Search Results (343)

Background and Clinical Significance: Carbimazole is a widely used medication to treat Graves’ disease, although it can rarely cause acquired aplastic anemia, a complication that happens in less than 0.01% of people. Case Presentation: We report a 36-year-old woman treated with supratherapeutic dose carbimazole who, after approximately six months of treatment, developed high grade fever, severe menorrhagia, spontaneous epistaxis, and pancytopenia. Her bone marrow biopsy showed severe bone marrow failure with only 5% cellularity and trilineage hypoplasia. Other potential causes were ruled out. Immediate discontinuation of carbimazole was done, and supportive care, including blood transfusions, broad-spectrum antibiotics, G-CSF, and eltrombopag, was started. The patient deteriorated during her hospital stay, developed neutropenic sepsis and acute respiratory failure from diffuse alveolar hemorrhage, which required intubation and pulse steroid therapy. She was stabilized and discharged, with a referral to a tertiary medical center for starting antithymocyte globulin (ATG) immunosuppressive therapy, which she subsequently completed; two months after discharge she was transfusion independent with near-normalization of her blood counts. Conclusions: This case serves as a stark reminder of how lethal thionamide-induced bone marrow failure can be, highlighting the vital need for immediate drug cessation, swift intensive care, and thorough patient education on early warning signs. Full article

Background: The relationship between Graves’ disease (GD) and thyroid carcinoma (TC) remains controversial, particularly regarding the predictive value of metabolic, hormonal, immunological, and ultrasound biomarkers. We performed a systematic review and meta-analysis to evaluate the prevalence of TC in patients with GD and to identify biomarkers associated with an increased risk of malignancy. Methods: A systematic literature search of PubMed/MEDLINE, Scopus, Web of Science, Embase, and the Cochrane Library was conducted in accordance with PRISMA 2020. Primary studies providing direct evidence in patients with Graves’ disease or indirect evidence concerning thyroid carcinoma-associated biomarkers were considered. Owing to substantial differences in study populations, designs, exposures, and outcomes, quantitative pooling was restricted to sufficiently comparable estimates, while the remaining evidence was synthesized descriptively. Results: Six primary studies were included. Two retrospective cohorts directly evaluated thyroid carcinoma in patients with Graves’ disease and included 1051 patients, of whom 317 had thyroid carcinoma. The remaining studies provided indirect evidence from patients with hyperthyroidism, population-based thyroid cancer cohorts, or genetic datasets. Because of substantial clinical and methodological heterogeneity, a single pooled estimate was not considered appropriate. Thyroid nodules and larger nodule size were associated with malignancy in Graves’ disease, while elevated triglycerides, reduced HDL cholesterol, and higher body mass index were associated with thyroid carcinoma in a surgically selected Graves’ disease cohort. Evidence concerning hormonal, immunological, inflammatory, and genetically determined metabolic markers was heterogeneous and largely indirect. Conclusions: Thyroid carcinoma risk in Graves’ disease is heterogeneous and appears to be concentrated in patients presenting with suspicious ultrasound findings and adverse metabolic profiles. Ultrasound biomarkers remain the most robust predictors of malignancy, while metabolic biomarkers represent promising complementary tools for individualized risk stratification. Current evidence does not support the routine use of hormonal or immunological biomarkers as independent predictors of thyroid carcinoma. Large prospective multicenter studies using standardized biomarker assessment are required to validate these findings and optimize personalized surveillance strategies. Full article

