Regulatory T cells (Tregs) are key contributors to maintaining immune system stability, and their impairment has been linked to the pathogenesis of Graves' disease (GD). However, the precise molecular mechanisms driving Treg dysregulation in GD remain poorly understood. Our previous study identified a dysregulated long noncoding RNA, FOXP1-DT (forkhead box P1 divergent transcript), which might be related to Treg cells. This study aimed to investigate the role of FOXP1-DT in Tregs from individuals with GD. Fifteen patients diagnosed with GD and fifteen age- and sex-matched healthy controls were recruited. Our findings demonstrated that FOXP1-DT expression was markedly decreased in the peripheral blood mononuclear cells of GD patients and exhibited an inverse correlation with the concentration of thyroid-stimulating hormone receptor antibody. FOXP1-DT is mainly located in the nucleus and adjacent to the FOXP1 gene in the genome, a key transcription factor for Treg homeostasis. FOXP1 expression was also significantly reduced in GD patients and correlated positively with FOXP1-DT expression and Treg cell levels. Moreover, silencing FOXP1-DT reduced FOXP1 expression and Treg cell proportion, consistent with the clinical observation of a positive link between decreased FOXP1-DT expression and lower Treg frequency in GD patients. ROC curve analysis showed the potential biomarker value of FOXP1-DT in GD. These findings indicate that downregulated FOXP1-DT may be involved in the process of GD by regulating FOXP1-mediated Treg dyshomeostasis.

Paralysis to Analysis: Unmasking Thyrotoxic Periodic Paralysis in a Middle-Aged Male Patient With Undiagnosed Graves Disease

Graves' disease (GD) is an autoimmune disorder characterized by hyperthyroidism and a hypermetabolic state involving complex endocrine, metabolic, and immune interactions. Cocaine- and amphetamine-regulated transcript (CART) is a neuropeptide involved in energy balance, neuroendocrine signaling, and neuroimmune modulation; however, its circulating levels and clinical relevance in GD remain unclear. In this single-center prospective study, serum CART levels were evaluated in 44 patients with GD and 44 age- and sex-matched healthy controls. Associations with thyroid function, autoimmune markers, metabolic parameters, and thyroid ultrasound heterogeneity were analyzed. Serum CART concentrations were measured using an enzyme-linked immunosorbent assay, and clinical, biochemical, and ultrasonographic data were recorded. Serum CART levels did not differ significantly between GD patients and healthy controls. However, within the GD group, CART levels varied significantly according to thyroid ultrasound heterogeneity, with lower levels observed in patients with severe parenchymal heterogeneity. Serum CART levels showed positive correlations with body mass index and insulin resistance indices, while inverse correlations were observed with thyrotropin receptor antibody and anti-thyroid peroxidase antibody levels. No significant associations were identified between serum CART levels and circulating thyroid hormone concentrations. These findings suggest that serum CART may reflect metabolic and autoimmune heterogeneity rather than hypothalamic-pituitary-thyroid axis activity in GD, supporting its role as a context-sensitive, hypothesis-generating biomarker.

Association of NLRC3 gene polymorphism with Graves' disease susceptibility in a Southwest Chinese Han population.

A machine learning-based model for the prediction of thyroid eye disease with oxidative stress-related biomarkers.

Elevated lipid peroxidation biomarkers in autoimmune diseases: A systematic review and meta-analysis.

The coexistence of Graves' disease (GD) and papillary thyroid carcinoma (PTC) remains a subject of clinical debate. While PTC is frequently detected incidentally after thyroidectomy for GD, its prevalence, clinicopathological behavior, and preoperative predictors remain insufficiently defined. This single-center retrospective cohort study included 602 patients who underwent thyroidectomy between 2020 and 2025. Patients were categorized as: GD + PTC (n = 51); GD-only (n = 109); and PTC-only (n = 442). Demographic, biochemical, radiological, surgical, and pathological data were analyzed. Univariate and multivariate logistic regression models were used to identify factors associated with PTC development in GD. The prevalence of PTC among GD patients was 31.9%. Compared with sporadic PTC, GD-associated tumors were smaller (median 5mm vs. 12mm, p < 0.001) and demonstrated fewer aggressive features including lymphatic invasion, capsular invasion, multifocality, bilaterality, and nodal metastasis (all p < 0.01). GD + PTC patients were younger and showed a lower female predominance than those with sporadic PTC. When compared with GD-only patients, the GD + PTC group had significantly lower thyroid-stimulating Immunoglobulin (TSI) titers (median 3.8 vs. 7.65 IU/L, p = 0.007) and a higher prevalence of ultrasound-detected thyroid nodules (64.7% vs. 27.5%, p < 0.001). In multivariate analysis, only US-detected nodules (OR 3.56, p = 0.003) and lower TSI levels (OR 0.95, p = 0.03) independently predicted PTC in GD. PTC is relatively common among surgically treated GD patients, yet presents predominantly as microcarcinoma with less aggressive histopathological features. The presence of ultrasound-detected thyroid nodules was the strongest preoperative predictor of malignancy. These findings support careful and systematic ultrasonographic assessment in patients with GD, with FNAB guided by established ultrasound risk patterns, nodule size thresholds, and high-risk clinical features, rather than indiscriminate lowering of biopsy thresholds.

