Search Results (312)

Objectives: Graves’ disease (GD) is the most common cause of hyperthyroidism and is associated with marked changes in body weight and body composition. Although weight loss is frequently reported, the extent and clinical relevance of body composition alterations, as well as their relationship with thyroid function, remain unclear. This study aimed to evaluate body composition and eating habits in patients with newly diagnosed hyperthyroid GD according to pre-morbid weight variation, and to compare these findings with those of matched euthyroid controls. Methods: Forty-four consecutive GD patients were enrolled and stratified based on the presence or absence of pre-morbid weight loss. Anthropometric measurements, thyroid function tests, thyroid volume, dietary habits (PREDIMED score, macronutrient intake and total daily caloric intake) and body composition assessed by bioelectrical impedance analysis (BIA) were collected. Standardized phase angle (SPA) and body cell mass index (BCMI) were calculated as nutritional indices. Body composition parameters and dietary adherence were compared with those of 44 age-, sex- and BMI-matched euthyroid controls. Results: Most GD patients (70.3%) reported weight loss before diagnosis; however, the magnitude of weight change did not correlate with the biochemical severity of thyrotoxicosis. Patients without weight loss showed higher fat mass percentage and higher caloric intake than those who lost weight. SPA was significantly associated with FT3, FT4 and TRAb levels, independently of age, sex, BMI and fat mass. Compared with controls, GD patients exhibited lower phase angle and SPA, higher extracellular water percentage and reduced BCMI, whereas fat mass and adherence to the Mediterranean diet were similar. Conclusions: Hyperthyroid GD patients display increased extracellular water and reduced body cell mass. SPA is inversely associated with GD severity and represents a valuable clinical tool for assessing nutritional status in thyrotoxic patients. Pre-morbid weight changes are not proportional to disease severity and may instead reflect increased caloric intake. Full article

Background and Objectives: Graves’ orbitopathy (GO) is an autoimmune disease that can cause severe visual dysfunction and cosmetic impairment. Pure endoscopic orbital decompression reduces proptosis with minimal external morbidity. However, studies integrating both objective outcomes and patient-reported quality of life remain limited. This study aimed to analyze objective and subjective outcomes of pure endoscopic orbital decompression in inactive GO. Materials and Methods: We retrospectively reviewed 20 consecutive patients with severe inactive GO who underwent pure endoscopic transnasal orbital decompression between 2020 and 2023. Proptosis was measured using Hertel exophthalmometry, and quality of life was assessed with the disease-specific GO-QoL (Graves’ Ophthalmopathy Quality of Life) questionnaire (functional and appearance subscales). Minimum follow-up was 12 months. Pre- and postoperative changes were compared using paired t tests. Results: A total of 26 orbits were operated on. Mean proptosis decreased by 3.85 mm (p < 0.001). GO-QoL improved in the functional (+3.27, p < 0.001) and appearance (+5.77, p < 0.001) subscales. No complications or new/worsened diplopia were observed. Conclusions: Pure endoscopic orbital decompression is a safe and effective technique to reduce proptosis in inactive GO. Although quality-of-life scores improved significantly, the clinical relevance may vary, highlighting the need to integrate objective outcomes and patient perception when evaluating surgical results. Full article

African swine fever virus (ASFV) is a highly contagious pathogen causing African swine fever in wild boars, warthogs and domestic pigs. The disease leads tosubstantial economic losses to the global pork industry and poses a grave threat to biodiversity. The early-encoded structural protein p22, owing to its immunodominant characteristics and high conservation across most genotypes, represents a promising diagnostic target and subunit vaccine candidate. In this study, the soluble extracellular domain of p22 protein (aa 30–177) was successfully expressed and purified, yielding 1.220 g/L. Eleven strains of monoclonal antibodies against p22 were generated, with four selected for B-cell epitope screening. Bioinformatic prediction-guided design was employed to generate overlapping truncations and peptides for epitope mapping. Based on those strategies, three novel linear B-cell epitopes were identified to be ³⁰KKQQPPKK³⁷, ¹³⁰WGTDDCTG¹³⁷ and ¹⁵⁰YVYNNPHH¹⁵⁷ by monoclonal antibodies. Sequence alignment across ASFV isolates revealed 100% evolutionary conservation in genotypes I/II, with minor variation in genotypes IV/VIII/XX/XXII. This study provided valuable data for broadening the ASFV antigen spectrum and identifying immunological targets for subunit vaccine formulation strategies. Full article

