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Background: Several meta-analyses have found no association between Graves' disease (GD) and an increased risk of incident diabetes; however, the intricate relationship between thyroid dysfunction and diabetes remains underexplored. In this study, we aimed to evaluate the risk of incident type 2 diabetes (T2DM) in a population newly diagnosed with GD, focusing on different treatment methods and treatment duration. Methods: This was a retrospective population-based study utilizing data from the Korean National Health Insurance database. We included 36,243 patients with GD and 36,243 controls, matched with age and sex. We calculated the incidence of T2DM among patients and controls based on treatment methods, such as medical therapy, radioactive iodine therapy (RAIT), and surgery. We examined the cumulative dose and duration of antithyroid drug (ATD) use for each patient. Results: The majority of patients (34,867, 96.2%) were treated with ATDs, followed by RAIT (1093 patients, 3%), and surgery (283 patients, 0.8%). After adjusting for age; sex; income; comorbidities, including hypertension, dyslipidemia, and cancer; body mass index; smoking; drinking; and exercise, patients with GD exhibited a higher risk of developing diabetes (hazard ratio [HR] = 1.13 [95% confidence interval 1.06–1.21]) than controls (5.1% vs. 4.5%, respectively). While the risk was the highest within the first six months after GD diagnosis (HR = 3.21), it was significant between six months and two years (HR = 1.36) and was comparable with the controls two years after GD diagnosis (HR = 0.93). A longer duration of ATD treatment and a higher cumulative dose were associated with an increased risk of diabetes. However, the risks for T2DM did not differ according to treatment modality or clinical outcomes, which was probably related to the small number of patients in each subgroup. Conclusions: Our findings highlight the negative impact of GD on the development of T2DM. Patients newly diagnosed with GD can be considered for diabetes screening to facilitate early detection and intervention. [ABSTRACT FROM AUTHOR]

Purpose: Hyperthyroidism guidelines have not been updated over the past five years, despite numerous data on the subject, and recent studies providing a wide variation in treatment success rates. We aim to compare the effectiveness and safety of treatment modalities in patients with Graves' disease or toxic nodular disease. Methods: Single center retrospective cohort study of Graves' disease and toxic nodular disease patients treated between 1983 and 2023. Results: A total of 411 patients were treated for hyperthyroidism, 245 due to Graves' disease and 166 due to or toxic nodular disease, followed for a median of 7 years. In Graves' disease, 90.2% were treated with antithyroid drugs over 250 cycles, achieving 41.7% cumulative remission. Half of all relapses (50.9%) occurred in the first year, 76.3% in the first three years, and 98.3% within nine years. Treatment periods of 12–24 months showed higher remission and lower relapse rates than longer periods. I-131 was used in 103 cycles with 82.5% remission and 7.1% relapse. A total of 29 thyroidectomies resulted in 100% remission, with no relapse. In toxic nodular disease, surgery was the most frequently used treatment (54.5%), followed by I-131 (37.1%). Conclusion: Our findings support antithyroid drugs as the preferential first-line treatment for Graves' disease, allowing for euthyroidism with minimal adverse effects. Given the propensity for relapse, we suggest a rigorous monitoring, particularly within the first three years. In toxic nodular disease, surgery should be the preferred option, with I-131 being reserved for single adenomas and small goiters. [ABSTRACT FROM AUTHOR]

Background: Autoimmune thyroid diseases (AITD) and allergic rhinitis (AR) are prevalent conditions; however, limited research has investigated their association. This study aimed to evaluate whether AR can be considered a risk factor for developing AITD. Methods: A retrospective cohort study analyzed the records of AITD patients who visited Alexandria University Students Hospital between January 2017 and December 2021. The parameters included in the study were thyroid-stimulating hormone (TSH), Free triiodothyronine (FT3), free thyroxine (FT4), thyroid peroxidase antibodies (TPOAb), thyrotropin receptor antibody (TRAb), eosinophils count, and IgE. Results: Out of 4,515 eligible patients, 41.7% were diagnosed with AR in addition to AITD. Among the patients with both conditions, 81% were females, their mean age was 45.71 ± 24.14 years, and the mean duration of AITD was 7.32 ± 2.11 years. The Kaplan–Meier analysis revealed that the AR cohort had a higher cumulative incidence of AITD than did the non-AR cohort (log-rank test, p = 0.001). Multivariate-adjusted hazardous ratios showed that patients with AR, female sex, higher white blood cell count, and diagnosis in November had a higher risk of developing AITD. Conclusions: Screening for AITD should be conducted at the time of diagnosis of AR as it could be a risk factor for AITD. [ABSTRACT FROM AUTHOR]

In China, due to the risks of hypothyroidism after radioiodine treatment, radioiodine is not commonly used as a first-line treatment. In this study, factors influencing the development of hypothyroidism after 131I therapy for Graves' hyperthyroidism were evaluated. This was a retrospective study with a 12-month follow-up. Retrospectively, we investigated 1,264 patients with diagnosed Graves' disease who received 131I therapy using the Marinelli-Quimby formula. The first three months after 131I therapy, hypothyroidism risk was higher among patients with lighter thyroid weight, higher levels of thyroglobulin antibody (TGAb), and shorter durations of Antithyroid drug (ATD) treatment before 131I therapy (P < 0.05). After 6 months, patients with lighter thyroid weight, shorter ATD treatment duration before 131I therapy, and higher iodine intake showed an increased risk of hypothyroidism. (P < 0.05). After one year, lower 24-h iodine uptake was the only risk factor for hypothyroidism (P < 0.05). Our results show that 131I is an effective therapy for GD. Even if over time, the occurrence of hypothyroidism may ultimately depend on the patients' radiosensitivity to 131I before treatment. But in the first 3 to 6 months or even one year, we can still take measures to effectively improve the quality of life of patients. [ABSTRACT FROM AUTHOR]

Up to 80% of children/adolescents with Graves' disease (GD) may require second-line treatment with either surgery or radioactive iodine (RAI) therapy after treatment with antithyroid drugs. These interventions aim to induce permanent hypothyroidism, but are not always successful. We aimed to evaluate the initial success rate (within the first year) of RAI treatment and its determining factors as second-line treatment in teenagers with GD. We also assessed the tolerability of RAI therapy and the onset speed of RAI-induced hypothyroidism. We conducted a retrospective chart review of children < 18 years treated with RAI (scaled fixed dose) for GD between January 2007 and December 2022 at the UZ Brussels. Fourteen teenagers treated with RAI were identified. Their ages at time of treatment ranged from 9.8 to 17.3 years, with administered I131 doses between 5.8 and 15.0mCi (median 7.9mCi). All but two patients responded within six months. Thyroxine treatment was started between 4 and 14 weeks (median 9 weeks) after RAI therapy. The time to thyroxine substitution correlated positively with age (Rho = 0.498; p = 0.099) and total I131-dose (Rho = 0.582; p = 0.047). One patient experienced transient RAI induced sialadenitis. None of the patients relapsed during a follow-up period of 1.2 to 13 years. A cure rate of 86% was observed in GD teenagers receiving a second-line RAI treatment, with no major complications. Most patients became hypothyroid within three months, underscoring the importance of early thyroid function monitoring. [ABSTRACT FROM AUTHOR]