Graves’ disease is an autoimmune hyperthyroid disorder in which thyroid peroxidase (TPO) plays a central role in excessive thyroid hormone production. However, current TPO-targeting drugs, such as propylthiouracil, have limited selectivity and can cause serious adverse effects. In this study, we established an integrated discovery pipeline to identify and optimize novel small-molecule TPO inhibitors. The pipeline began with high-throughput screening of approximately 7000 compounds from the KRICT chemical library for peroxidase inhibition, followed by cytotoxicity filtering and iterative medicinal chemistry to generate NE-2 derivatives. Lead compounds (NE-2-6, NE-2-7, and NE-2-8) were evaluated using enzymatic assays, selectivity profiling against myeloperoxidase (MPO) and lactoperoxidase (LPO), molecular docking, plasma pharmacokinetic profiling, and in vivo antithyroid pharmacodynamic testing in an Ad-TSHR289-induced thyroid hyperfunction model. NE-2-6 exhibited potent TPO inhibitory activity and relative selectivity within the tested peroxidase panel. UV–visible spectral scanning and H₂O₂-dependent inhibition assays suggested that NE-2-6 perturbs the heme-associated catalytic environment of TPO; however, these data do not establish a definitive binding mode or kinetic inhibition mechanism. In the Ad-TSHR289-induced thyroid hyperfunction model, NE-2-6 reduced serum T4 levels, supporting antithyroid pharmacodynamic activity. Because autoimmune endpoints and dose-matched PK–PD relationships were not fully assessed, the findings should be interpreted as preliminary preclinical evidence supporting further evaluation of NE-2-6 as a TPO-targeting antithyroid candidate. Full article

Background and Clinical Significance: The co-occurrence of Hashimoto thyroiditis (HT), Graves’ disease (GD), and papillary thyroid carcinoma (PTC) is an extremely rare event and offers a unique opportunity to examine how chronic autoimmune thyroid disease may interact with the process of thyroid cancer development. Case Presentation: We present the case of a 42-year-old female with long-standing autoimmune thyroid disorders who developed progressive Graves’-related orbitopathy that did not improve with corticosteroid therapy. Owing to persistent hyperthyroidism and worsening orbital symptoms, she underwent total thyroidectomy. A histopathological examination of the removed thyroid gland surprisingly found PTC developing within a background of chronic autoimmune inflammation. The patient’s postoperative course included stable thyroid hormone replacement, a significant decrease in serum levels of thyroid autoantibodies, and clinical improvement in her orbital symptoms following decompressive surgery, although partial visual impairment persisted. Conclusions: This case highlights how chronic thyroid autoimmunity may create a carcinogenic environment and emphasizes the importance of comprehensive histopathological assessment and multidisciplinary care for patients with complex autoimmune thyroid disease. Full article

Background: Graves’ disease (GD) is an autoimmune disorder frequently associated with thyroid nodules, raising concerns regarding malignancy risk. However, reported cancer prevalence varies widely, and data from Eastern European populations remain limited. This study aimed to evaluate the risk of thyroid cancer in GD patients and to identify clinical predictors of malignancy. Methods: We conducted a retrospective cohort study including 168 patients diagnosed with GD between 2018 and 2022 at a tertiary referral center. Clinical, ultrasonographic, and histopathological data were analyzed. Associations between thyroid nodules and malignancy were assessed using chi-square tests and logistic regression analysis. Results: Thyroid nodules were identified in a substantial proportion of GD patients, and among patients with thyroid nodules who underwent thyroidectomy, thyroid carcinoma was confirmed by histopathological examination in 11 of 42 cases (26.2%). The presence of nodules was significantly associated with malignancy (OR = 4.337, 95% CI: 1.528–7.146, p < 0.001). Increasing age was independently associated with higher cancer risk (r = 0.221, p = 0.004). Papillary thyroid carcinoma (PTC) was the predominant histological subtype, most commonly presenting as early-stage disease (pT1aNxR0). Conclusions: Thyroid nodules were significantly associated with thyroid malignancy in patients with Graves’ disease. In this tertiary referral cohort, papillary thyroid carcinoma was the predominant histological subtype, supporting careful ultrasound evaluation and appropriate cytological assessment of thyroid nodules. Full article