Background: Endocrine autoimmune diseases (AIDs) exhibit special polygenic characteristics in human leucocyte antigen (HLA) region. Current understanding of their association with lipid metabolism remains constrained by imprecise polygenic risk score (PRS) modeling. Advanced analytical approaches are needed to elucidate the association between genetic susceptibility and lipid metabolic dysregulation. Methods: We proposed a genetic distance-based clumping gPRS to account for linkage disequilibrium in the HLA region. gPRS and pathway gPRS were constructed for individuals diagnosed with type I diabetes (T1D), Graves’ disease (GD), Hashimoto thyroiditis (HT) and Addison’s disease (AD) in the UK Biobank, with sex considered as a stratification factor. Latent correlations between gPRS and phenotypes were explored using Kendall’s tau test, two-trait LD score regression (LDSC) and gene annotation. Results: Lipid metabolism served an important function through immune and inflammatory biomarkers across multiple traits. Males with low genetic risk tended to have lower high-density lipoprotein cholesterol level, while the correlation presented the opposite pattern in females. Increased genetic susceptibility to AIDs was associated with elevated levels of low-density lipoprotein cholesterol, triglycerides in low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) across all traits. Moreover, levels of polyunsaturated fatty acids, including omega-3 and omega-6, decreased with higher PRS in males and females, while those of monounsaturated fatty acids exhibited an increasing trend. Conclusion: Our study constructed more precise polygenic risk scores of AIDs, highlighting inflammation-mediated lipid metabolism as a potential pathogenic mechanism in endocrine AIDs, offering valuable insights into shared etiology for future comprehensive investigations. Full article

Background and Clinical Significance: Immune checkpoint inhibitors (ICIs), a revolutionary class of oncology therapeutics that enhance T cell-mediated antitumor immunity, are associated with various immune-related adverse events (IRAEs). While destructive thyroiditis and hypothyroidism are common, ICI-induced Graves’ disease (GD) is exceedingly rare, and the occurrence of concomitant Graves’ ophthalmopathy (GO) is even rarer. Case Presentation: A 57-year-old man with bladder cancer developed GO after receiving the first dose of the programmed death 1 (PD-1) inhibitor pembrolizumab. He presented with severe proptosis, extraocular muscle enlargement, hyperthyroidism, and significantly increased thyroid-stimulating hormone receptor autoantibodies (TRAb). Following the treatment with glucocorticoids and immunosuppressive therapy, his symptoms improved markedly but relapsed upon dosage reduction. To date, we have not identified any previous reports of GO with confirmed positive thyroid-related antibodies induced by pembrolizumab. Conclusions: This case offers valuable insights into the potential IRAEs, underscoring the importance of thorough clinical evaluation and early recognition to improve patient outcomes and quality of life. A literature review of ICI-induced GO was also performed, with further discussion of the potential pathogenic mechanisms, risk factors, and management strategies. Full article

Background and Objectives: While pemphigus vulgaris (PV) and bullous pemphigoid (BP) have been linked to autoimmune comorbidities, the spectrum and specificity of these associations remain uncertain. We aimed to investigate the prevalence and patterns of autoimmune diseases (AIDs) in patients with PV and BP compared with age- and sex-matched controls. Materials and Methods: We conducted a bicenter, retrospective case–control study including 287 PV patients with 1148 matched controls and 284 BP patients with 1137 matched controls. Autoimmune comorbidities were identified through medical record review, and disease-specific as well as system-level associations between PV, BP, and AIDs were assessed. Results: Overall AID prevalence was lower in PV (9.4%) and BP (8.1%) than in controls (18% and 15%, respectively; p < 0.001 and p = 0.002). PV was associated with Graves’ disease (adjusted OR: 3.16, 95% CI: 1.24–8.06), especially in females. BP was associated with Hashimoto thyroiditis (adjusted OR: 2.51, 95% CI: 1.33–4.75), particularly in males. System-level analyses revealed that cutaneous and multisystem AIDs were less frequent in both PV and BP (p < 0.001 for each and p = 0.001 for each, respectively), whereas endocrine AIDs were more frequent in BP (p = 0.038). Thyroid antibody positivity did not differ significantly between patients and controls. Limitations include retrospective design, possible overrepresentation of cutaneous AIDs in dermatology-based controls, and lack of external validation. Conclusions: Our findings suggest that PV and BP may be associated with selective, sex- and phenotype-specific autoimmune comorbidity patterns rather than a generalized autoimmune burden. Further prospective studies are needed to confirm these exploratory associations and clarify their temporal relationships. Full article