Objective: To investigate serum TL1A levels and their correlation with Th17 cells, IL-17, and IL-21 in children with Graves' disease (GD). Methods: Thirty-seven children (12 males and 25 females) aged 9-14 years with newly diagnosed and untreated GD were enrolled in this study. Serum TL1A, IL-17, and IL-21 levels were measured using enzyme-linked immunosorbent assay (ELISA). The percentage of Th17 cells in peripheral blood was determined by flow cytometry. The correlation between serum TL1A levels and Th17 cells, IL-17, and IL-21 was analyzed using Pearson's correlation coefficient. Results: Serum TL1A levels and the percentage of Th17 cells were significantly higher in children with GD compared to healthy controls (P<0.05). Serum IL-17 and IL-21 levels were also significantly elevated in GD patients (P<0.05). Serum TL1A levels positively correlated with the percentage of Th17 cells (r=0.625, P<0.05), IL-17 (r=0.573, P<0.05), and IL-21 (r=0.542, P<0.05) in children with GD. Conclusion: Serum TL1A levels are increased in children with GD and positively correlate with Th17 cells, IL-17, and IL-21, suggesting that TL1A may play a role in the pathogenesis of GD by regulating Th17 cell differentiation and the production of IL-17 and IL-21. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the utility of apparent diffusion coefficient (ADC) values of extraocular muscles (EOMs) in differentiating activity of thyroid eye disease (TED). Method: Forty-two TED patients who underwent diffusion tensor imaging(DTI) were retrospectively enrolled in this study, including 29 patients in analysis group and 13 patients in validation group. The mean, maximum and minimum ADC value of each EOM were regarded as ADCmean, ADCmax and ADCmin. The difference between ADCmax and ADCmin was regarded as △ADC. The correlations between ADCmean or △ADC of each EOM and clinical activity score (CAS) were assessed. Results: In analysis group, ADCmean differed between active and inactive eyes and positively correlated with CAS in IR (P < 0.05), not in SR,LR and MR(all p > 0.05). While △ADC differed between two groups and negatively correlated with CAS in all EOMs (all P < 0.05). ADCmean predicted active disease at cut-off value of 1259.3 × 10−6mm2s−1 with sensitivity of 66.7% and specificity of 71.4% in IR[area under curve = 0.667, P < 0.05]. △ADC predicted disease activity in all EOMs [area under curve 0.658–0.746,all P < 0.05]. The cut-off values of △ADC were 382, 823,520 and 572 × 10−6mm2s−1 with sensitivity of 80.0%, 50.0%, 43.3%, 83.3% and specificity of 67.9%, 85.7%, 89.3%, 60.7% in SR, IR, MR, and LR respectively. There were no significant differences in the predictive efficacy among all cut-off values. Conclusions: Our results showed that DTI is a valuable tool in the assessment of disease activity of TED. Both ADCmean of IR and △ADC of all four EOMs can be used in discriminating disease activity with the same predictive power. [ABSTRACT FROM AUTHOR]

Graves' disease (GD) is an autoimmune disorder characterized by activation of the TSH receptor by stimulatory autoantibodies (TSH Receptor Antibodies, or TRAbs), leading to unregulated thyroid hormone production. Diagnosis is largely based on the typical clinical picture and laboratory thyroid panel. Establishment of elevated serum levels of TRAbs by competitive binding assay or cell-binding assay has its unique role in diagnosis and management of GD, especially in the differential diagnosis, therapy selection, prognostication, evaluation of thyroid function during pregnancy, peri-conceptional and neonatal thyroid workup, and in certain special situation. Inclusion of TRAbs in GD diagnostic algorithm can improve cost-effectiveness of GD management. The current best practice guidelines were developed to provide evidence-based recommendations in the use of TRABs in GD management for healthcare providers in South Asia. A panel of endocrinologists with minimum 10 years of clinical experience in thyroid disorders reviewed existing literature and their quality, and after deliberation and discussion, developed 21 recommendations surrounding the best practices surrounding the role of TRAbs in GD management. [ABSTRACT FROM AUTHOR]

Introduction: Graves' Orbitopathy (GO) is an autoimmune disorder characterized by inflammation of orbital tissues, leading to various ocular manifestations, including ocular surface disease. This cross-sectional study aimed to assess the presence of ocular surface disease using the Ocular Surface Disease Index (OSDI) in patients with Graves' disease (GD) and moderate-to-severe active GO compared to those with GD and mild non-active GO. Additionally, we aimed to investigate the correlation between ocular surface disease and the eye features of GO. Methods: Consecutive GD patients with GO referred to the Ophthalmology and Endocrinology Units of the University Hospital of Pisa between June 2022 and February 2023 were enrolled. OSDI scores were obtained from 79 GD patients, categorized into moderate-to-severe active GO and mild non-active GO groups. Results: OSDI scores were significantly higher in patients with moderate-to-severe active GO compared to those with mild non-active GO (P=0.0006). A cutoff value of 33 for positive tests revealed a higher frequency of pathological OSDI in moderate-to-severe active GO patients compared to mild non-active GO patients (P=0.0221; OR 3.673, CI 1.277-9.531). Within the moderate-to-severe active GO group, a significant positive correlation was found between OSDI and Clinical Activity Score (CAS) (R= 0.3867, 95% CI from 0.1403 to 0.5880; P=0.0030). Using a cutoff value of 55 (the 75th percentile of the study population), patients with CAS ≥ 3 had a significantly higher proportion of pathological OSDI compared to those with CAS <3 (P=0.0039; OR 4.075, CI 1.619-10.39). Proptosis values ≥ 22 mm and the presence of lagophthalmos were identified as significant risk factors for ocular surface disease development (P=0.0406 and P=0.0493, respectively). Discussion: Our study highlights a significantly higher prevalence of ocular surface disease, as measured by OSDI, in patients with moderate-to-severe active GO compared to those with mild non-active disease. The degree of GO activity positively correlates with ocular surface involvement, and proptosis and lagophthalmos increase the risk of its occurrence. These findings emphasise the importance of assessing and managing ocular surface health in GO patients. Early identification and appropriate treatment of ocular surface disease need to be pursued to improve patient management. [ABSTRACT FROM AUTHOR]

