Search Results (294)

Background: Thyroid eye disease (TED) is a rare autoimmune orbital disorder predominantly associated with Graves’ disease. It is characterized by orbital inflammation, tissue remodeling, and potential visual morbidity. Conventional therapies, particularly systemic glucocorticoids, offer only partial symptomatic relief, failing to reverse chronic structural changes such as proptosis and diplopia, and are associated with substantial adverse effects. This review aims to synthesize recent developments in understandings of TED pathogenesis and to critically evaluate emerging therapeutic strategies. Methods: A systematic literature review was conducted using MEDLINE, Embase, and international clinical trial registries focusing on pivotal clinical trials and investigational therapies targeting core molecular pathways involved in TED. Results: Current evidence suggests that TED pathogenesis is primarily driven by the autoimmune activation of orbital fibroblasts (OFs) through thyrotropin receptor (TSH-R) and insulin-like growth factor-1 receptor (IGF-1R) signaling. Teprotumumab, a monoclonal IGF-1R inhibitor and the first therapy approved by the U.S. Food and Drug Administration for TED, has demonstrated substantial clinical benefit, including improvements in proptosis, diplopia, and quality of life. However, concerns remain regarding relapse rates and treatment-associated adverse events, particularly hearing impairment. Investigational therapies, including next-generation IGF-1R inhibitors, small-molecule antagonists, TSH-R inhibitors, neonatal Fc receptor (FcRn) blockers, cytokine-targeting agents, and gene-based interventions, are under development. These novel approaches aim to address both inflammatory and fibrotic components of TED. Conclusions: Teprotumumab has changed TED management but sustained control and toxicity reduction remain challenges. Future therapies should focus on targeted, mechanism-based, personalized approaches to improve long-term outcomes and patient quality of life. Full article

This study reports the use of single-cell RNA sequencing to evaluate B cells in the peripheral blood mononuclear cells (PBMCs) and intrathyroidal blood mononuclear cells of patients with Graves’ disease (GD) undergoing thyroidectomy. These cells were stimulated with overlapping peptides of thyroid autoantigens, including thyroid-stimulating hormone receptor (TSHR), thyroglobulin (Tg), and thyroid peroxidase (TPO). In PBMCs, naive B cells are characterized by IL6 and CXCR5, whereas memory B cells express IGHG1, IGHG2, and CD74. HLA-DMA, HLA-DRB1, IGHG, IGHM, CD74, CD79A, and MS4A1 expression increased in peptide-stimulated naive and memory B cells compared to those in the controls. Thyroid naive B cells are characterized by CD40 and TNFRSF13C, whereas memory B cells express IGHM, CD79A, and MS4A1. Thyroid B cells showed higher DUSP1, DUSP2, CD69, FOSB, RGS1, and immunoglobulin gene expression than control PBMCs and thyroid cells. B-cell receptor analysis revealed frequent IGHV3-23 and IGHV4-34 usage in controls, whereas IGHV4-34/IGHJ4 expression was increased in TSHR-stimulated groups. We concluded that B-cell responses to TSHR, Tg, and TPO differed and that changes in B-cell reactivity also occurred in PBMCs and the thyroid. Additionally, IGHV3-23 and IGHV4-34 may be associated with autoantibody production in GD. Full article

Thyroid eye disease (TED) is a complex autoimmune disorder characterized by orbital inflammation and tissue remodeling. Teprotumumab, a fully human monoclonal antibody targeting insulin-like growth factor-1 receptor (IGF-1R), represents a significant breakthrough in TED treatment. This review comprehensively analyzes the therapeutic role of teprotumumab in TED management. Mechanistically, teprotumumab inhibits the IGF-1R/TSHR signaling complex, thereby reducing orbital fibroblast differentiation and inflammatory responses. Phase II and III clinical trials have demonstrated its remarkable efficacy in reducing proptosis and improving clinical activity scores, with the benefits extending to both active and chronic TED cases. Real-world studies have validated these findings further and expanded its potential applications to various clinical scenarios, including dysthyroid optic neuropathy and steroid-resistant cases. However, several challenges remain. These include treatment-related adverse effects such as hyperglycemia and hearing impairment, with emerging evidence suggesting ethnic variations in susceptibility. The high cost of treatment poses significant accessibility barriers, while limited long-term follow-up data and potential disease recurrence necessitate further investigation. This review synthesizes the current evidence to inform clinical decision-making and highlights areas requiring additional research to optimize teprotumumab’s therapeutic application in TED management. Full article