The aim of this study was to compare corneal and lens densitometry (CD and LD) values between active and inactive Graves Ophthalmopathy (GO) and Grave's Disease (GD) patients without ophthalmic involvement and healthy controls. This cross-sectional clinical study included 22 patients with active GO with bilateral ocular involvement (group 1), 36 patients with inactive GO (group 2), 54 patients with GD but without ophthalmopathy (group 3) and 30 age- and gender-matched healthy controls (group 4). All participants underwent comprehensive ophthalmic examination, followed by corneal and lens densitometry assessment using the Pentacam HR imaging system (Oculus Inc., Wetzlar, Germany). Comparative analysis revealed statistically significant differences (p < 0.05) in CD values among the groups across all layers, except for the anterior 10-12mm (p = 0.117), posterior 0-2mm (p = 0.185), and posterior 2-6mm zones (p = 0.099). Active GO patients showed the highest CD values, followed by inactive GO, non-ophthalmopathy GD patients, and healthy controls, respectively. Additionally, CD-mean, CD-SD and CD-max parameters showed statistically significant differences between the groups (all p < 0.05), with active GO demonstrating significantly higher values than other groups. Regarding LD, LD-mean, LD-SD, and LD-max values were significantly higher in all Grave's disease-related groups compared with the control group (p < 0.001). CONCLUSıON: Our study shows that lenticular and corneal clarity is significantly reduced in GO patients, especially during the active period. These findings suggest that Pentacam could be used as a rapid, reliable and non-invasive tool for the early detection of deterioration in corneal and lenticular transparency in these patients.

Abstract: Graves' disease (GD) is a disorder marked by an enlarged and overactive thyroid gland (Graves' hyperthyroidism), ocular abnormalities (Graves' orbitopathy; GO), and localized dermopathy (pretibial myxoedema; PTM). It is recognized as the most common cause of hyperthyroidism worldwide. Patients with GD most frequently exhibit elevated thyroid hormone secretion from thyroid cells as a result of autoantibodies acting as thyroid-stimulating hormone receptor (TSHR) agonists. Numerous investigations have examined the elements that contribute to the pathogenesis of GD, focusing on different components, such as molecular factors like non-coding RNAs (ncRNAs). NcRNAs represent a type of RNA transcript that, while not encoding proteins, are essential in the regulation of numerous aspects of cellular biology. NcRNAs include major groups, such as circular RNAs (circRNAs), long noncoding RNAs (lncRNAs), and small non-coding RNAs (sncRNAs), all of which are garnering increasing interest in the scientific community. This review will provide a comprehensive analysis of the function of ncRNAs in the development, diagnosis, and treatment of GD, and investigate the latest research in this area.

Neonatal fragment crystallizable receptor (FcRn) blockers selectively inhibit FcRn-mediated IgG recycling, resulting in degradation of IgG autoantibodies, including thyrotropin receptor autoantibodies (TSH-R-Ab). We describe a case involving a 55-year-old woman with a 17-month history of Graves' disease (GD) who was hyperthyroid despite 15 months on methimazole (MMI) 15-25 mg/day. She received the investigational FcRn blocker batoclimab in a clinical study and was subsequently followed in clinic. Within 1 week of starting weekly subcutaneous batoclimab, serum free triiodothyronine (FT3) and thyroxine (FT4) were normalized. Thyrotropin (TSH) was normal within 4 weeks. MMI was discontinued by study week 6. Twenty-three months after stopping batoclimab, the patient remained off MMI, with normal FT3, FT4, and TSH. Total IgG returned to approximate baseline levels 18 months post discontinuation of batoclimab, whereas TSH-R-Ab, which was elevated at baseline, remained below the upper limit of normal 23 months post batoclimab discontinuation. FcRn blockade may be an effective and potentially disease-modifying treatment for GD.