Introduction: Reports in adults indicate that Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2) infection and vaccination trigger the expression of autoimmune disease such as Graves' disease, but the incidence of new onset Graves' disease and its temporal relationship to the peaks of COVID-19 cases in children are unclear. Methods: This is a retrospective study of children and adolescents with new-onset Graves' disease diagnosed between September 2017 and August 2022, N=156, mean age of 12.5 ± 4 year (y), with a range of 2.9-17.9y. There were 119 female (76.3%) and 37 male (23.7%) subjects. Subjects were categorized into 2 groups: pre-COVID-19 era Graves' disease (n=63, age 12.5 ± 3.3y), and COVID-19 era Graves' disease (n=93, age 12.4 ± 4.4y). We calculated incidence rate based on new cases of Graves' disease and total number of new patient referrals to our endocrine clinic. We first compared the demographic, clinical and biochemical data between the above 2 groups; and also, between subjects with either a history of COVID-19 infection (n=23) or vaccination (n=17) to a control group (n=63). Results: The incidence of Graves' disease was significantly higher during the pandemic: pre-COVID-19 versus the COVID-19 era, n=55, 0.56% vs n=93, 0.9%, p=0.005, after accounting for the total number of annual new patient referrals during the study period. The rise in the cases of Graves' disease followed the spikes in the number of cases of COVID-19 in NY. There was also a statistically significant difference in the race distribution between the pre-COVID-19 and the COVID-19 era (p=0.026). Discussion: The incidence of Graves' disease increased significantly in children living in New York during the COVID-19 pandemic. The temporal relationship between the peaks of COVID-19 cases and the increased cases of new onset Graves' disease suggest possible autoimmune triggering by SARS-CoV-2. [ABSTRACT FROM AUTHOR]

We report a case of a 60‐year‐old lady with metastatic follicular thyroid carcinoma (FTC) who was presented with thyrotoxicosis and heart failure symptoms after total thyroidectomy. Clinical features and investigations led to the diagnosis of functional metastatic FTC with concomitant thyrotoxicosis. Levothyroxine therapy was stopped, and she was treated with propylthiouracil (PTU) followed by serial radioiodine treatments (RAITs) with good control of thyrotoxicosis and metastases. Despite having a very high disease burden with metastatic FTC, she has been able to maintain her functional status thus far, 4.5 years after initial diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: TSH-receptor antibodies (TRAb) directed against the TSH receptor (TSH-R) induce hyperthyroidism in patients with Graves′ disease (GD). TRAb detected by previous radioimmunoassay only reflects the presence of autoantibodies, but not the function of such antibodies. Thyroid stimulating immunoglobulins (TSI) is a relatively new method for assessing TSH-receptor antibodies function. The aim of this study was to investigate the role of TSI in the diagnosis and management of GD. Methods: Patients with newly diagnosed GD (n=140, age 38.00 ± 11.99 years, 106 women) received pharmacological therapy (methimazole) up to 18 months in the outpatient or inpatient department of the Second People's Hospital of Foshan City from January 2013 to December 2018. GD was identified by clinical signs and symptoms and relevant laboratory tests. Blood samples for TSI and TRAb and other thyroidal biomarkers were obtained at baseline and at three times during the follow-up. All patients with GD were followed up for at least 5 years to see if the patient was cured or had relapsed. Results: TSI and TRAb in GD patients were significantly higher than those in the normal control group (P <0.001), and there was a strong correlation between TSI and TRAb in GD patients (P <0.001). After treatment, TSI and TRAb significantly decreased (P <0.05), TSI and TRAb in patients with disease course more than 2 years were significantly higher than those in patients with disease course less than 2 years (P <0.05), There was no statistically significant difference in TSI and TRAb at initial diagnosis between patients with a disease duration of more than 2 years and less than 5 years and those with a disease duration of more than 5 years (P >0.05); if the patients were still positive for TSI or TRAb antibodies at 5 years of follow-up after treatment with anti-hyperthyroidism medication, the patients were at a higher risk of relapse (P <0.001). Conclusion: The higher TSI at the initial diagnosis of GD, the longer duration of treatment with anti-hyperthyroid drugs and the higher risk of relapse. Compared with TRAb, serum TSI level is also important in the clinical diagnosis and prognosis of GD, but which one is superior to the other needs further study. [ABSTRACT FROM AUTHOR]

Background: Although observational studies have suggested a correlation between Sjogren's syndrome (SS) and autoimmune thyroid disease (AITD), a conclusive evidence supporting a causal relationship is still lacking. This study aims to explore the potential causal relationship between SS and AITD. Methods: Using genome‐wide association studies, we performed a bidirectional two‐sample Mendelian randomization (MR) analysis. In our analysis, the random‐effects inverse variance weighted (IVW) method was predominantly employed, followed by several sensitivity analyses, which include heterogeneity, horizontal pleiotropy, outliers, and "leave‐one‐out" analyses. Results: In the study of the effect of SS on AITD, SS was associated with an increased risk of Hashimoto's thyroiditis (OR = 1.09, 95%CI 1.02–1.16, p = 0.01). The causal associations were supported by sensitivity analyses. In reverse MR analyses, Hashimoto's thyroiditis (OR = 1.24, 95% CI 1.08–1.42, p < 0.01) and Graves' disease (OR = 1.11, 95% CI 1.03–1.21, p < 0.01) were found to be risk factors for SS. Conclusion: Our results support a bidirectional causal relationship between SS and Hashimoto's thyroiditis and a positive correlation of genetically predicted Graves' disease on the risk of SS. [ABSTRACT FROM AUTHOR]

Graves’ disease (GD) is an autoimmune disease that can affect other tissues in addition to the thyroid gland. The clinical manifestations are a result of the impact of TSH receptor antibodies. Depending on the intensity of the immune response, in addition to hyperthyroidism, orbitopathy, dermatopathy and acropachy can also occur. Extrathyroidal manifestations of GD are most often the result of a more pronounced immune response. Dermatopathy is a rare extrathyroidal manifestation, with a prevalence of 0.5-4.3%, and when it occurs, it almost always accompanies orbitopathy (96%) and hyperthyroidism, while it is associated with a severe form of orbitopathy in 13-15% of cases. It is characteristic of long-standing disease and an intense autoimmune response. We present a case series of five patients with dysthyroid dermopathy. Our patients had different thyroid function disorders (hypo/hyperthyroidism), different forms of dermopathy, and varying times of onset during the disease. Association with orbitopathy and high TRAb concentrations were also present in all our patients. The effects of therapy applied for orbitopathy were monitored, which showed a favorable response on dermopathy, especially with the use of tocilizumab in some of our patients. [ABSTRACT FROM AUTHOR]

Background/Objectives: The thyroid gland has an important influence on the heart. Long-term exposure to high levels of thyroid hormones may lead to cardiac hypertrophy and dysfunction. The aim of the study was to evaluate the morphological and functional changes in the left ventricle in patients with hyperthyroidism caused by Graves' disease (GD) in comparison with healthy individuals, as well as to investigate potential differences in these parameters in GD patients in relation to the presence of orbitopathy. Methods: The prospective study included 39 patients with clinical manifestations and laboratory confirmation of GD and 35 healthy controls. All participants underwent a detailed echocardiographic examination. The groups were compared according to demographic characteristics (age and gender), heart rate and echocardiographic characteristics. Results: The patients with hyperthyroidism caused by GD had significantly higher values of left ventricular diameter, left ventricular volume and left ventricular mass compared to the healthy controls. In addition, hyperthyroidism significantly influenced the left ventricular contractility and led to the deterioration of the systolic and diastolic function, as shown together by longitudinal strain, color Doppler and tissue Doppler imaging. However, the patients with GD and orbitopathy showed better left ventricular function than those without orbitopathy. Conclusions: Besides the confirmation of previously known findings, our study indicates possible differences in echocardiographic parameters in GD patients in relation to the presence of orbitopathy. Further investigation with larger samples and meta-analyses of data focused on the evaluation of echocardiographic findings in the context of detailed biochemical and molecular analyses is required to confirm our preliminary results and their clinical significance. [ABSTRACT FROM AUTHOR]