Cholestyramine, a bile acid sequestrant, has been used primarily for lipid-lowering purposes but has also shown potential in managing hyperthyroidism and thyrotoxicosis. The objective of this review is to assess the efficacy, safety, and clinical indications of cholestyramine in the treatment of hyperthyroidism, thyrotoxicosis, and associated conditions, particularly when conventional therapies fail or are contraindicated. A literature review of clinical guidelines, original research articles, and case reports was conducted, focusing on studies that explored cholestyramine’s use in the treatment of hyperthyroidism, thyrotoxicosis, and levothyroxine overdose. Cholestyramine has demonstrated effectiveness in rapidly reducing thyroid hormone levels in these conditions. Studies indicates that cholestyramine accelerates the reduction of T3 and T4 levels when used as adjunctive therapy alongside standard treatments, particularly in severe or refractory cases. Evidence from case reports also supports its utility in managing conditions such as amiodarone-induced thyrotoxicosis, thyroid storm, and preparation for thyroidectomy. However, the long-term effectiveness of cholestyramine remains uncertain, with potential challenges regarding gastrointestinal side effects and medication interactions. Further studies are needed to integrate it more widely into clinical guidelines for the management of thyroid disorders. Full article

Background: Diagnostic delay and error represent pervasive problems in healthcare with grave implications for treatment and prognosis. Though characteristic of human cognition, cognitive biases commonly contribute to delays in the physician decision-making process, particularly in atypical or complex presentations in youth. Methods: We present a case series of three adolescent athletes with varied clinical presentations whose diagnostic conceptualization and treatment were delayed in part due to cognitive biases with consequences for overall health and development, as well as return to sport. Results: The first case depicts how an atypical presentation of celiac disease was attributed to growing pains, illustrating the contribution of anchoring bias and confirmation bias in medical decision making. The second case represents the misattribution of chronic exertional compartment syndrome pain to growing pains and post-exercise soreness, highlighting the influence of ascertainment bias on the initial misdiagnosis. The third case describes how a vertebral mass was misdiagnosed as a left shoulder strain from weightlifting, depicting the contribution of anchoring bias and ascertainment bias in medical decision making. Conclusions: Early recognition of cognitive biases, including confirmation bias, anchoring bias, and ascertainment bias, is crucial for improving medical decision making, particularly in cases of rare or atypical presentations, reducing unnecessary diagnostic delays, and setting more realistic patient expectations. Through discussion of these cases, we highlight concrete steps to manage bias to facilitate timely diagnosis within the primary care and sports medicine setting. Full article

Background: Brain tumors are among the most difficult diseases to deal with in modern medicine due to the uncontrolled cell proliferation, which causes grave damage to the nervous system. Brain tumors can be broadly classified into two categories: primary tumors, which originate within the brain, and secondary tumors, which are metastatic in nature. Effective glioma, meningioma, and pituitary tumor diagnosis and treatment requires the precise differentiation of these tumors as well as non-tumors for improved clinical outcomes. Methods: Here, we present a new method to classify brain tumors based on the MobileNetV2 architecture with advanced preprocessing for high accuracy. We accessed an MRI image dataset from Kaggle that contained 1311 images in the test set. We split the data into 80% training and 20% testing. All images underwent extensive preprocessing, including grayscale conversion, noise removal, and contrast-limited-adaptive-histogram equalization (CLAHE). All images were resized to 224 × 224 pixels. Using transfer learning, the baseline frozen layers were kept intact while the top layers were trained with a learning rate of 0.0001, which was tuned to the model’s requirements using early stopping to avoid overfitting. Results: With the outlined methodology, we obtained an astounding accuracy of 99.16%, including strong performance in the no-tumor category, where recall rates were approaching 100% and false positive rates were minimized. Conclusions: These findings strongly indicate that the application of lightweight convolutional neural networks in diagnostic imaging can considerably expedite accurate brain tumor identification by radiologists. Full article

