sought advice from an ophthalmologist and internist. TED was eventually diagnosed 2 months after consulted with an ophthalmologist in the rural area. According to EUGOGO guidelines, TED with sight-threatening condition should be treated with glucocorticoid IV 500-1000 mg for 3 days consecutively. Although the patient was already given steroid injection for the initial treatment, the dosage was inadequate. After the inflammation process was reduced, the patient was reluctant to have an orbital decompression that was suggested. Hence, TED progressed continuously besides sight-threatening complications arising. He indeed underwent fat decompression and tarsorrhaphy as eyelid surgery to prevent corneal exposure. In follow-up, both visual acuity and corneal improvement were finally achieved. In the management of TED, collaboration between ophthalmologist and internist, who may be specialized in endocrinology, is imperative. They should be able to manage TED promptly and correctly, hence sight-threatening and other complications can be prevented and satisfactory results are achieved. Fat decompression should be considered as a good help to improve visual acuity nevertheless orbital decompression cannot be done.

Purpose: Current literature suggests 12-18 months of antithyroid drug (ATD) treatment for patients with Graves' disease, but the risk of relapse is high. Although some studies reported better outcomes of long-term ATD treatment, recent data that suggest the optimal treatment duration are limited., Methods: We performed a multicenter retrospective cohort study of 908 patients newly diagnosed with Graves' disease between 2006 and 2013. The relapse rate according to ATD treatment duration was analyzed., Results: After initial ATD treatment, 338 patients (37.2%) had relapsed. The relapse rate according to ATD treatment duration was 42.4% at 1 year, 38.5% at 2 years, 33.8% at 3 years, 31.7% at 4 years, 30.2% at 5 years, 27.8% at 6 years, and 19.1% at more than 6 years, respectively, demonstrating a significant decreasing trend (p = 0.003). In a multivariable Cox regression analysis, ATD treatment duration was an independent risk factor for relapse (p = 0.043)., Conclusions: The longer that ATD therapy is used, the lower the relapse rate is in patients with Graves' disease. Long-term ATD treatment may be considered in Graves' patients who do not show complications or an economic burden from hyperthyroidism., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: The purpose is to understand the natural history and physical findings in thyroid eye disease (TED) patients with severe dry eye symptoms (DES)., Methods: Prospective cohort study, studying DES in TED patients over two years. Baseline data included clinical activity score (CAS), time since disease onset, punctate epithelial erosions (PEE), lagophthalmos, superior limbic keratoconjunctivitis (SLK), and marginal reflex distance 1 (MRD1). Ocular Surface Disease Index (OSDI) was utilized to measure symptomatology and scores > 33 (severe) were the primary outcome measure. Multivariate logistic regression was performed on two groups (<9 months, >9 months) to assess if variables change in early versus late disease., Results: 88 met the inclusion criteria. 80.7% (n = 71) were female. There were 42 patients in the group with onset of symptoms under nine months and 46 patients over nine months. Mean CAS score was greater under nine months (2.45) than over nine months (1.29) ( p < .05).In the multivariate logistic regression for the group presenting with symptoms under nine months, CAS was the only significant predictor of severe OSDI. Every increase in CAS of one yielded a 2.0x increased risk of severe OSDI. For the patients over nine months from onset, PEE was the significant predictor of severe OSDI. PEE was associated with a 5.9x increased risk of severe OSDI., Conclusions: Severe DES correlate with inflammatory features within the first nine months. Afterward, presence of PEE became more important. DES in TED tends to be a manifestation of orbital inflammation early in disease and exposure later.

Autologous hematopoietic stem cell transplantation (aHSCT) represents an effective treatment for systemic sclerosis (SSc), but it also can cause immunological adverse events (iAEs). Therefore, we aimed to determine the frequency of iAEs [engraftment syndrome (ES) and secondary autoimmune disorder (sAD)] and to identify potential risk factors for their development in a retrospective analysis on 22 patients similarly transplanted due to SSc. While nine patients (41%) suffered from ESs, seven sADs occurred in six patients (27%). Patients who developed ES were older in our cohort (52.45 vs. 42.58 years, p = .0433, Cohen's d = 0.86), and cardiac involvement by SSc was associated with development of ES (OR = 40.11, p = .0017). Patients with manifestation of sAD had a higher modified Rodnan skin score (mRSS) reduction after aHSCT (90.50% vs. 60.00%, p = .0064, r = .65). Thus, IAEs are common after aHSCT for SSc and can occur in different stages during and after aHSCT with characteristic clinical manifestations. Good cutaneous response after aHSCT might be considered as a risk factor for sAD, and higher age at aHSCT and cardiac involvement might be considered as risk factors for the development of ES., Competing Interests: P-PS received travel grants from Janssen-Cilag and AbbVie. MF reported travel grants from AbbVie, Novartis, Janssen, and Eli Lilly and compensation for board memberships from AbbVie. MG received travel grants from AbbVie, Chugai, Eli Lilly, Hexal, Janssen-Cilag, Novartis, and Pfizer. Janssen, Eli Lilly, Chugai, Roche, Takeda (Shire), AbbVie, and Novartis supported ES. H-PT received speaker’s fees, travel grants, research funding, or compensation for consultancies or board memberships from AbbVie, BMS, Chugai/Roche, Eli Lilly, Gilead, Janssen, Novartis, Sandoz/Hexal, Sanofi Aventis, and Takeda (Shire). JH reported speaker’s fees, travel grants, and research funding from AbbVie, BMS, Boehringer/Ingelheim, Celgene, Chugai/Roche, Eli Lilly, Janssen-Cilag, Novartis, SOBI, Pfizer, and UCB. MS received speaker’s fees, travel grants, research funding, or compensation for consultancies or board memberships from AbbVie, Actelion, AstraZeneca, BMS, Boehringer/Ingelheim, Celgene, Chugai/Roche, Eli Lilly, Genzyme, Gilead, Hexal/Sandoz, Janssen-Cilag, MSD, Novartis, Pfizer, Sanofi Pasteur, Takeda (Shire), and UCB (less than $10,000 each). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Strunz, Froehlich, Gernert, Schwaneck, Fleischer, Pecher, Tony, Henes and Schmalzing.)