Summary: Thyrotoxicosis leads to loss of bone mass. Vitamin D is important to bone health. In this randomized, placebo-controlled trial, we showed that bone restoration did not improve when adding vitamin D supplementation to standard care of Graves' disease thyrotoxicosis. Bone density and microarchitecture improved markedly with treatment of thyrotoxicosis. Purpose: Vitamin D is important to skeletal health and ensuring a replete vitamin D status is recommended. In thyrotoxicosis, bone turnover is increased and bone mass density (BMD) reduced. We examined whether vitamin D supplementation improves bone recovery in thyrotoxicosis caused by Graves' disease (GD). Methods: Using a double-blinded design, hyperthyroid patients with GD were randomized to vitamin D3 70 µg/day (2800 IU) or similar placebo as add-on to antithyroid drugs (ATD). At baseline and 9 months, we measured BMD and bone architecture using DXA and high resolution peripheral quantitative computerized tomography. Bone turnover markers (BTM) were measured at 3 months also. Effect of vitamin D versus placebo and the response to ATD treatment were analyzed using linear mixed modelling. Results: Eighty-six GD patients were included (age 41 ± 14 years, 86% females). Compared to placebo, vitamin D3 did not improve BMD or microarchitecture. In response to ATD, BMD increased in the hip by 2% (95%CI: 1–4%). Cortical porosity decreased in tibia (− 7% [95%CI: − 12 to − 2%]) and radius [− 14% [95%CI: − 24 to − 3%]), and trabecular thickness increased (tibia (5% [95%CI: 2 − 9%]) and radius (4% [95%CI: 1–7%]). Changes in BTM, but not thyroid hormones, were associated with changes in BMD by DXA and with changes in the cortical compartment. Conclusion: In newly diagnosed GD, 9 months of high dose vitamin D3 supplementation does not offer benefit by improving skeletal health. Treatment of thyrotoxicosis is associated with the recovery of BMD and microarchitecture. Clinicaltrial.gov identifier: NCT02384668 [ABSTRACT FROM AUTHOR]

Introduction: Lymphocyte depletion via anti-CD52 monoclonal antibody (mAb) therapy is an effective treatment strategy for relapsing–remitting multiple sclerosis (MS) but is associated with infusion/injection-associated reactions (IARs) and autoimmune-related adverse events (AEs). Gatralimab is a next-generation humanized anti-CD52 mAb. Methods: Two first-in-human trials were conducted in participants with progressive MS to assess the pharmacodynamics, pharmacokinetics, and safety of gatralimab administered via subcutaneous (SC) and intravenous (IV) routes, and to determine the effect of different comedication regimes on IARs to SC gatralimab. A Phase 1 trial (NCT02282826) included double-blind, placebo-controlled sequential ascending single IV (1, 3.5, and 12 mg) and SC (12, 36, and 60 mg) dose groups. A Phase 1b trial (NCT02977533) involved five groups who received SC gatralimab (36, 48, or 60 mg) and different comedications. A long-term safety (LTS) study (NCT02313285) examined safety and pharmacodynamics over 4 years. Results: Gatralimab produced depletion of lymphocytes (dose-dependently) and CD4+ regulatory T cells, with partial repopulation to normal values by approximately 12 months. Peak serum gatralimab concentrations followed dose-proportionality and were delayed by 6.0–7.5 days following SC administration. Treatment-emergent AEs, including IARs, were reported for most participants but were generally of mild or moderate severity, and treatment-emergent serious AEs were mostly MS-related. Methylprednisolone and antihistamine comedications were associated with reduced incidence of fevers and skin and subcutaneous tissue AEs, respectively. During the LTS study, one participant (3.0%) experienced an autoimmune-related AE (Basedow's disease), and subsequently died from pulmonary sepsis deemed unrelated to gatralimab by the investigator. Conclusions: These data show that gatralimab achieves the desired pharmacodynamic effect of lymphocyte depletion followed by repopulation, and has an acceptable safety profile, including low risk of non-MS autoimmunity. Although gatralimab is no longer in development for MS, insights from these trials may inform the development of comedication regimes of future anti-CD52 mAbs and subcutaneous formulations of other lymphocyte-depleting mAbs. Trial registration: NCT02282826, NCT02977533, NCT02313285. [ABSTRACT FROM AUTHOR]

Background: Selenium is a trace element crucial for thyroid function, and has potential therapeutic benefits in Graves' orbitopathy (GO). Therefore, we aim to evaluate its efficacy and safety in GO patients to provide valuable insights into its role as a therapeutic option for this condition. Design: Systematic review and meta‐analysis. Patients: GO Patients treated with selenium compared to placebo. Measurements: Clinical activity score (CAS), Graves' orbitopathy quality of life (GO‐QOL), eye symptoms and signs, and adverse events. Results: Out of 1684 records screened, four randomised controlled trials were included. Selenium was superior at 6 months in lowering the CAS (MD = −1.27, 95% confidence interval [CI] [−1.68, −0.85], p <.0001]), improving total GO‐QOL (RR = 2.54, 95% CI [1.69–3.81], p <.00001), and improving the visual and the psychological functioning scores (MD = 10.84, 95% CI [4.94–16.73], p =.003), (MD = 12.76, 95% CI [8.51–17.00], p <.00001) respectively. Similarly, it significantly improved these outcomes at 12 months. It also showed a significant decrease in the palpebral aperture at 6 months (MD = −1.49, 95% CI [−2.90, −0.08], p =.04). However, no significant differences were observed in proptosis, soft tissue involvement, ocular motility, and adverse effects. Conclusions: Selenium is effective in reducing CAS and improving the palpebral aperture and GO‐QOL in patients with GO. Additionally, it is safe and has promising therapeutic implications. However, further research is needed to validate its long‐term efficacy and safety. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A calculation analysis on the molecular structure and energy of 4-methyl-3-[2-(4-nitrophenyl)-1,3-dioxo-2,3-dihydro-1H-isoindole-5-amido]benzoic acid (COD30) is carried out with the 6-311G (d,p) basis set by the DFT/RB3LYP method as an anti-graves' disease treatment. The calculated FT-IR spectrum is strongly correlated with the vibrational spectra reported in the literature. To evaluate the entire electron density and organic reactive sites of COD30, molecular electrostatic potential (MEP) and frontier molecular orbitals (FMO) were analyzed. The density of states analysis is used to determine the orbital molecular contributions (DOS and PDOS). In comparison to methimazole (MMI) and propylthiouracil, COD30 showed more encouraging docking results, and it also offered golden binding contacts in addition to an improvement in docking energy (PTU). The outcomes of bioactivity prediction and MD simulation indicate that COD30 could be further developed into an inhibitor of Graves' disease. [ABSTRACT FROM AUTHOR]