Monocytes are involved in autoimmune diseases, including Graves disease and thyroid eye disease (TED). We studied the expression and function of the thyrotropin receptor (TSHR) in all subsets (classical: CD14++, CD16-; intermediate: CD14++, CD16+; nonclassical: CD14+, CD16++), because the functional consequences of TSHR signaling induced by TSHR autoantibodies may contribute to TED. Flow cytometry was used to determine TSHR, intracellular IL-6 and IL-8, Akt phosphorylation, caspase 3, and reactive oxygen species production by monocytes from isolated peripheral blood mononuclear cells. Real-time polymerase chain reaction was used to measure mRNA of TSHR, IL-6, and IL-8 from enriched monocytes. Monocytes express TSHR, with expression induced by thyroid-stimulating hormone and Graves disease-specific autoantibody M22. Basal phosphorylated Akt levels were greater in monocytes from patients with TED. Thyrotropin receptor signaling was mediated through Akt. Monocytes produced reactive oxygen species and cytokines IL-6 and IL-8 in response to TSHR signaling. Cytokine expression was greater in classical and intermediate monocytes from patients with TED than those from healthy controls stimulated with thyroid-stimulating hormone and M22. Thyroid-stimulating hormone and M22 promoted apoptosis in intermediate and nonclassical monocytes but not classical monocytes. Apoptosis of nonclassical and intermediate monocytes appears mediated through caspase 3 since thyroid-stimulating hormone stimulated caspase 3 activation. Our results demonstrate functional TSHR on monocytes, and TSHR signaling stimulates proinflammatory cytokine and reactive oxygen species response, with increased response in monocytes from patients with TED. This suggests an important role for stimulatory autoantibodies-TSHR interaction in monocyte function and activation, which may be relevant to TED development.

Smoking is a recognised risk factor for Graves' disease (GD), but its quantitative relationship with disease severity, autoimmunity, and relapse after antithyroid drug (ATD) therapy is unclear. To evaluate the dose-dependent association between smoking exposure and key clinical outcomes in GD. Observational cohort study. Single-centre secondary-care endocrinology service in the United Kingdom. Consecutive adults with newly diagnosed GD confirmed by suppressed TSH, elevated thyroid hormones, and positive TRAb or diffusely increased scintigraphic uptake. All 991 eligible patients were included in baseline analyses; 663 completed ≥12 months follow-up after ATD cessation, and 712 contributed to long-term relapse analyses. Baseline TRAb and thyroid hormone levels, symptom score, presence of orbitopathy, ATD duration, and relapse at 12 months and long term, defined as recurrent biochemical hyperthyroidism with elevated TRAb after ATD withdrawal. Exposures were smoking status (non-, ex-, current smoker) and cigarettes/day. Current smokers (27%) had higher TRAb levels at diagnosis (median 7.8 vs 6.6 IU/L in non-smokers, p=0.002) and increased odds of orbitopathy (OR 1.76, 95% CI 1.17-2.64). Each 10 cigarettes/day conferred a 34% (95% CI 10-79%) higher odds of orbitopathy and 60% higher 12-month relapse risk. Smokers also had higher TRAb at ATD cessation. In time-dependent Cox models, excess relapse risk among current smokers was greatest early after ATD withdrawal (HR 1.24 at 6 months) and diminished by 2 years. TRAb mediated only 7% of the smoking-relapse association. Smoking is associated with greater autoimmune activity, higher orbitopathy risk, and increased relapse in a dose-dependent manner. Ex-smokers have risks comparable with non-smokers, supporting cessation or reduction as a meaningful intervention to improve GD outcomes.