Background: Postoperative haemorrhage (POH) is a rare but potentially life-threatening complication of thyroid surgery, with an incidence of 0.6–4%. Early identification of patients at increased risk is critical to guide perioperative management, especially in the context of evolving surgical practices and increasing demand for outpatient procedures. Methods: We conducted an explorative, retrospective, single-centre case–control study using a prospectively documented quality assurance dataset including 9158 thyroidectomies (2012–2019). POH requiring revision (n = 104) were compared to matched controls (n = 416; 1:4 ratio), matched by age, sex, type of procedure (uni- vs. bilateral), and year of surgery. Univariate analysis (Chi-square and t-test) was used to identify possible associations between candidate risk factors and POH. To supplement classical univariate statistics, we applied a Random Forest machine learning model to assess the relative importance of 25 potential variables derived from the clinical dataset based on previous literature. It was also planned to use the results to develop a proposal for a quantitative risk score, system, assigning weights to each factor (3, 1, or 0 points) depending on their relative importance for predicting POH. Patients were subsequently categorized into risk classes (low, intermediate, high) based on total point scores and reclassified. Results: High-impact risk factors confirmed in univariate analysis and Random Forest modelling included reoperative thyroidectomy, smoking, relevant comorbidities, medical treatment for hyperthyroidism and advanced age and were weighted with 3 points. Moderately associated variables such as regular alcohol consumption, Graves’ disease, hyperthyroid state at surgery, duration of the procedure and thyroid weight were weighted 1 point. Factors with negligible predictive value (e.g., BMI, gender, ASA classification) were assigned 0 points. The average score among patients without haemorrhage was 5.21, whereas the average score among patients with haemorrhage was 7.61. Within the matched study cohort, patients with POH accumulated higher risk scores than controls, suggesting potential discriminatory capacity. These findings formed the basis for the development of an exploratory three-stage ‘traffic light’ risk stratification model that requires external validation. Conclusions: A simple, interpretable point-based scoring system derived from a large matched case–control cohort identified key predictors of postoperative hemorrhage (POH) after thyroid surgery and enabled risk stratification within the study population. By combining conventional statistical methods with machine-learning approaches, the score may support individualized perioperative monitoring, surgical planning, and institutional resource allocation. However, because the model was developed using a 1:4 matched case–control design, it should be considered an exploratory risk stratification tool rather than a fully validated prediction model, and it does not directly estimate absolute POH risk or population incidence. External and prospective validation in large, representative multicentre cohorts (e.g., StuDoQ, HEDOS) is ongoing and will be required to establish calibration, generalizability, and clinical utility. Full article

Background: Graves’ disease is an autoimmune thyroid disorder that may be accompanied by systemic inflammation and Graves’ orbitopathy. This study evaluated the relationship between readily available hematological inflammatory markers and orbitopathy in patients with Graves’ disease. Methods: This retrospective observational study included 178 adult patients with Graves’ disease. Demographic, clinical, ophthalmological, and laboratory data were analyzed. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), monocyte-to-HDL cholesterol ratio (MHR), and C-reactive protein-to-albumin ratio (CAR) were calculated. Correlation, logistic regression, and ROC analyses were performed. Results: Among the 178 patients, 63 (35.4%) had Graves’ orbitopathy. Patients with orbitopathy had significantly higher NLR, PLR, SII, MHR, and CAR values than those without orbitopathy (all p < 0.001). Thyrotropin receptor antibody (TRAb) and thyroid-stimulating immunoglobulin (TSI) levels were positively correlated with all inflammatory markers. In multivariable logistic regression analysis, current smoking (OR 2.31, p = 0.047), TRAb (OR 1.08, p = 0.009), TSI (OR 1.06, p = 0.041), NLR (OR 1.63, p = 0.034), SII (OR 1.01, p = 0.018), MHR (OR 2.91, p = 0.012), and CAR (OR 3.84, p = 0.008) remained independently associated with Graves’ orbitopathy. Among the individual biomarkers, MHR showed the highest discriminative performance (AUC 0.818, 95% CI 0.754–0.882), while the combined inflammatory model achieved an AUC of 0.891 (95% CI 0.842–0.940), with an optimal predicted probability cut-off ≥ 0.43. Conclusions: Hematological inflammatory markers are associated with thyroid autoimmunity, disease activity, and Graves’ orbitopathy. These inexpensive and easily accessible markers may support clinical risk assessment in patients with Graves’ disease. Full article