Background Autonomously functioning thyroid nodules (AFTNs) constitute 5% to 7% of thyroid nodules and represent the second most common cause of hyperthyroidism following Graves' disease. Currently, radioactive iodine (RAI) and surgery are the standard treatment options, and both incur a risk of postprocedural hypothyroidism and other surgery and radiation-related complications. Methods This work aimed at assessing the efficacy of radiofrequency ablation (RFA) as an alternative treatment option for resolving hyperthyroidism and the nodule volume rate reduction (VRR) and its associated adverse events. Results A total of 22 patients underwent RFA for a solitary AFTN. Seventy-two percent (n = 16) had subclinical hyperthyroidism, 9% (n = 2) had overt hyperthyroidism, and 18% (n = 4) were biochemically euthyroid on antithyroid medication. Average pretreatment TSH was 0.41 mIU/L (SD = 0.98) and free T4 1.29 ng/dL (SD = 0.33). Following a single RFA session, hyperthyroidism resolved in 90.9% (n = 20) and average VRR (61.13%) was achieved within 3 to 6 months following the ablation. Except for 1 nodule, none of the nodules grew during the follow-up period (16.5 months). Two patients (9%) developed transient tachycardia requiring short-term beta-blocker therapy, and 2 developed mild hypothyroidism requiring levothyroxine therapy. Two patients developed recurrent hyperthyroidism and elected to undergo lobectomy and repeat RFA respectively. No serious adverse effects were noted in this cohort. Conclusion RAI and/or surgery represent the standard of care for toxic adenomas, but RFA shows excellent efficacy and safety profile. Therefore, at centers with RFA expertise, it should be considered an alternative treatment strategy, avoiding radiation and surgery-related complications. [ABSTRACT FROM AUTHOR]

Background: Graves' disease (GD) is an autoimmune disease associated with an increased incidence of other autoimmune diseases. To investigate the causality between GD and Diabetes mellitus (DM), we designed bidirectional two-sample Mendelian randomization (MR) and multivariable MR (MVMR) studies. Methods: Single-nucleotide polymorphisms (SNPs) associated with GD, thyroid peroxidase (TPO), thyroglobulin (Tg), thyroid-stimulating hormone (TSH), type 1 diabetes (T1D), and type 2 diabetes (T2D) were obtained from the IEU Open GWAS and FinnGen biobank databases. For the forward MR study, we used GD (sample size = 458,620) as the exposure and T1D (sample size = 520,580) and T2D (sample size = 211,766) as the outcomes. Next, high risk of T1D and T2D were used as exposure variables, and GD was used as the outcome variable for the reverse MR analysis. Finally, MVMR analysis was conducted to investigate the probable relationship between DM and indicators for thyroid function like TPO, Tg, and TSH. The inverse variance weighting (IVW) was used as the main method. Finally, the heterogeneity and sensitivity were assessed. Results: There were 27, 88, and 55 SNPs associated with GD, T1D, and T2D, respectively. A significant causal connection between higher genetic liability of GD and the risk of T2D (OR [95% CI] = 1.059 [1.025–1.095], P = 5.53e-04) was found in the forward MR analysis. Comparatively, the significant causal relationship between higher genetic liability of GD and the risk of T1D was not demonstrated (OR [95% CI] = 0.998[0.927,1.074], P=0.949). However, reverse MR suggested that there was a genetic susceptibility to T1D that increased the likelihood of developing GD (OR [95% CI] = 1.173[1.117,1.231], P = 1.913e-10), while T2D did not (OR [95% CI] = 0.963 [0.870–1.066], P = 0.468). Furthermore, there was inadequate evidence to suggest that abnormal TSH, TPO, and Tg levels increase the risk of incident T1D or T2D in individuals with GD. MVMR revealed no causal relationship among Tg, TSH, TPO, T1D, or T2D. Conclusion: There was no increased risk of T1D with an increase in genetic susceptibility to GD, although higher genetic susceptibility to T1D has been shown to be associated with increased risk of developing GD. A unidirectional causal relationship between the genetic liability for GD and increased risk of T2D was observed using MR analyses. MVMR analysis showed no statistically relevant causality between the genetic liability for TSH, TPO, or Tg and the risk of either T1D or T2D. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective To assess the effectiveness and safety of combining methylprednisolone with mycophenolate mofetil in managing moderate to severe active Graves' ophthalmopathy (GO), and to compare its efficacy against methylprednisolone monotherapy. Methods A retrospective study was conducted to select patients with moderate to severe active GO who received treatment at the Department of Endocrinology and Metabolism, Guizhou Medical University Affiliated Hospital, from January 2019 to January 2024. The patients were divided into two groups: a combination group receiving methylprednisolone combined with mycophenolate mofetil, and a monotherapy group receiving methylprednisolone alone. The objective was to compare changes in visual score, appearance score, clinical activity score (CAS), eye protrusion, eye fissure width, and eye movement between the two groups of patients while documenting any adverse events. Results A total of 98 patients were enrolled in the study, comprising 32 patients in the combination group and 61 patients in the monotherapy group. Both groups exhibited improvements in quality of life scores, CAS, and degree of protrusion following treatment compared to baseline. However, at the end of the 12-week treatment period, there was no statistically significant difference (P > 0.05) observed between the two groups regarding changes in visual scores, appearance scores, CAS, protrusion degree, fissure width, and proportion of reduced eye movement before and after treatment. Notably though, the combined therapy group demonstrated a significantly higher improvement rate for pain relief and reduction of eyelid congestion during eye movement when compared to the monotherapy group (P < 0.001). At the endpoint of treatment, there were no statistically significant differences in appearance score, protrusion degree, tear width, and reduction in eye movement between the two groups before and after treatment (P > 0.05). The combination group exhibited higher visual scores and greater improvement in CAS compared to the monotherapy group (P < 0.05), along with a higher rate of eyelid edema improvement (P < 0.05). At 12 weeks, the monotherapy group had an effective rate of 65.0%, while the combination group had an effective rate of 66.7%. By week 24, the combined group achieved an effective rate of 80.0%. The overall effectiveness at week 12 and treatment endpoints did not show any statistically significant differences between the two groups (P > 0.05). No cases of leukopenia or severe infection occurred in the combination group. Conclusions The combination therapy of methylprednisolone and mycophenolate mofetil demonstrates efficacy, tolerability, and safety in the treatment of moderate to severe active GO. While the overall effectiveness of this combination may not surpass that of hormone therapy alone, it exhibits potential superiority in improving visual scores, eyelid congestion, eyelid edema, and eye movement pain when compared to hormone therapy alone. [ABSTRACT FROM AUTHOR]