Thyroid organoids, three-dimensional in vitro models derived from stem cells, have emerged as a powerful tool for studying thyroid development, function, and disease mechanisms. These organoids recapitulate the key aspects of the thyroid gland, including the follicular structure, hormone production, and response to stimuli such as to the thyroid-stimulating hormone (TSH). Recent advances in thyroid organoid technology have established the basis for the modeling of development and thyroid diseases, including congenital hypothyroidism (CH), autoimmune conditions like Graves’ disease and Hashimoto’s thyroiditis, and other thyroid-related disorders. By utilizing pluripotent stem cells (PSCs) and adult tissue, researchers have generated organoid models suitable for dissecting the mechanisms associated with thyroid development while mimicking the genetic, functional, and inflammatory characteristics of thyroid diseases. Additionally, thyroid organoids offer the potential for personalized medicine by providing a platform to test therapies in a more clinically relevant context. This review highlights the recent progress in thyroid organoid generation, discusses their applications in dissecting the thyroid development mechanisms and disease modeling, and explores their potential for advancing our understanding of the thyroid physiology and pathology. Furthermore, we address the challenges and future directions in the optimization and use of thyroid organoids in translational research. Full article

A 49-year-old female presented for nuclear medicine diagnostics of a sonographically suspected parathyroid adenoma dorsal to the cranial pole of the right thyroid lobe. The patient received Tc-99m-pertechnetate and Tc-99m-sestamibi (including SPECT/CT) scans, revealing no sestamibi uptake by the suspected parathyroid adenoma but a ventrally adjacent autonomous thyroid adenoma. Additional F-18-ethylcholine-PET/CT as well as subsequent Tc-99m-sestamibi-SPECT/US and F-18-ethylcholine-PET/US fusion imaging confirmed the suspected diagnosis of simultaneous autonomous thyroid adenoma and parathyroid adenoma. A blood analysis showed additional Graves’ disease. Full article

Objectives: The aim of this study was to find correlations between vitamin D deficiency and thyroid autoimmune pathology in a group of patients from Dobrogea, a non-endemic geographical area, with a high degree of sunshine. An important factor in maintaining immunological balance is the intake of an adequate level of vitamin D. Multiple studies have suggested that vitamin D deficiency is associated with a higher incidence of autoimmune diseases. Recent studies have analyzed the possible effect of this factor in promoting autoimmunity, as the serum level of BAFF often increases among patients with systemic autoimmune diseases. Methods: This study included 80 patients with autoimmune thyroid pathology from the Dobrogea area. The entire study group (n = 80) was divided according to the established diagnosis into two study groups: Group 1 included 62 patients with CAT (chronic autoimmune thyroiditis), and Group 2 included 18 patients with GD (Graves’ disease). Results: Vitamin D study average values of 25-OH-vitamin D found statistically significant differences between vitamin D values in the two groups (p = 0.018). Determination of BAFF (B-cell-activating factor) serum levels among patients with CAT and GD obtained a lower mean value of BAFF for the CAT group compared with the GD group. The evolution of BAFF serum level related to the serum levels of the antithyroid antibodies ATPO (antithyroidperoxidase) and ATG (antithyroglobulin) was also analyzed. In the patients with GD, BAFF was not correlated with the value of ATPO or ATG, but in the patients with CAT, a correlation was found between the value of BAFF and the level of ATG but not the ATPO level. Conclusions: This study analyzed BAFF serum levels in patients with CAT and GD. The results indicate that BAFF acts as a stimulatory factor of immunoglobulin production in autoimmune diseases. These results require clarifying the role and therapeutic benefits of supplementing vitamin D intake in patients with autoimmune diseases. Full article

Current therapies for Graves’ disease (GD) primarily aim to manage hyperthyroidism through synthetic antithyroid drugs, radioiodine, or surgery. However, these approaches are often limited by their incomplete efficacy and the risk of inducing hypothyroidism. The latest advances in understanding the autoimmune mechanisms driving GD have paved the way for novel therapies targeting the thyrotropin receptor (TSH-R) or immune pathways. Overall, key targets include cluster of differentiation 20 (CD20), cluster of differentiation 40 (CD40), protein tyrosine phosphatase non-receptor type 22 (PTPN22), cytotoxic T lymphocyte antigen-4 (CTLA-4), B cell-activating factor (BAFF), and the Fc receptor-like protein 3 (FcRL3). Recent preclinical studies and clinical trials testing targeted therapies have shown promising results in terms of efficacy and safety. Here, we present a narrative review of the literature on emerging therapeutic approaches for GD that are currently under investigation. Full article