The use of highly active combined antiretroviral therapy (cART) has increased life expectancy in people living with HIV (PLWH). As a result of ongoing monitoring and surveillance in established HIV out-patient clinics, thyroid dysfunction amongst this population has become increasingly reported. In this narrative review, primary studies, case reports, and meta-analyses published on PubMed, Embase, and Cochrane were analysed. The most reported thyroid dysfunction is subclinical hypothyroidism (SCH). The prevalence of subclinical hypothyroidism was as high as 40% in PLWH with CD4 T-cell count < 350 cells/mm³, which is a level indicating a state of immunosuppression. Some less commonly reported thyroid dysfunctional conditions include overt hyperthyroidism and thyroid malignancy. Reports have linked the development of thyroid dysfunction to the use of cART, leading to immune reconstitution inflammatory syndrome (IRIS), which has also been linked to the development of Grave’s disease (GD). It is also important to check for thyroid malignancy, as PLWH are prone to having a high risk of developing non-AIDS-related or -defining cancer (NADC). Most research suggests symptom-driven monitoring. However, evidence also suggests that monitoring with cART status change, monitoring for patients with significant comorbidities, or with immune reconstitution may be useful. The screening should include Free Thyroxine (FT4), triiodothyronine (FT3), and thyroid-stimulating hormone (TSH) testing. Furthermore, vigilance for Grave’s disease and performing thyroid antibody checks are advised, especially once the reconstitution of T-cells is achieved. Full article

Background: Graves–Basedow disease (GBD) is an autoimmune thyroid disorder characterized by loss of tolerance to the thyrotropin receptor, with clinical manifestations such as a hyperadrenergic state, goiter, orbitopathy, and myxedema, inter alia. Selenium is a micronutrient, essential for the synthesis of selenoproteins. Selenium deficiency has been linked to an increased risk and exacerbation of GBD and GBD orbitopathy; therefore, it has been suggested that supplementation with this micronutrient could modify some outcomes associated with both conditions. Objectives: The objective of this scoping review was to synthesize and analyze the clinical trials that have evaluated the effectiveness of selenium on different outcomes in patients with GBD or GBD orbitopathy. Methods: The following databases were consulted: PubMed/Medline, Scopus, Biosis, ProQuest, Web of Science, and Google Scholar; and the search terms ‘Graves-Basedow disease’ or ‘Graves’ disease’ or ‘hyperthyroidism’ or ‘Graves’ hyperthyroidism’ or ‘selenium or selenium supplementation’ and ‘effectiveness’ were used. The search was limited to articles published in English between January 2000 and March 2025. To reduce selection bias, each article was reviewed independently by three authors using the Rayyan web tool and the JBI Critical Appraisal Checklist. Results: A total of 15 studies were identified (11 on patients with GBD and 4 on patients with GBD orbitopathy). In GBD, selenium supplementation was associated with significant improvements in TSH, FT4, FT3, TPOAb, TgAb, and TRAb levels; while in GBD orbitopathy, a positive effect of selenium supplementation was found on multiple clinical outcomes. Conclusions: Selenium supplementation in patients with GBD or GBD orbitopathy is associated with favorable biochemical and clinical outcomes. Full article