A simplified figure displaying the main events leading to Hashimoto's thyroiditis and Grave's disease via Th1 and Th2 activation, and the potential sites of selenium (Se) action. (A) Activated by the dendritic cell, naïve helper T cells (CD4+ T cells) can mainly differentiate into two subsets, Th1 and Th2, which are crucial in orchestrating immune responses. Th1 cells produce tumor necrosis factor (TNF-a) along with interferon-γ (IFN-γ), exacerbating inflammation, in synergy with interleukin-6 (ΙL-6), leading to apoptosis (death of follicular cells). In parallel, oxidative stress induces activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway by reactive oxygen species (ROS) and the phosphorylation and degradation of NF-κB inhibitors, thereby allowing NF-κΒ to translocate to the nucleus. NF-κB acts in the nucleus as a master transcription factor in the nucleus, significantly increasing IL-6 production in various cell types. Se supplementation decreases IL-6 production, thereby mitigating the inflammatory process: it activates antioxidant enzymes and increases Treg cells, restoring the balance with Th17 cells. Th2, by producing interleukins, promotes B cell differentiation into plasma cells that produce massive amounts of IgG antibodies, which stimulate the TSH receptor on thyrocytes, promoting thyroid hyperplasia and hyperthyroidism. In mild thyroid eye disease (TED), Se abolishes the effects of oxidative stress in interorbital fibroblasts, reducing hyaluronic acid release, decreasing inflammation, and potentially lowering the production of glycosaminoglycans (GAGs). (B) Se enhances selenoprotein P (SELENOP) and glutathione peroxidase (GPX) activity; it is significantly involved in redox processes within the thyrocytes, scavenging H2O2, and its reactive by-products (e.g. hydroxyl radicals) through oxidation-reduction cycles. GPX neutralizes the hydrogen peroxide (H2O2) produced during thyroid hormone synthesis. This process is essential for maintaining a healthy balance (redox homeostasis) within the thyroid gland. The effects are inversely related to basal Se levels.

Definitive second-line treatment for pediatric Graves' disease (GD) includes radioiodine ablation (RAI) or thyroidectomy. The current treatment practice in pediatric GD patients is a contentious issue as the decision to consider either of the treatment options depends on preferences of patients, physicians, and access to surgical care and radioactive iodine treatment. This systematic review and meta-analysis were performed to compare the cure and relapse rates of RAI versus surgery as definitive therapy in children with Graves' Disease. A comprehensive search on Cochrane library, Embase, PUBMED, MEDLINE (via Pubmed), and ClinicalTrials.gov for English articles published on definitive treatment of GD in children since 1985 to 2023 was performed. The data were extracted and meta-analyzed for efficacy and safety outcomes, risk of bias (ROB), and certainty of evidence summated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) instrument. Twenty-nine (26 retrospective and 3 prospective) studies with a total of 1861 children and a mean age of 13.15years with a mean follow up of 8years were evaluated in the systematic review. Among these, 1061 children received RAI therapy, whereas 800 underwent thyroidectomy and were evaluated in the pooled analysis. 755 were excluded as details pertaining to definite treatment was not available. Studies were of low to moderate risk of bias. The pooled analysis suggests that RAI had significantly lower cure rate in children compared to children who underwent thyroidectomy (RR 0.89; 95% CI 0.81-0.99; p=0.03). In subgroup analysis of patients from 19 studies who underwent surgery, total thyroidectomy (2%) was more effective than subtotal thyroidectomy (13%) in preventing recurrent hyperthyroidism (p=0.001; moderate quality evidence). Hypothyroidism rates after RAI and surgery were similar (RR 0.97; 95% CI 0.67-1.40; p=0.88). There were no significant adverse outcomes reported such as secondary malignancy or quality of life after RAI. Following TT, adverse effects seen were permanent hypoparathyroidism (0.6%) and temporary recurrent laryngeal nerve palsy (5.1%). Thyroidectomy appears to be more effective than RAI in effecting cure in Graves' disease in children following failed remission with antithyroid medication therapy. However, access to thyroidectomy may not be universally available and RAI is an option in these children.

