Immune checkpoint inhibitor (ICI)-induced thyroiditis is a common immune-related adverse event (irAE) linked to improved survival. Polygenic risk scores (PRSs) for autoimmune hypothyroidism predict thyroid irAEs in European-ancestry patients; performance in non-European populations is unclear. In the Veterans Affairs Million Veteran Program (2011-2023), we identified ICI-treated patients with germline genotyping and a chemotherapy-treated control cohort, excluding those with thyroid disease or prior thyroid-directed treatments. Harmonized ancestry and race (HARE) defined Non-Hispanic White (NHW) and Black (NHB) groups. Thyroid irAEs within one year were defined using laboratory criteria capturing both hyperthyroid and hypothyroid phases. We compared two PRSs: a published European-derived PRS, and an updated PRS selected across multiple GWAS sources and methods (including MVP multi-ancestry GWAS) to maximize discrimination in African-ancestry individuals in a held-out test set. HARE-stratified multivariable Cox models estimated time to thyroiditis; a 6-month landmark analysis assessed overall survival. The ICI cohort included 4,289 patients (3,473 NHW; 816 NHB). The baseline PRS was associated with thyroiditis in NHW (adjusted hazard ratio [aHR] per SD 1.33, 95% CI 1.19-1.50) but not NHB patients or controls. The updated PRS improved risk stratification in NHW (aHR 1.45, 1.28-1.63) and predicted thyroiditis in NHB patients (aHR 1.48, 1.11-1.98), but not in controls. Thyroiditis within 6 months was associated with improved survival, but neither PRS was. Germline polygenic liability to hypothyroidism predicts ICI-induced thyroiditis in NHW and NHB patients when PRSs are selected via ancestry-stratified validation. Careful exploration of the dataset-method space is critical for equitable PRS development.
The therapeutic landscape for the treatment of type 2 diabetes mellitus (T2DM) has greatly evolved with the introduction of glucagon-like peptide-1 receptor agonists (GLP-1 RAs); however, concerns regarding their potential association with thyroid cancer have emerged. The aim of this study is to analyze individual case safety reports (ICSRs) involving GLP-1 RAs, focusing on thyroid cancer-related adverse events (AEs) using the European pharmacovigilance database. ICSRs reporting GLP-1 RAs (semaglutide, liraglutide, exenatide, lixisenatide, dulaglutide) or the dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) agonist tirzepatide as suspected drugs were retrieved from the EudraVigilance (EV) database from 1st January 2022 to 26th September 2024. A disproportionality analysis was performed to compare the probability of reporting thyroid cancer-related AEs among these drugs using the reporting odds ratio (ROR) and its 95% confidence interval (95% CI). Considering the different therapeutic indications, a sensitivity analysis was also conducted. A total of 34,956 ICSRs were included in the analysis. The majority of AEs were experienced by adult and elderly female patients. The most reported system organ classes (SOCs) were: "gastrointestinal disorders", "general disorders and administration site conditions", and "injury, poisoning and procedural complications". Disproportionality analysis revealed that semaglutide had a lower probability of reporting thyroid cancer-related AEs than tirzepatide (ROR = 0.54, 95% CI 0.37-0.81, p < 0.05), whereas sensitivity analysis revealed no significant signals across stratified therapeutic groups. These findings should be interpreted with caution, given the inherent limitations of pharmacovigilance databases. Further studies are recommended to better assess the potential causal relationship between GLP-1 RAs and thyroid cancer.
To map real-world management of paediatric differentiated thyroid carcinoma (DTC) across Europe and identify targets for harmonization. Cross-sectional, web-based survey of centres providing paediatric DTC care. One consolidated response per centre was requested from a clinician overseeing paediatric DTC. The instrument covered centre profile/multidisciplinary tumour (MDT) board organization; staging and guideline use; risk stratification and dynamic response; diagnostics; surgery/lymph node management; radioactive iodine therapy (RAIT) policy and activity selection; and thyroid-stimulating hormone targets, follow-up, shared-care/transition. Analyses were descriptive at centre level. Forty-two centres from 18 countries participated in the survey. Response denominators varied by item. Among responding centres, ≈75% were university or academic hospitals, ≈70% used a paediatric age cut-off of ≤18 years, and ≈60% reported having a dedicated MDT board. Staging and guideline use were heterogeneous: centres most often reported mixed or centre-specific guidance, followed by the American Thyroid Association (ATA) 2015 guideline, national guidelines, and the European Thyroid Association (ETA) 2022 guideline. Dynamic response-to-therapy categories were commonly used. For unilateral presumed low-risk disease, hemithyroidectomy was the usual initial surgery in approximately two-thirds to three-quarters of centres, whereas total thyroidectomy was less common. For low-risk patients, RAIT policy were split between de-escalation and risk-adapted use. When administered, RAIT activity was determined using weight-based, dosimetric, or fixed empirical approaches. Country-level patterns suggested clustering around ETA-leaning, ATA-leaning, and national guideline frameworks. Across Europe, centres broadly endorse risk-adapted care but diverge at key decision nodes-extent of surgery, formal risk framework, and RAIT in low-risk disease-reflecting guidance plurality and organizational context. Leveraging existing infrastructures offers pragmatic avenues to reduce unwarranted variation while generating paediatric-specific evidence to refine recommendations.