Background: Selenium (Sel) supplementation has been proposed as an antioxidant adjunct in Graves’ orbitopathy (GO), with early randomized evidence suggesting benefits in quality of life (QoL), ocular involvement, and disease progression in mild GO. However, subsequent trials across populations with different Sel status and disease severity have yielded inconsistent findings. This systematic review and meta-analysis of randomized controlled trials (RCTs) reassessed the efficacy of Sel supplementation in GO. Methods: PubMed, Scopus, and the Cochrane Library were searched from inception to 1 May 2026 for RCTs, comparing Sel supplementation with placebo or no Sel supplementation in patients with GO (PROSPERO “CRD420261395074”). Heterogeneity was assessed using I² statistics and Cochran’s Q test. Risk ratios (RRs) were calculated using the Mantel–Haenszel method, and mean differences (MDs) using the Inverse-Variance method. Random-effects models with restricted maximum-likelihood estimation were applied. Results: Five RCTs including 303 patients were analyzed, of whom 165 (56%) received Sel. Sel supplementation was associated with a significant reduction in clinical activity score (MD −1.05; 95% CI −1.61 to −0.48; I² = 52%; p < 0.01). No significant differences were observed in palpebral aperture (MD −0.12; 95% CI −1.22 to 0.98; I² = 58%; p = 0.83), although this anatomical parameter should be interpreted cautiously because it may be influenced by thyroid functional status and hyperthyroidism-related Müller muscle hyperfunction. No significant differences were observed in QoL improvement (RR 1.72; 95% CI 0.43 to 6.92; I² = 86%; p = 0.24) or visual function (MD 6.31; 95% CI −1.40 to 14.03; I² = 45%; p = 0.11). Conclusions: Sel supplementation may improve clinical activity score in patients with Graves’ orbitopathy, but this finding should be interpreted cautiously given the small number of trials, limited sample size, and clinically relevant heterogeneity. Current evidence does not show consistent benefits for palpebral aperture, quality of life, or visual function. Larger RCTs stratified by baseline Sel status and disease severity are needed before firm conclusions can be drawn. Full article

Background/Objectives: Graves’ disease (GD) is a prevalent autoimmune thyroid disorder marked by thyrotoxicosis, goiter, and Graves’ orbitopathy (GO). Recent studies highlighted its association with dysbiosis. This systematic review aims to update the current literature and clarify the distinctive microbial signatures and dysbiosis associated with GD/GO. Methods: A systematic search for relevant studies was conducted across multiple databases (2000–2023), employing appropriate keywords. Relevant data were extracted from 25 eligible studies. Results: Microbiota analysis from 19 GD studies (713 patients, 546 controls) and eight GO studies (356 patients, 187 controls), primarily conducted in China (21/25), were examined. The gut microbiota richness and evenness were reduced in GD patients compared to controls in 62.5% of fecal samples. No consistent pattern in alpha diversity was observed in GO. Significant taxonomic divergence was observed between GD/GO and controls. At the phylum level, the Firmicutes to Bacteroidetes ratio was consistently decreased in GD patients (66.7%). Most GO patients also exhibited a similar disequilibrium in their gut and orbital adipose microflora. At the genus level, Prevotella (11 studies), genera within the Lactobacillaceae family (three studies), and Streptococcus (three studies) consistently showed an increase. Genera from the families Lachnospiraceae (nine studies), Ruminococcaceae (six studies), and Veillonellaceae (five studies), as well as the genus Bacteroides (three studies), were decreased. Conclusions: GD/GO-associated dysbiosis is characterized by reduced microbial richness and evenness and alterations in gut phyla balance (↓ Firmicutes, ↑ Bacteroidetes, ↑ Proteobacteria). Specific genera—including Lactobacillus, Prevotella, Bacteroides, and members of the Lachnospiraceae family—may plausibly act as contributors to the onset or progression of GD/GO by influencing the Th17/Treg balance, although their exact roles remain uncertain and largely hypothetical. Systematic review registration: PROSPERO identifier CRD42024512007. Full article