Background: Thyrotoxicosis is a systemic condition with well-documented cardiovascular effects, but its role as a precipitant of acute coronary syndromes (ACS) is often overlooked. This review summarizes clinical cases and original studies from the last 20 years, describing ACS triggered by thyrotoxicosis. Methods: Following PRISMA 2020 guidelines, we searched PubMed, Scopus, and Embase for reports published between 2004–2025. Only case reports and original articles were included. Data extracted included demographics, ECG findings, angiography results, thyroid function, etiology of hyperthyroidism, and outcomes. Results: A total of 35 cases were identified. The mean age was in the fourth decade of life, with a female predominance (57%, 20 out of 35). More than half of the patients presented with ST-segment elevation myocardial infarction (STEMI) or STEMI equivalents (21 out of 35; 60%). Electrocardiographic abnormalities most often involved anterior or inferior leads. Coronary angiography revealed normal vessels or diffuse vasospasm in 18 cases (51%), while thrombotic occlusion was observed in 4 cases (11%), spontaneous dissection in 2 cases (6%), and myocardial bridging in 3 cases (9%). The leading cause of thyrotoxicosis was Graves’ disease (≈65%), followed by painless thyroiditis, iatrogenic causes, and gestational hyperthyroidism. Thyroid storm was reported in approximately 20% of cases and was associated with malignant ventricular arrhythmias or sudden cardiac death. Conclusions: Thyrotoxicosis should be recognized as a rare but important trigger of ACS, especially in young patients without traditional risk factors. Pathophysiological mechanisms include coronary vasospasm, increased myocardial oxygen demand, and hypercoagulability. Early recognition may prevent unnecessary revascularization and optimize outcomes through integrated endocrine and cardiac management. Full article

Background: Achalasia is a rare primary esophageal motility disorder characterized by impaired lower esophageal sphincter relaxation and progressive loss of peristalsis. Although its pathogenesis remains incompletely understood, autoimmune mechanisms have been repeatedly proposed. Thyroid disorders, particularly autoimmune thyroiditis and Graves’ disease, have been reported as frequent comorbidities, suggesting a shared autoimmune background. Methods: We conducted a narrative review of PubMed, Scopus, and Web of Science from January 2005 to August 2025. Eligible studies included observational cohorts, case–control analyses, and case reports describing thyroid disease in achalasia. Mechanistic and immunological studies relevant to thyroid autoimmunity were also considered. Data were synthesized narratively and summarized in tables and figures. Results: Despite heterogeneity, evidence consistently indicates an increased prevalence of thyroid disease in achalasia. Early reports described dysfunction in up to one quarter of cases, while Romero-Hernández et al. demonstrated a threefold higher risk of autoimmune thyroid disease. Multicenter data confirmed thyroid autoimmunity in about one fifth of patients. Although thyroid disease did not alter short-term procedural outcomes, unrecognized dysfunction may complicate postoperative evaluation. Immunological findings, including human leukocyte antigen (HLA) susceptibility and lymphocytic infiltration of myenteric plexus, further support a shared autoimmune predisposition. Conclusions: Thyroid disorders, particularly autoimmune hypothyroidism, are more common in achalasia than in the general population. Although the evidence remains limited, the consistent signal suggests a non-random association. Early recognition may improve patient management, while prospective multicenter studies are needed to clarify causality and to determine whether achalasia should be considered part of a broader autoimmune spectrum. Full article

Background: Chronic autoimmune thyroiditis, also known as Hashimoto’s thyroiditis (HT) or chronic lymphocytic thyroiditis whose pathophysiology includes both cellular (T-cell mediated) and humoral (B-cell mediated) immune responses, leads to the destruction of thyroid follicular cells and progressive fibrosis of the thyroid gland. While hypothyroidism is a common autoimmune disease, athletes may experience unique challenges related to its diagnosis and management within the context of training programme, competition and anti-doping regulations. In turn, it is known that moderate physical exercise can have a positive effect on the immune system, while excessive exercise can cause unfavourable changes in this system. Therefore, we aimed (1) to identify the interplay between physical activity and autoimmune thyroid disease, (2) to quantify changes in thyroid function associated with physical activity, and (3) to explain the underlying mechanisms of autoimmune thyroiditis in athletes. Methods: The medical database PubMed/MEDLINE was searched in the time period 2004–2025, where 12 publications met the inclusion criteria and were ultimately included for further evaluation according to the RAMESES (Realist and Meta-narrative Evidence Syntheses: Evolving Standards). Results: The reviewed studies have clearly indicated that physical exercise has a beneficial effect on thyroid function, and two studies reported that non-excessive physical exercise leads to a decrease in TPO-Ab concentrations. Conclusions: The beneficial effect of physical exercise on thyroid function and immune response underlines the need for further well-designed studies to formulate specific guidelines for patients with HT, as well as for athletes with autoimmune thyroid disease. Similarly, there is a need to evaluate the prevalence of thyroid hormone use among amateur and professional athletes in order to establish prevention strategies. Full article