BACKGROUND: Graves’ hyperthyroidism is caused by stimulatory autoantibodies. Its diagnosis and monitoring are commonly based on measurement of thyrotropin receptor antibodies (TRAb) with unspecific immunoassays, that also detect neutral and blocking antibodies. TRAb analyzed using the Siemens IMMULITE® 2000 TSI immunoassay (TRAb-IM), designed to target stimulatory immunoglobulins, represents a promising alternative. This study aimed to determine the clinical performance of TRAb-IM and the Thermo Fisher BRAHMS TRAK KRYPTOR immunoassay (TRAb-KR) in a real-world setting. METHODS: Over 3 months, TRAb-IM was analyzed in samples collected to measure TRAb-KR after referral for thyrotoxicosis or at the time of discontinuation of antithyroid drugs (n = 168). Data on thyroid hormones, TRAb-KR, and date of start/discontinuation of antithyroid drugs was collected. RESULTS: Agreement analysis for Graves’ disease diagnosis between the assays yielded a Gwet’s AC1 of 0.69 (95% confidence interval [CI] 0.51–0.86) for the samples collected after referral for thyrotoxicosis (n = 122). In this group, sensitivity (95% CI) for TRAb-IM and TRAb-KR was 97% (86–100) and 78% (62–90), respectively, in overt hyperthyroidism (n = 49), and 71% (42–92) and 43% (18–71), respectively, in subclinical hyperthyroidism (n = 46). Specificity was 100% (74–100) for both assays in overt hyperthyroidism, and 97% (84–100) and 100% (89–100), respectively, in subclinical hyperthyroidism. When TRAb-IM and TRAb-KR results were used as predictors for recurrence at the time of discontinuation of antithyroid drugs, the ROC AUC was 0.65 (95% CI 0.47–0.82; p = 0.07) and 0.57 (95% CI 0.41–0.73; p = 0.40), respectively. CONCLUSIONS: The TRAb-IM assay presented better clinical performance at both diagnosis of Graves’ disease and prediction of its recurrence compared to the TRAb-KR assay. Nonetheless, endocrinologists should be aware that both assays are weak in diagnostic of subclinical cases and in the prediction of recurrence, when used at the time of discontinuation of antithyroid drugs.
Obesity and thyroid disorders are highly prevalent conditions with complex, bidirectional interactions. Thyroid hormones, particularly triiodothyronine, regulate energy expenditure, thermogenesis, and lipid metabolism, while excess adiposity can modulate hypothalamic-pituitary-thyroid (HPT) axis activity. Individuals with obesity frequently exhibit elevated thyroid-stimulating hormone (TSH) levels in the absence of true thyroid disease, suggesting an adaptive rather than pathological response. The balance of current evidence suggests that non-autoimmune hyperthyrotropinemia predominates in severe and morbid obesity, whereas autoimmune hypothyroidism may be relatively more common in mild to moderate obesity. Obesity also induces structural changes in the thyroid, including increased volume, hypoechogenicity, and adipocyte infiltration, which may reverse with weight loss. Weight-reduction interventions-including dietary strategies, bariatric surgery, and pharmacotherapy-consistently reduce TSH with variable effects on free thyroid hormones. Emerging therapies, such as GLP-1 receptor agonists, may influence the HPT axis directly or indirectly through weight loss, though data remain limited. Understanding the interplay between obesity and thyroid function is important for the appropriate interpretation of thyroid function tests, differentiation of adaptive versus pathological changes, and optimization of treatment strategies in patients with excess adiposity.
Sphingosine-1-phosphate (S1P) is a versatile immunomodulatory lipid mediator that affects both immune and cardiovascular health. S1P has been linked to thyroid health, for example by affecting inflammatory reactions found in Graves' disease. In our study, we explored associations of S1P with thyroid markers obtained from laboratory tests (thyrotropin [TSH], free triiodothyronine [fT3], and free thyroxine [fT4]) and ultrasound examination. We quantified S1P by LC-MS/MS in participants from the population-based 'Study of Health in Pomerania' conducted in Northeast Germany. Serum levels of TSH, fT3 and fT4 were measured using chemiluminescent immunoassays. Thyroid volume, thyroid nodules, and echogenic patterns were assessed by ultrasonography. Cross-sectional associations between serum S1P and thyroid biomarkers were evaluated using multivariable linear regression models adjusted for confounding. The total study population consisted of 4,034 participants (51.6% women aged 20 to 84 years). A one µmol/L higher S1P level was associated with a 0.17 mIU/L lower TSH level (95% confidence interval [CI]: -0.32; -0.04) and a 0.52 pmol/L [0.42; 0.63] higher fT3 level. These associations persisted after excluding individuals with high or low serum TSH levels and those taking thyroid medication. S1P levels were not significantly associated with serum fT4 levels. Higher S1P levels were associated with a larger thyroid volume, the presence of thyroid nodules, and a hypoechogenic thyroid pattern. Circulating S1P is inversely associated with TSH and positively associated with fT3, suggesting a potential modulatory role of S1P in thyroid function.