ObjectivesThis study aims to evaluate the analytical and clinical performance of the Abbott Alinity TRAb chemiluminescent microparticle immunoassay and establish the reference interval for healthy Chinese populations.MethodsThe precision, analytical sensitivity and linearity of Abbott TRAb assay were verified in accordance with the Clinical and Laboratory Standards Institute guidelines. A total of 300 samples from patients with Grave’s disease (GD) and other thyroid diseases were collected for method comparison and clinical performance verification. The performance of Abbott and Snibe TRAb assays was compared to Roche TRAb assay by correlation and agreement analysis. The diagnostic performance of Abbott TRAb assay was analyzed via receiver operating characteristic (ROC) analysis. The reference interval of Abbott TRAb was established from a cohort of 366 healthy individuals.ResultsThe Abbott Alinity TRAb assay demonstrated excellent precision, with repeatability (CV%) ranging from 1.04% to 5.92%, and within-laboratory imprecision (CV%) ranging from 1.09% to 5.92%. Manufacturer-claimed limits of blank, detection, and quantification were successfully verified. Linearity was confirmed from 1.14 to 47.72 IU/L. Strong correlation was observed between Abbott and Roche assays (Spearman r = 0.972; slope = 1.060), while Snibe and Roche assays showed lower correlation (r = 0.784). Concordance analysis showed the total agreement with Roche results were 97.7% for Abbott and 96.7% for Snibe. Diagnostic accuracy of the Abbott TRAb assay for GD was high, yielding an area under curve (AUC) of 0.999, sensitivity of 98.4%, and specificity of 99.4% at an optimal cutoff of 2.89 IU/L. The upper reference limits at 95th percentile and 97.5th percentile for healthy Chinese population using Abbott TRAb assay were 1.56 IU/L and 1.95 IU/L, respectively.ConclusionsThis study demonstrated the robustness of Abbott Alinity TRAb CMIA in clinical use with its verified analytical and clinical performance and established the reference interval for Chinese population.

This observational investigation aimed to assess the accuracy of a novel score in predicting the onset of overt Graves' orbitopathy (GO) in Graves' disease (GD) patients. A total of 156 consecutive GD patients without GO were enrolled. As control group, 45 patients with non-autoimmune hyperthyroidism were included. At baseline, an ophthalmological evaluation was performed, including 1) visual function tests; 2) orbital ultrasound. After 24 months, the occurrence of GO was assessed in all patients. At baseline, a score from 0 to 3 and a score from 0 to 5 were assigned based on the results of visual function tests and the results of orbital ultrasound, respectively. The scores were combined into an overall FUnctional and MOrphological risk score (FUMO score) (0-8 points), classifying patients as low risk (score 0-2) or medium-high risk (score 3-8). After 24 months, the two risk groups were compared for differences in: 1) presence/absence of GO; 2) GO activity and severity.Patients in the medium-high risk group developed overt GO more frequently than those in the low-risk group. Additionally, GO was more frequently active and moderate-to-severe in medium-high risk patients.Multiple logistic regression showed that TRAb levels and FUMO were the strongest independent predictors of GO, with higher FT3 and smoking habit levels also conferring increased risk. The model demonstrated good calibration and discrimination (AUC=0.84; p<0.0001), with high positive (73%) and negative (72%) predictive value. Subclinical ocular alterations can predict the progression of GO in patients with GD. The FUMO score, particularly when combined with TRAb and FT3 levels, reliably identifies patients at risk of developing overt GO, supporting its use for early risk stratification.

Epidemiology and Risk Factors of Hyperglycemic Events and Complications Among Patients with Graves' Disease (GD) or Thyroid Eye Disease (TED) in the United States.

The effect of iodine solution in total thyroidectomy for patients with Graves disease: A meta-analysis.

The necessity of total thyroidectomy for Graves' disease (GD) remains a subject of debate due to lifelong thyroxine replacement therapy. However, total thyroidectomy is a definitive treatment and allows for the detection of incidental thyroid cancer (ITC), which may necessitate further surgical intervention if not initially treated. This study aimed to investigate the prevalence, clinicopathological characteristics, and risk factors associated with ITC in GD patients undergoing total thyroidectomy. We conducted a retrospective cohort study of 86 GD patients who underwent total thyroidectomy from January 2016 to December 2022. Clinical and pathological characteristics were analyzed to determine potential risk factors associated with ITC. The incidence of ITC was 15.1% (13/86), predominantly papillary thyroid microcarcinoma (PTMC) at 9.3% (8/86). Patients with ITC were significantly older (mean age 45.2years vs. 36years, p = 0.017) and more frequently presented thyroid nodules on ultrasound (84.6% vs. 45.2%, p = 0.014). Multivariate analysis identified thyroid volume as a significant protective factor, with each 1mL increase reducing ITC risk by approximately 6% (p = 0.009). Older age, smaller thyroid volume, and the presence of thyroid nodules on ultrasound were significantly associated with increased ITC risk. A larger thyroid volume may be associated with a lower risk of ITC. Careful preoperative evaluation, including assessment of thyroid nodules on ultrasound, is advised in older patients and those with smaller glands. Surgical decisions should be guided by individual risk factors and shared decision-making.

Chronic thyrotoxic myopathy in an 81-year-old man with Graves disease.