Background/Objectives: We aimed to explore long-term trajectories of thyroid-stimulating hormone receptor antibody (TRAb) in patients with Graves’ disease (GD) and to identify key factors associated with TRAb normalization. We also investigated whether these trajectories correlate with Graves’ orbitopathy (GO) comorbidity. Methods: We retrospectively reviewed 403 patients with GD who had an initial TRAb level ≥ 1.5 IU/L between 2010 and 2021, monitoring their TRAb levels for at least 3 years. K-means clustering was performed to categorize patients into distinct TRAb change patterns (A, B, C, D). We employed a Cox regression–based time-to-event model, expressing results as “Survival ratio” rather than the conventional Hazard ratio, to reflect the proportion of patients achieving TRAb normalization over time. Key variables included age, sex, initial TRAb, and GO comorbidity. Results: Four unique TRAb patterns emerged, differing primarily in baseline TRAb levels, duration of GD, and treatment approaches. Pattern A demonstrated the highest TRAb normalization rate (96%), whereas Patterns B (80%), C (29%), and D (13%) showed lower probabilities. Regrouping into A vs. BCD further emphasized the distinct normalization profile of Pattern A. A higher “Survival ratio” was observed in female patients and those with baseline TRAb < 6.14 IU/L. In contrast, patients whose TRAb levels were ≥6.14 IU/L frequently exhibited persistently elevated values over a decade. GO comorbidity did not significantly differ among the four patterns. Conclusions: K-means clustering revealed four unique TRAb change patterns in GD, with baseline TRAb (stratified by the median of 6.14 IU/L) and sex emerging as significant predictors of normalization. These findings highlight the importance of early TRAb monitoring and tailored therapeutic strategies, particularly for those with persistently elevated TRAb levels. Full article

Graves’ disease (GD) is an autoimmune disorder that can be difficult to distinguish from other diseases due to symptom similarity. The exacerbation of GD owing to delayed diagnosis is a serious issue, and a novel accessible health screening system is needed. Therefore, this study investigated the association between GD and thyroid hormone levels in women’s hair and evaluated the prediction accuracy of this non-invasive type of sample. By optimizing pretreatment and analysis techniques using liquid chromatography–mass spectrometry (LC-MS), free triiodothyronine (FT3) and thyroxine (FT4) could be detected in only 2 mg of hair with high sensitivity. Compared with healthy controls, the thyroid hormone levels in the hair of GD patients were significantly higher in correlation with blood levels. The predictive ability of hair thyroid hormones was analyzed using a receiver operating characteristic (ROC) curve, and the optimal cut-off value was determined via the Youden index. As a result, the area under the curve (AUC) was 0.974 (95% confidence interval (CI): 0.935–1.000) for FT3 and 0.900 (95% CI: 0.807–0.993) for FT4. The cut-off value was 0.133 pg/mg (sensitivity: 91.2%; specificity: 100%; positive predictive value (PPV): 100%; negative predictive value (NPV): 76.9%) for FT3 and 0.067 pg/mg (sensitivity: 70.6%; specificity: 100%; PPV: 100%; NPV: 50.0%) for FT4. Collectively, our new approach offers the possibility of accurately and non-invasively detecting GD using hair samples. Since hair can be stored and transported at room temperature, this system facilitates large-scale screening at locations including hair salons and homes, potentially enabling the early determination of GD outside of medical facilities. Full article