Objective: The utilization of radioactive iodine‐131I (RAI) has long been established as a cost‐effective and conventional treatment for managing Graves' disease (GD). However, the accurate prediction of the clinical response to RAI treatment remains difficult. The successful resolution of GD through RAI therapy is typically characterized by the induction of hypothyroidism or euthyroidism. Thus, the principal aim of this study was to identify plausible predictors of RAI efficacy in the treatment of GD. Methods: The clinical data of 613 GD patients, who underwent RAI treatment for the first time, were retrospectively analyzed, including age, gender, duration of hyperthyroidism, presence or absence of ocular signs, thyroid volume, thyroid weight, thyroid function (FT3, FT4, and TSH), radioactive iodine uptake (RAIU) at 2 h/6 h/24 h (2‐h/6‐h/24‐h RAIU) prior to RAI treatment, the highest RAIU (RAIUmax), and administered activity of 131I and 131I activity per gram of thyroid tissue. Success of RAI treatment was defined as achieving hypothyroidism or euthyroidism for more than 1 year after the initial treatment. Univariate and multivariate logistics regression analyses were conducted to identify factors that influence the efficacy of RAI treatment for GD. And at last, based on the results of the multivariate logistic regression analysis, a nomogram model was established. Results: In this study, the success rate of RAI treatment for GD was 91.2% (559/613). Univariate analysis demonstrated that several factors, including age (p = 0.005), thyroid volume (p = 0.001), thyroid‐stimulating hormone (TSH, p = 0.042), ratio of RAIU at 6 h to 24 h (6‐h/24‐h RAIU, p = 0.048), total 131I activity (p = 0.026), and 131I activity per gram of thyroid tissue (p = 0.001), were significantly associated with treatment outcome. Multivariate logistic regression analysis indicated thyroid volume and 131I activity per gram of thyroid tissue as significant independent predictors of radioactive iodine therapy (RIT) efficacy. The area under the ROC curve of the established nomogram model was 0.769 (95% confidence interval [CI]: 0.692–0.846), indicating that the model has good discriminatory ability. Conclusion: Calculated‐dose RAI is effective in the treatment of GD. The smaller thyroid volume and the higher 131I activity per gram of thyroid tissue are predictors of RAI efficacy in the treatment of GD. [ABSTRACT FROM AUTHOR]

Objective: The relationship between post-traumatic stress disorder (PTSD) and autoimmune thyroid disease (AITD) needs further evaluation. This study employs Mendelian randomization (MR) to investigate the causal correlations of PTSD with autoimmune thyroiditis (AIT) and Graves' disease (GD). Methods: Datasets for PTSD, AIT, and GD were obtained from FinnGen. The exposure-outcome causal relationship was assessed using inverse variance weighted, MR-Egger, and weighted median. Horizontal pleiotropy was evaluated through the MR-Egger intercept, heterogeneity was examined using Cochran's Q test, and robustness was assessed via leave-one-out sensitivity analysis. Results: MR analysis indicated no significant causal relationship between PTSD and AIT (OR 0.920, 95% CI 0.832 to 1.017, p = 0.103), but a potential increase in the risk of GD associated with PTSD (OR 1.056, 95% CI 1.008 to 1.105, p = 0.021). MR-Egger intercept showed no horizontal pleiotropy (p > 0.05), and Cochran's Q showed no heterogeneity (p > 0.05). Sensitivity analysis suggested the MR results were robust. Conclusions: Evidence of an MR association between genetic liability to PTSD and an increased risk of GD were provided, but no evidence of association between PTSD and AIT. The findings indicate that individuals with PTSD may have an increased likelihood of developing GD, underscoring the importance of further research to comprehend the intricate interplay between PTSD and thyroid disorders. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the association of IL-27 serum level and IL-27 gene SNP rs153109 with the risk and clinical features of the Iraqi patients with AITD. The blood samples were collected from 120 AITD patients and 60 healthy controls. Serum levels of interleukin-27 were assessed using ELISA kit. The study results showed a higher significant difference of IL-27 in sera of AITD patients compered to controls (p<0.001). The allele frequency and genotypes in the patient and control groups were determined using Highresolution melting (HRM) to detect the genetic variation in IL-27 gene SNP (rs153109). the result showed that CC and TC genotype of rs153109 had a statistically significant increased frequency in GD patients compared to controls (OR=19.4, P-value =0.0002), (OR=2.9, p-value =0.011). while the CC genotype of rs153109 was found to be more common in HT patients than control (OR = 6.8, value=0.017). In conclusion, the study suggested that genetic polymorphism of IL-27 gene rs153109 may be associated with AITD risk among Iraqi population. [ABSTRACT FROM AUTHOR]

Thyroid eye disease (TED) is the most common symptoms of Graves' disease. This condition commonly manifests bilaterally and symmetrically. The most prominent symptoms are lid retraction, exophthalmos and diplopia. Rarely, individuals with Graves' disease show asymmetrical or unilateral eye symptoms. Marine-Lenhart syndrome is a variant of Graves' disease with occasional hyperactive nodules. A 36-year-old male patient presented to the endocrinology outpatient department at a tertiary care hospital in Muscat, Oman, in 2022 with unilateral eye proptosis and was subsequently found to have Graves' disease. This case presents a rare Graves' disease variant with unilateral goiter and orbitopathy. [ABSTRACT FROM AUTHOR]

Thyrotoxicosis appears to be a predisposing factor for cerebral venous thrombosis (CVT), which is a rare but important cause of stroke in young adults. The presentation of CVT is highly variable, ranging from a history of headaches (in the majority of cases) to deep coma, with the latter requiring invasive neurosurgical decompression. Although the long-term outcomes of CVT are favorable, multicenter cohort studies have shown that death may occur in up to 4% of cases in the acute phase and 8–10% of cases in the long term. It has been argued that the substantial decrease in mortality in patients with CVT that has been observed during the past few decades may be the result of an increased awareness of CVT among clinicians. Given that thyrotoxicosis is a risk factor for CVT, clinicians (and endocrinologists) should be alert to the possibility of CVT in patients with thyroid disease in order to prevent it whenever possible or treat it promptly. In this review, we provide an updated overview of the characteristics of patients with thyrotoxicosis who presented with CVT, the underlying mechanisms, and a few tips for clinicians. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

This study aimed to explore the molecular mechanism of neuronal cell adhesion molecule (NrCAM) by regulating Th17 cell differentiation in the pathogenesis of Graves' disease (GD). Naïve CD4+ T cells were isolated from peripheral blood mononuclear cells of GD patients and healthy control (HC) subjects. During the differentiation of CD4+ T cells into Th17 cells, NrCAM level in GD group was improved. Interference with NrCAM in CD4+ T cells of GD patients decreased the percentage of Th17 cells. NrCAM overexpression in CD4+ T cells of HC subjects increased the percentage of Th17 cells and upregulated p‐IκBα, p50, p65, c‐Rel protein expressions, and NF‐κB inhibitor BAY11‐7082 partially reversed NrCAM effect. NrCAM overexpression promoted the degradation of IκBα, and overexpression of small ubiquitin‐related modifier 1 (SUMO‐1) inhibited IκBα degradation. NrCAM overexpression reduced IκBα binding to SUMO‐1. During Th17 cell differentiation in HC group, NrCAM overexpression increased IL‐21 levels and secretion, and IL‐21 neutralizing antibody reversed this effect. IL‐21 level was decreased after p65 interference in CD4+ T cells of HC subjects. p65 interacts with IL‐21 promoter region. In conclusion, NrCAM binds to SUMO‐1 and increases phosphorylation of IκBα, leading to activation of NF‐κB pathway, which promotes Th17 cell differentiation. [ABSTRACT FROM AUTHOR]