Background/Objectives: Thyroid disorders such as Hashimoto’s thyroiditis and Graves’ disease represent major endocrine challenges worldwide, often requiring long-term management. Recently, nutritional supplementation with selenium and myo-inositol has been proposed as a supportive strategy. This review aims to summarize the current evidence regarding their efficacy in improving thyroid function, reducing thyroid autoantibodies in Hashimoto’s disease, and restoring biochemical euthyroidism in Graves’ disease. Methods: A narrative review of the available literature was undertaken, concentrating on randomized controlled trials and observational studies evaluating selenium and myo-inositol, alone or in combination (MYO+Se), in patients with autoimmune thyroid disorders and benign thyroid nodules. Search Strategy and Study Selection: We searched MEDLINE/PubMed, Embase, Cochrane CENTRAL, and Scopus from inception to 31 July 2025. The search used Boolean operators to combine the following keywords: (“selenium” OR “selenomethionine”) AND (“myo-inositol” OR “inositol”) AND (thyroid OR Hashimoto* OR Graves’ OR hyperthyroid* OR hypothyroid* OR nodule* OR goiter OR orbitopathy). We included human studies in English. Inclusion criteria: Research designs include RCTs, quasi-experimental studies, cohort/case-control studies, and big case series (n ≥ 30). Exclusion criteria: Animal-only or in vitro studies (unless mechanistic), pediatric case reports, and editorials/commentaries. Study selection and data extraction: Two reviewers screened independently; discrepancies were settled through consensus. The data retrieved included the population, baseline iodine/selenium status (if reported), dose/formulation, treatment duration, outcomes (TSH, FT4, FT3, TPOAb, TgAb, TRAb, nodule metrics), and adverse events. Quality assessment: The risk of bias was assessed using the RoB-2 for RCTs and the Newcastle-Ottawa Scale or JBI checklists for observational studies. A qualitative synthesis emphasized study quality, consistency, directness, and accuracy. Results: Clinical research indicate that selenium supplementation may reduce thyroid peroxidase antibody (TPOAb) levels in Hashimoto’s disease, thereby attenuating autoimmune activity. Myo-inositol, particularly when combined with selenium, has been proven to improve thyroid hormone profiles while also lowering nodule size or growth. In Graves’ disease, supplementation has been linked to the restoration of biochemical euthyroidism in certain patients, albeit data are limited. Despite these encouraging results, diversity in trial design, treatment length, and dosages restrict the robustness of existing recommendations. Conclusions: Selenium and myo-inositol supplementation have shown promise as adjuvant treatments for autoimmune thyroid diseases and benign thyroid nodules. However, further large-scale, well-designed clinical trials are needed to determine the appropriate dosages, treatment duration, and patient selection criteria. Personalized supplementation solutions may improve medication efficacy and help with more comprehensive thyroid disease care. Full article

Mycotoxins, toxic fungal secondary metabolites, exhibit a diverse array of toxicological effects, including hepatotoxicity, carcinogenicity, estrogenicity, immunotoxicity, and neurotoxicity. These toxins cause severe contamination in food, feed, and traditional Chinese medicines (TCMs), threatening global food security and imposing substantial economic burdens. Among over 400 distinct mycotoxins identified to date, aflatoxin B1 (AFB1), ochratoxin A (OTA), and zearalenone (ZEN) stand out for their pervasive contamination and grave toxicities. Upon absorption, these toxins undergo biotransformation into reactive metabolites that exert multifaceted toxicities via mechanisms such as carcinogenesis, estrogenic effects, oxidative stress, inflammation, and abnormal apoptosis, collectively threatening human and livestock health. The application of natural and engineered enterosorbents suppresses intestinal absorption and subsequent bioactivation of mycotoxins, while dietary small-molecule bioactive compounds neutralize post-absorption toxicity via biotransformation intervention and cytoprotective reinforcement, collectively preventing the onset and progression of related diseases. This paper reviews the biosynthetic routes of three representative mycotoxins (AFB1, OTA, and ZEN), along with their biotransformation and underlying pathogenic mechanisms. Furthermore, nutritional intervention approaches targeting the underlying mechanisms to ameliorate mycotoxin-induced damage are discussed. This review not only provides valuable insights for future research on mycotoxin toxicity, but also establishes a theoretical foundation for utilizing dietary strategies to counteract mycotoxin-induced physical damage. Full article