Graves’ disease and hyperthyroidism in women with childbearing potential are a challenge in pre-conceptional counseling. The non-surgical alternatives are radioiodine therapy or antithyroid drugs. Here, we focus on the TSH receptor antibody (TRAb) level—without or after radioiodine therapy—and the probability of fetal or neonatal hyperthyroidism. This immunological effect should be weighed against the risk of congenital malformation taking propylthiouracil during pregnancy. For up to 2 years after radioiodine therapy for Graves’ disease, TRAb levels may remain above the pre-therapeutic level. The time of conception after radioiodine therapy and a high TRAb level are associated with the likelihood of neonatal hyperthyroidism: 8.8% probability if conception occurred 6–12 months after radioiodine therapy, with a 5.5% probability for 12–18 months, and 3.6% probability for 18–24 months. The TRAb value above 10 U/L in the third trimester is the main risk factor for neonatal hyperthyroidism. If a woman does not wish to postpone her family planning, the pre-conceptional counseling has to describe the risk of propylthiouracil, thiamazole, or of an uncontrolled hyperthyroidism. According to some national cohort studies (Danish, Swedish, Korean), the risk for fetal malformations (ear, urinary tract) under propylthiouracil is increased by 1.1–1.6%, in addition to the spontaneous risk for unexposed pregnant women. For thiamazole, the additional risk for fetal malformation was about 2–3%, depending on the dose of thiamazole. Propylthiouracil has posed a lower risk for congenital malformation than an uncontrolled hyperthyroidism. To minimize the risk for the newborn, women with Graves’ disease and hyperthyroidism should offer a definitive therapy strategy (e.g., radioiodine therapy) long before planning a pregnancy. Full article

Objectives: We investigate the correlation between functional and morphological changes in extraocular muscles (EOMs) and intraocular pressure (IOP) changes before and after thyroid eye disease (TED) treatment. Methods: A multicenter study with a retrospective chart review was conducted. Patients with active TED receiving corticosteroid therapy without glaucoma eye drops between 2014 and 2023 were reviewed. Various parameters were measured by magnetic resonance imaging. The primary outcome measure was the correlation between changes in the IOP and the cross-sectional area (CSA) of the EOMs before and after treatment. Secondary outcome measures were comparisons of IOP, the signal intensity ratio (SIR) of the EOMs and orbital fatty tissue (OFT), and the CSA of the EOMs before and after treatment. Results: The IOP in 99 eyes in 51 patients significantly decreased from 18 ± 3.4 mmHg to 15.5 ± 2.9 mmHg before and after treatment (p < 0.01)). The CSA and SIR of all EOMs and OFT significantly decreased after treatment (p < 0.05). Factors that had a significant positive correlation with the IOP change rate before and after treatment were the CSA change rate of the inferior rectus muscle (IRM) before and after treatment (Spearman’s correlation coefficient, R² = 0.24, p < 0.05) and the CSA change rate of the total EOMs before and after treatment (Spearman’s correlation coefficient, R² = 0.22, p < 0.05). Conclusions: In TED patients, IOP decreased with anti-inflammatory treatment alone. The most significant parameter that correlated with the decrease in IOP was the CSA change rate of the IRM. Full article

Background: Peripheral artery disease (PAD) is a high-risk vascular condition, and vascular remodeling has become a promising therapeutic approach. Paeoniflorin (PF) is the main bioactive compound in the roots of Paeonia lactiflora Pall, which is commonly used to treat a range of cardiovascular disorders. However, the mechanisms underlying the ameliorating effects of PF on PAD remain unclear. Therefore, the purpose of this study was to explore the therapeutic efficiency of PF on PAD and determine its mechanisms. Methods: The blood flow of mice was detected with a laser Doppler dot scanning imaging system. HE staining was used to observe the morphological changes of ischemic muscle. The changes in the serologic indexes were detected with an automatic biochemical assay, and the capillary density of ischemic gastrocnemius was detected with a Lectin immunofluorescence assay. The expression of angiogenesis-related proteins in ischemic gastrocnemius was detected with Western blotting, and the proportion of macrophages and neutrophils in total cells was detected with flow cytometry. Results: PF significantly increased blood flow, capillary density and protein expressions of vascular endothelial growth factor A (VEGFA), matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 2 (MMP9), and estrogen receptor α (ERα) in mouse ischemic tissue in a PAD model. PF enhances the migration of endothelial cells and promotes the formation of tubular structures, involving the ERα/ROCK2 signaling pathway. Furthermore, PF was found to promote the phenotypic transformation of macrophages and alleviated grave inflammatory responses during vascular remodeling. Conclusions: We determined that PF as a potent compound in promoting angiogenesis and mitigating inflammatory responses during revascularization. Full article