Context Thyrotoxicosis requires accurate and expeditious differentiation between Graves' disease (GD) and thyroiditis to ensure effective treatment decisions. Objective This study aimed to develop a machine learning algorithm using ultrasonography and Doppler images to differentiate thyrotoxicosis subtypes, with a focus on GD. Methods This study included patients who initially presented with thyrotoxicosis and underwent thyroid ultrasonography at a single tertiary hospital. A total of 7719 ultrasonography images from 351 patients with GD and 2980 images from 136 patients with thyroiditis were used. Data augmentation techniques were applied to enhance the algorithm's performance. Two deep learning models, Xception and EfficientNetB0_2, were employed. Performance metrics such as accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and F1 score were calculated for both models. Image preprocessing, neural network model generation, and neural network training results verification were performed using DEEP:PHI® platform. Results The Xception model achieved 84.94% accuracy, 89.26% sensitivity, 73.17% specificity, 90.06% PPV, 71.43% NPV, and an F1 score of 89.66 for the diagnosis of GD. The EfficientNetB0_2 model exhibited 85.31% accuracy, 90.28% sensitivity, 71.78% specificity, 89.71% PPV, 73.05% NPV, and an F1 score of 89.99. Conclusion Machine learning models based on ultrasound and Doppler images showed promising results with high accuracy and sensitivity in differentiating GD from thyroiditis. [ABSTRACT FROM AUTHOR]

It has been reported that Graves’ disease (GD) sometimes improves spontaneously during pregnancy, although exacerbation of GD during postpartum period or relapse of hyperthyroidism caused by GD might occur. This study aimed to investigate the incidence of postpartum diagnosis of thyroid eye disease (TED) in relation to thyroid dysfunction. This retrospective cross-sectional study enrolled 11,104 deliveries from the patients with GD between January 2004 and August 2022. Within the 12-month postpartum period, 72 patients (0.65%) were diagnosed with TED. The thyroid function of the 72 patients comprised 9 remission, 13 continued antithyroid medicine, and 50 thyroid dysfunction; 30 newly diagnosed GD, 1 hypothyroidism, and 19 relapse/recurrence of GD. In the 49 patients with thyroid dysfunction, no difference was observed in the median values of thyroid-stimulating hormone (TSH) receptor antibody (TRAb) and TSH receptor stimulating antibody between the TED diagnosis and the development of hyperthyroidism. However, when the patients were classified into the newly developed GD and relapse/recurrence of GD groups, the difference became significant and the TRAb level was high in the newly developed GD (16.1 vs. 5.0 IU/L, p < 0.0001, and 15.0 vs. 6.0 IU/L, p = 0.0003). Thyroid dysfunction preceded TED diagnosis in more than half of the patients and the median time for each event was 6.5 vs. 8.1 months. The active phase TED was observed in 8 of the 72 patients. Of the 72 patients newly diagnosed with TED in postpartum, two-thirds were accompanied by thyroid dysfunction and 8 of them were in active phase.

A 55-year-old woman transitioned from hypothyroidism to Graves’ disease (GD) and then developed thyroid eye disease (TED) with proptosis and diplopia. After three cycles of daily methylprednisolone pulse therapy, her condition progressed to dysthyroid optic neuropathy with decreased visual acuity in both eyes. Her clinical activity score (CAS) was 7 points. Orbital magnetic resonance imaging (MRI) showed that the enlarged extraocular muscles were compressing the optic nerve in the area of the cones. Although her visual acuity recovered during two further cycles of daily pulse therapy, disease activity persisted for 4 years. TED exacerbated five times. Each time, the patient received weekly pulse therapy with no adverse reactions until her ophthalmopathy was relieved. The total cumulative dose of methylprednisolone was 59.5 g. Thyroid-stimulating antibody (TSAb) was positive from the time of hypothyroidism onset and became strongly positive with the onset of GD and the progress of TED. In addition, MRI was useful for the evaluation of the pathophysiology of ophthalmopathy. This case report suggests that careful monitoring by both endocrinologists and ophthalmologists using CAS, ophthalmological assessments, TSAb measurement, and orbital MRI are useful for making treatment decisions for TED.

Almost a century has passed since Plummer reported the efficacy of short-term preoperative inorganic iodine therapy for Graves’ disease in the 1920s. Since there were concerns about the escape phenomenon and exacerbation with inorganic iodine, antithyroid drugs became the mainstay of pharmacotherapy for Graves’ disease following their development in the 1940s. With regard to long-term inorganic iodine monotherapy, Trousseau reported a case in the 1860s, and several subsequent reports suggested its efficacy. Around 1930, Thompson et al. published a number of papers and concluded that long-term inorganic iodine monotherapy was useful if limited to mild cases under careful follow-up. From Japan, in 1970, Nagataki et al. reported that, of 12 patients treated with inorganic iodine, three remained eumetabolic for more than two years. Since 2014, some reports have also been published from Japan. A summary of these recent reports is given below. The starting dose of potassium iodide is around 50 mg/day, and candidate responders have mild disease, with FT4

Abstract Background Microwave ablation is a new, minimally invasive technique for the treatment of thyroid nodules. Hyperthyroidism due to destructive thyroiditis is a known risk of microwave ablation, though it occurs in only a minority of cases. We report a rare case of a patient diagnosed with Graves’ disease nearly six months after undergoing microwave ablation of a thyroid nodule. Case presentation On July 31, 2022, a 43-year-old male patient presented to our hospital with symptoms of pyrexia, excessive sweating, and palpitations lasting for 15 days. History inquiry revealed that the patient had undergone microwave ablation of right-sided thyroid nodule nearly five months ago at another hospital. The patient’s thyroid ultrasound suggested bilateral diffuse thyroid lesions, with a moderately echogenic mass observed on the right side of the thyroid gland, potentially indicative of thyroid nodule ablation. The patient had elevated serum thyroid hormone levels, decreased thyroid-stimulating hormone levels and positive associated thyroid antibodies. To control the symptoms of hyperthyroidism, the patient opted for oral antithyroid medication, and thyroid hormonal levels returned to normal after 3 months of treatment. The patient is now under regular follow-up. Conclusions In this case, we presented the onset of Graves’ disease following microwave ablation in a patient with subclinical thyroid autoimmunity. While the causal relationship between microwave ablation and Graves’ disease remains unproven, this case suggests that preexisting autoimmune thyroid conditions may increase susceptibility to postoperative thyroid dysfunction. Procedural factors, such as thermal injury to surrounding tissues and potential involvement of the autonomic nervous system, are also potential contributors to the development of Graves’ disease following microwave ablation.