Celiac disease (CD) and autoimmune thyroid diseases (AITD) like Hashimoto's thyroiditis (HT) and Graves' disease (GD) frequently coexist, entailing numerous potential impacts on diagnostic and therapeutic approaches. Possible correlations might exist through gut microbiota, regulating the immune system and inflammatory responses, promoting autoimmune diseases, as well as shared cytokines in pathogenesis pathways, cross-reacting antibodies or malabsorption of micronutrients that are essential for the thyroid like iron or vitamin D. Vitamin D deficiency is a common finding in patients with AITD, but might protect from autoimmunity by wielding immunoregulatory and tolerogenic impacts. Additionally, vitamin D is assumed to be involved in the onset and progression of CD, presumably plays a substantial protective role for intestinal mucosa and affects the thyroid via its immunomodulatory effects. Iron is an essential micronutrient for the thyroid gland needed for effective iodine utilization by the iron-dependent enzyme thyroid iodine peroxidase (TPO). Despite being crucial for thyroid hormone synthesis, iron deficiency (ID) is a common finding in patients with hypothyroidism like HT and is frequently found in patients with CD. A literature research was conducted to examine the interplay between CD, AITD, vitamin D and iron deficiency. This narrative review highlights the relevant correlation of the two disease entities CD and AITD, their reciprocal impact and possible therapeutic options that should be further explored by future studies.

Study Question: Is thyroid autoimmunity associated with a higher risk of low ovarian reserve and POI?, Summary Answer: Thyroid autoimmunity significantly increases the risk of POI in women., What Is Known Already: POI is closely related with autoimmune disease, and according to some studies, thyroid autoimmunity (TAI) may account for diminished ovarian reserve. However, no large-scale cohort study has demonstrated the association between TAI and POI., Study Design, Size, Duration: A longitudinal population-based retrospective cohort study on the National Health Insurance Research Database (NHIRD) was designed. Since 1 March 1995, the National Health Insurance (NHI) programme in Taiwan has included 99.9% of the 23 million population of Taiwan. Patients between 1 January 2000 and 31 December 2012 were eligible for recruitment, and 21 325 subjects were analysed in our study., Participants/materials, Setting, Methods: Two cohorts, Hashimoto's and Grave's disease, were composed of patients with autoimmune thyroid disease between 20 and 40 years of age. The comparison cohorts consisted of patients in the NHIRD without autoimmune thyroid disease matched by age at a ratio of 1:4 in subject numbers., Main Results and the Role of Chance: The Hashimoto's disease (HD) cohort, Grave's disease (GD) cohort and two comparison cohorts were followed up until a diagnosis of amenorrhoea, menopausal syndrome, other ovarian failure or infertility due to ovarian failure had been made. Compared statistically with the non-HD cohort, patients with HD exhibited an 89% higher risk of amenorrhoea (95% CI =1.36-2.61). The HD patients exhibited a 2.40-fold higher risk of infertility due to ovarian failure than the non-HD subjects (hazard ratio (HR)=2.40, 95% confidence interval (CI)=1.02-5.68). In comparison with the non-GD cohort, patients with GD exhibited a 68% higher risk of amenorrhoea (95% CI = 1.43-1.98) after adjustment. According to the Kaplan-Meier analysis, the cumulative incidence of amenorrhoea and menopausal syndrome was significantly higher in the TAI groups than in the control groups., Limitations, Reasons for Caution: This is a retrospective study using ICD-9 disease code analysis to determine the statistical association between two diseases., Wider Implications of the Findings: Given that autoimmune thyroid disease is highly associated with early diminished ovarian reserve or even premature ovarian failure or POI, the options for infertility treatment may be re-directed to more efficient methods in infertile patients diagnosed with the disease. If the ovarian reserve is normal at the time of diagnosis of thyroid autoimmune disease, close follow-up of ovarian reserve may be highly recommended., Study Funding/competing Interest(s): This study is supported in part by Taiwan Ministry of Health and Welfare Clinical Trial Center, Grant Number: MOHW109-TDU-B-212-114004. The authors have no conflicts of interest to declare., Trial Registration Number: N/A., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)