Background and Objectives: Post-thyroidectomy hypoparathyroidism (hypoPTH) is the most common complication of total thyroidectomy. Transient hypoPTH was defined as postoperative day 1 (POD1) intact parathyroid hormone (PTH) < 15 pg/mL and/or symptomatic hypocalcemia (<8.0 mg/dL), requiring supplementation, resolving within six months. We evaluated POD1 calcium, PTH, and their combination; identified preoperative predictors; and compared absolute with percent-change metrics. Materials and Methods: Participants comprised a retrospective single-center cohort of 380 consecutive adults undergoing total thyroidectomy between January 2023 and December 2025. Multivariable logistic regression identified preoperative predictors, and receiver operating characteristic (ROC) analysis evaluated POD1 biomarkers. Because both biomarkers are part of the outcome definition, a pre-specified sensitivity analysis re-evaluated POD1 PTH and ΔPTH against PTH-independent outcomes (POD1-calcium-defined hypocalcemia and permanent hypoPTH). Subgroups examined malignancy and central neck dissection (CND). Results: The cohort comprised 193 males (50.8%) and 187 females (49.2%), with a median age of 53 years (IQR 38–69). Indications were multinodular goiter (45.0%), differentiated thyroid cancer (37.9%), Graves’ disease (15.0%) and recurrent disease (2.1%). CND was performed in 9.5% of patients. Transient and permanent hypoPTH occurred in 132 (34.7%) and 11 (2.9%) patients. Thyroid gland weight was the sole independent preoperative predictor (OR 0.982, 95% CI 0.969–0.995, p = 0.008), with smaller glands conferring higher risk. Against the composite outcome, POD1 calcium and PTH yielded AUCs of 0.997 and 0.991 (combined 1.000), reflecting partial circularity. In the decoupled-outcome sensitivity analysis, POD1 PTH retained good-to-excellent discrimination for severe hypocalcemia (AUC 0.943) and permanent hypoPTH (AUC 0.976). Malignant cases showed a greater relative PTH decline than benign cases (−53.7% vs. −38.5%, p = 0.013) despite comparable absolute POD1 values, and CND did not increase risk. Conclusions: Combined POD1 calcium and PTH provided strong biochemical confirmation of transient hypoPTH, but the composite-outcome AUCs reflect internal definitional consistency rather than independent predictive performance; the decoupled-outcome AUCs (0.93–0.98) are the conservative benchmark. Thyroid gland weight was an inverse risk modifier with limited stand-alone utility. Multicenter prospective validation is required. Full article

Background: Increasing evidence suggests that COVID-19 can induce or exacerbate autoimmune disorders, including immune-mediated thyroid dysfunction. The most common autoimmune thyroid diseases are Graves’ disease and Hashimoto’s thyroiditis; the mechanisms by which viral infections like SARS-CoV-2 trigger these diseases are not fully understood. Objectives: This study aims to systematically review published clinical evidence on the presentation, laboratory characteristics, and outcomes of autoimmune thyroid diseases after COVID-19 infection. Methods: The review followed the PRISMA 2020 framework. Scopus, Web of Science, and PubMed were searched for English-language studies between January 2020 and December 2025 using the terms COVID-19, SARS-CoV-2, autoimmune thyroiditis, Graves’ disease, Hashimoto’s thyroiditis, and autoimmune thyroid disease. Results: In total, 46 studies (five cohort studies and 41 case reports/series) involving 3856 patients were analyzed. The findings indicate that a significant increase in TPOAb prevalence occurs post-COVID-19 infection (15.7% vs. 7.7% in controls). New-onset Graves’ disease (GD) post-COVID-19 presented with higher fT3/fT4 ratios and more aggressive thyrotoxicosis compared to non-viral cases. Rare but severe manifestations included thyrotoxic periodic paralysis, Hashimoto’s encephalopathy, and dilated cardiomyopathy. Conclusions: SARS-CoV-2 may act as a trigger for autoimmune thyroid diseases, particularly in moderate-to-severe infections; however, the strength of this association warrants further investigation with controlled prospective data. Standard therapy remains effective, but thyroid function monitoring is advisable during post-COVID-19 recovery. An interdisciplinary approach is essential for early diagnosis and management of systemic complications. Full article