Background: Hyperthyroidism, or Graves’ disease (GD), is the consequence of an overproduction of thyroid hormones. Objective: This study aimed to determine the concentration of soluble CD23 in GD patients and the correlation of its level with biomarkers (T.3, T.4, thyroid stimulating hormone [TSH], FT.3, FT.4, and vitamin D, among those. Materials and Methods: There were eighty patients (50 patients with hyperthyroidism and 30 controls), during the time frame beginning in February 2021 and ending in April 2022 at Karbala city. In this research, participants were required to have a positive result on both an ultrasound of the thyroid and a test for thyrotropin receptor autoantibody (TRAB). FT.3, FT.4, and TRAB. Levels were determined by the VIDAS technique. Serum sCD23 and vitamin D3 levels were determined by ELISA using commercial test kits. Results: The mean age of the patients included in this study was 39 ± 12 years, while that of the control group was 30 ± 10 years. GD was noticed among female more than male patients. Regarding the age groups of GD, more patients were in the 25–44 years age group than in the other age groups. The immunological marker sCD23 is higher in the patients’ group when compared with the control group (486.16 ± 185.39, 166.64 ± 61.15, respectively) and no correlation between levels of it and T3, T4, TSH, and vitamin D. Conclusion: There was a statistically significant difference between the patient and control groups in the levels of sCD23 and thyroid panel test.

Background: Thyroid gland lesions are common and can result from systemic conditions such as Graves’ disease or localized abnormalities like nodular enlargement or tumors. Thyroid malignancies are the most prevalent endocrine cancers, accounting for approximately 92% of all endocrine malignancies. This study aims to explore the spectrum of thyroid neoplasms in a tertiary healthcare center. Aims and Objectives: The primary objective of this study was to examine the histopathological spectrum of thyroid neoplasms in a tertiary healthcare center. Additionally, the study aims to assess the frequency of various thyroid neoplasms across different age groups and genders and to identify any associated nonneoplastic thyroid lesions that occur alongside thyroid neoplasms. Materials and Methods: This observational descriptive cross-sectional study was conducted in the Department of Pathology, Pt. Jawahar Lal Nehru Memorial Medical College, Raipur, Chhattisgarh, India, over 50 months from January 2020 to March 2024. A total of 71 cases meeting the inclusion criteria were analyzed. Results: Of the 71 thyroid specimens examined, 12 cases (16.9%) were benign, whereas 59 cases (83.09%) were malignant. The study demonstrated a significant female predominance with a female-to-male ratio of 9.1:1 (64 females and 7 males). Most cases were observed in the 21–30 years age group, with a mean age of 32.3 years. Papillary carcinoma was identified as the most common malignant lesion, accounting for 35 cases (52.1%), whereas follicular adenoma was the most common benign lesion, accounting for 9 cases (12.7%). Conclusion: Accurate diagnosis of thyroid malignancies requires a combination of clinical history, radiological imaging, thyroid function tests, and thorough histopathological examination. Early and proper diagnosis facilitates more effective treatment decisions, standardized management protocols, and improved patient outcomes.

Graves’ disease commonly presents with thyroid and extrathyroid manifestations. Cardiovascular manifestations are present in 6% of patients. Only 1% of patients has dilated cardiomyopathy and acute heart failure, which is an unusual presentation of Graves’ disease. An elderly male patient presented with acute heart failure, atrial fibrillation, renal impairment, and secondary to hypotension, diagnosed with dilated cardiomyopathy and significant left ventricular (LV) dysfunction. His test results revealed an increase in T3 and T4 levels with a low thyroid-stimulating hormone (TSH), as well as positive antithyroid antibodies and TSH receptor antibodies, confirming Graves’ disease. The patient improved symptomatically with antiheart failure treatment and antithyroid drugs. On follow-up, his LV dysfunction completely recovered. This instance emphasizes the need of screening heart failure patients to identify reversible causes of heart failure and provide suitable treatment.

Background: Signal transducer and activator of transcription 6 (STAT6) is an important nuclear transcription factor. Previous studies demonstrated that blocking STAT6 can ameliorate thyroid function by reducing serum T3 and T4. Sodium/iodide symporter (NIS) is a key protein that mediates active iodine uptake and plays an important role in regulating thyroid function. This study explored the interaction between STAT6 and NIS. Methods: Immunohistochemical staining was performed for detecting the expression of NIS in different tissues. RT-PCR was performed for evaluating the mRNA level of NIS when Nthy-ori 3-1 cells were incubated with IL4, thyroid stimulating hormone (TSH), or monoclonal thyroid-specific stimulatory autoantibody (TSAb) for 24 h. Quantitative RT-PCR, western blot, and immunofluorescence analysis were performed for detecting NIS expression after inhibiting STAT6 phosphorylation by AS1517499. Finally, we used luciferase reporter assays to explore the ability of STAT6 to regulate the promoter activity of the NIS-coding gene. Results: NIS was highly expressed in thyroid epithelial cells of EAGD mice or Graves’ disease (GD) patients, and TSAb increased the expression of NIS. We show that a STAT6 phosphorylation inhibitor can attenuate the effect of TSAb on increasing NIS protein and mRNA levels. Finally, we confirm that transcription factor STAT6 can mediate NIS transcription and co-activator P100 protein can enhance STAT6-dependent transcriptional activation. Conclusion: In GD, TSAb induces STAT6 signaling to upregulate NIS expression, and STAT6 blockade ameliorates thyroid function via downregulation of the NIS. Our study furthers understanding of the effects of STAT6 on thyroid function and reveals new avenues for GD treatment.

Objectives: The pathogenesis of Graves’ orbitopathy (GO) remains to be fully elucidated. Here, we reviewed the role of genetics and epigenetics. Design: We conducted a PubMed search with the following keywords: GO, thyroid eye disease; or Graves’ ophthalmopathy; or thyroid-associated ophthalmopathy; and: genetic, or epigenetic, or gene expression, or gene mutation, or gene variant, or gene polymorphism, or DNA methylation, or DNA acetylation. Articles in which whole DNA and/or RNA sequencing, proteome, and methylome analyses were performed were chosen. Results: The different prevalence of GO in the two sexes, as well as racial differences, suggest that genetics play a role in GO pathogenesis. In addition, the long-lasting phenotype of GO and patient-derived orbital fibroblasts suggests a genetic or epigenetic mechanism. Although no genes have been found to confer a specific risk for GO, differential gene expression has been reported in orbital fibroblasts from GO patients vs control fibroblasts, suggesting that an epigenetic mechanism may be involved. In this regard, a different degree of DNA methylation, which affects gene expression, has been found between GO and control fibroblasts, which was confirmed by whole methylome analysis. Histone acetylation and deacetylation, which also affect gene expression, remain to be investigated. Conclusions: Although no pathogenic gene variants have been reported, epigenetic mechanisms elicited by an initial autoimmune insult seem to be needed for differential gene expression to occur and, thus, for GO to develop and persist over time.