Background: Safe, microbiome-based interventions for autoimmune hyperthyroidism are lacking. We isolated the lactic acid bacterium NES-428 from kimchi and previously demonstrated that it shares 99% 16S-rRNA identity with Lactobacillus brevis reference strains, confirming NES-428 as a novel strain. Here we evaluated its immunomodulatory and anti-thyroid activity in cellular and murine models. Methods: Jurkat T cells (5 × 10⁶) were incubated with heat-killed NES-428 for 24 h and subsequently stimulated with phorbol 12-myristate 13-acetate/ionomycin (50 ng mL⁻¹/1 µg mL⁻¹) for 6 h; cytokine transcripts were quantified by qRT-PCR. Hyperthyroidism was induced in female BALB/c mice by three intramuscular injections of adenovirus-encoding human TSH receptor (Ad-TSHR). Mice received a daily oral dose of NES-428 (1 × 10⁹ CFU) for 15 weeks. Serum thyroxine (T₄) levels, splenocyte cytokine secretion, and thyroid histopathology were assessed. Statistical analyses employed one-way ANOVA with Tukey post hoc or log-rank tests (α = 0.05). Results: NES-428 pre-conditioning of Jurkat cells significantly down-regulated IL-2 and IFN-γ transcripts (−48% and –43%, respectively; p < 0.01) compared with stimulated controls while modestly increasing IL-4 (+26%). In Ad-TSHR mice, daily NES-428 reduced mean serum T₄ from 11.2 ± 2.1 to 5.8 ± 1.4 µg dL⁻¹ (p < 0.001), restored body weight gain, and normalized follicular architecture relative to untreated hyperthyroid animals. NES-428 supplementation also lowered splenocyte IFN-γ secretion by 58% and raised IL-4 by 41% (p < 0.05). Conclusions: The kimchi-derived strain NES-428 attenuates Th1-skewed cytokine responses and ameliorates experimental hyperthyroidism in vivo. These findings support further investigation of NES-428 as a probiotic candidate for immune modulation in Graves’ disease. Full article

Background and Objectives: The pathogenesis of thyroid eye disease (TED) is driven by interactions between orbital fibroblasts and immune cells. Lymphocyte-activation gene 3 (LAG-3) is an immune checkpoint molecule with a similar structure to the T lymphocyte CD4 receptor but with higher affinity for MHC class II, and LAG-3–MHC class II interaction inhibits T lymphocyte activity. Lymphocytes shed LAG-3, generating soluble LAG-3 (sLAG-3), whose function is unclear. We investigated sLAG-3 involvement in Graves’ disease (GD) and GD-associated TED pathogenesis. Materials and Methods: Patients with GD-associated TED (n = 47) and GD without TED (n = 35) were enrolled alongside 37 healthy controls (HCs). Peripheral blood serum sLAG-3 levels were measured using enzyme-linked immunosorbent assays and compared across the three groups. The effect of intravenous glucocorticosteroid (IVGC) treatment (12 weeks) on sLAG-3 concentrations in patients with GD-associated TED was monitored, and associations of sLAG-3 levels with clinical characteristics were analyzed. Disease activity before and after IVGC treatment was assessed using Clinical Activity Score. Results: Relative to those in HCs, serum sLAG-3 levels were significantly higher in GD patients both with (p < 0.001) and without (p = 0.0129) TED. No significant difference in sLAG-3 levels was observed between the two patient groups (p = 1.000), and no significant change in sLAG-3 levels was detected in patients with TED after IVGC therapy (p = 0.0536). Conclusions: The higher sLAG-3 levels in patients compared to HCs suggest that sLAG-3 dysregulation may contribute to GD and GD with orbitopathy development and the pathomechanisms underlying these conditions. Metalloproteinase-mediated cleavage of LAG-3 from the lymphocyte surface enables T lymphocyte proliferation and activation, while released sLAG-3 may enhance the immune response. Further studies of sLAG-3’s mechanisms of action are needed to establish clear cut-off values and to define the diagnostic role of sLAG-3 in GD diagnosis. Full article