Objectives: To validate claims-based algorithms for identifying thyroid eye disease (TED) cases and assess whether machine learning can improve case identification in a large, linked real-world dataset. Methods: Using a large, linked database from Komodo Health^® and Academy IRIS^® Registry, we evaluated six rule-based algorithms incorporating Graves’ disease (GD), eye symptoms and signs. The IRIS Registry’s curated data, based on confirmed TED diagnoses from medical notes, served as the reference standard. Additionally, we developed supervised machine learning models using demographic, diagnostic, procedural, and medication data. Feature selection was performed using recursive feature elimination to rank predictive codes and construct a simplified, interpretable model. Cross-validation was used to assess model performance and compare performance with the rule-based algorithms. Results: The rule-based algorithms demonstrated a trade-off between sensitivity and specificity, with some achieving high specificity but limited sensitivity. Algorithm 1 had the highest sensitivity (48.7%) but lower specificity (59.9%) and PPV (75.8%). Algorithms 2–5 demonstrated higher specificity (87.2–93.5%) but lower sensitivity (17.8–27.0%). Algorithm 6 improved sensitivity (33.4%) compared to Algorithms 2–5 while maintaining high specificity (86.8%) and a strong PPV (86.7%). Machine learning models demonstrated similar trade-offs. One model achieved improved specificity (77.2%) with sensitivity of 49.3%, outperforming Algorithm 1 in specificity while matching its sensitivity. Another model maximized specificity (91.7%) and PPV (89.8%) at a reduced sensitivity of 28.5%. These results highlight the flexibility of machine learning models in adjusting performance to address different research objectives. Conclusions: This study evaluated existing rule-based algorithms for identifying TED cases in claims data, revealing trade-offs between sensitivity and specificity. Machine learning models provide additional flexibility, allowing performance to be tailored to specific research use cases. While no single method consistently outperformed others across all metrics, both rule-based and machine learning approaches demonstrated value in improving TED case identification using real-world data sources. Full article

Graves’ orbitopathy (GO) is a representative extrathyroidal manifestation of autoimmune thyroid disease. Despite extensive research, the precise pathogenic mechanisms remain incompletely understood. Moreover, the lack of an ideal animal model has limited in vivo investigation, with most studies relying on in vitro systems using orbital fibroblasts. In this review, we discuss currently available mouse models of GO and recent advances in experimental modeling strategies, aiming to provide an integrated framework for future research. Full article

Thyroid hormones regulate a complex and interconnected network of metabolic signaling. Thyroid dysfunction is, at present, defined and monitored through circulating thyroid-stimulating hormone (TSH) and free thyroid hormones. However, biochemical normalization does not entirely indicate restoration of metabolic homeostasis. This discrepancy highlights a critical limitation of the current TSH-centric paradigm, which also fails to explain the heterogeneity in cardiometabolic outcomes observed among patients with similar biochemical profiles. Metabolomics, through the analysis of tissue-specific biofluids, could aid in capturing the complex metabolic perturbations that characterize this disease. In this review, we summarize metabolomic signatures typical of thyroid dysfunction, perform a critical evaluation of limitations and variability across studies, and explore the clinical and translational implications of metabolomics in thyroid pathology. In addition, five metabolic hubs influenced by thyroid hormone activity are summarized: (i) lipid and lipoprotein remodeling; (ii) mitochondrial energetics and redox balance; (iii) amino acid metabolism and protein turnover; (iv) gut–liver–thyroid axis and (v) biological impact of subclinical thyroid diseases. Taken together, these findings challenge the sufficiency of a diagnostic model based on TSH measurement and pose metabolomics as a promising tool to refine risk stratification, uncover subclinical vulnerability and guide patient-centered management of thyroid disease. Despite its promise, clinical adoption of metabolomics is hindered by a lack of standardization and complex data interpretation. To overcome these limitations, coupling metabolomics with genomics and transcriptomics may allow its translation into practical application. Full article