Alterations in levels of 25-hydroxyvitamin D have been associated with the risk of thyroid disease. This study uses Mendelian randomization (MR) to infer the possible causal association of 25-hydroxyvitamin D with hypothyroidism. We performed two-sample MR using the summary statistics data from genome-wide association studies (GWAS) from populations with European ancestry to infer the causality of genetically controlled levels of 25-hydroxyvitamin D on the risk of hypothyroidism, Hashimoto's thyroiditis, and biochemical parameters of thyroid diseases. The inverse-variance-weighted (IVW) method was used as the primary method to calculate the combined effect of all SNPs. Other methods were adopted to evaluate the stability and reliability of the results. Comprehensive sensitivity analyses were conducted to ensure that none of the MR analysis's primary assumptions were violated. The results of the IVW analysis revealed a significant causal association between higher levels of 25-hydroxyvitamin D and lower risk of hypothyroidism (beta = -0.197, 95% CI [-0.301, -0.093]; SE = 0.053, Pbeta = 2.256 × 10-4) as well as increased levels of free T4 (beta = 0.204, 95% CI [0.094, 0.305]; SE = 0.056, Pbeta = 3.0506 × 10-4). On the other hand, no significant causality was determined for higher levels of 25-hydroxyvitamin D in association with Hashimoto's thyroiditis (beta = -0.047, 95% CI [-0.245, 0.151], p = 0.641) and TSH levels (IVW method: beta = -0.030, SE = 0.034, 95% CI [-0.097, 0.038]; P = 0.392). The results of this two-sample MR study provide evidence supporting the potential of 25-hydroxyvitamin D supplementation in reducing the risk of hypothyroidism.
In patients with Graves' disease, the 2016 American Thyroid Association guidelines and 2018 European Thyroid Association guidelines recommend the administration of Lugol's solution prior to surgery. The objective of this study was to evaluate whether preoperative administration of this solution in patients undergoing thyroidectomy for Graves' disease really improves surgical outcomes. Patients who underwent total thyroidectomy for Graves' disease, performed by high-volume surgeons, in six European centers, between 2019 and 2023, were retrospectively evaluated. Based on preoperative administration of Lugol's solution, two groups were identified: LS Group, including patients who received this solution, and NoLS Group, including those who did not receive it. Surgical outcomes were assessed after performing propensity score matching (1:1). According to the inclusion criteria, 1380 patients were enrolled: 622 in LS Group and 758 in NoLS Group. After propensity score matching, the study population consisted of 494 patients: 247 in LS Group and 247 in NoLS Group. Regarding complications, neck hematomas managed conservatively were significantly greater in NoLS Group (P = 0.016); while unilateral recurrent laryngeal nerve injury, overall postoperative hypoparathyroidism, and temporary hypoparathyroidism were significantly greater in LS Group (P = 0.026, P < 0.001, P < 0.001; respectively). The duration of surgery and postoperative hospital stay were significantly longer in LS Group (P < 0.001, P < 0.001; respectively). Based on our findings and those of other authors, we believe that the recommendations of existing guidelines should be revised.
Excess iodine from iodinated contrast media (ICM) can lead to thyroid dysfunction. Children, especially neonates and premature infants, may be more vulnerable due to their immature thyroid physiology. A systematic review was conducted using Embase, Medline (PubMed), Cochrane, Web of Science, and Scopus. Inclusion criteria were studies in children ≤18 years receiving ICM and that reported effects on thyroid function. Exclusion criteria included topical iodine exposure, prenatal administration, and irrelevant endpoints. Case reports, reviews and abstracts were also excluded. Most studies reported temporary thyroid function disturbances following ICM in children, particularly subclinical hypothyroidism. Overt hypothyroidism was rare and occurred mainly in neonates and high-risk groups. In certain studies, up to 25% of neonates showed TSH abnormalities, with a subset requiring levothyroxine treatment. Although even more rare, some studies also reported cases of thyrotoxicosis after ICM. ICM exposure can lead to thyroid dysfunction in children, especially in neonates, preterm infants, and those with risk factors. Risk-based screening and monitoring are recommended to allow timely detection and treatment.
Thyroid eye disease (TED), the most common extrathyroidal manifestation of Graves' disease, requires individualized management that integrates medical, radiotherapeutic, and surgical interventions. In this article, we present a society-endorsed, survey-informed Korean clinical practice framework, including consensus elements, for TED management. This framework integrates the 2022 American Thyroid Association/European Thyroid Association consensus, the 2021 European Group on Graves' Orbitopathy (EUGOGO) guideline, and contemporary Korean specialist practice patterns. A 2025 nationwide survey of 32 members of the Korean Society of Ophthalmic Plastic and Reconstructive Surgery characterized current Korean practice patterns in TED management. Korean oculoplastic surgeons showed high adherence to international recommendations, with 87.5% using both the clinical activity score and EUGOGO severity classification and 96.9% administering intravenous glucocorticoid therapy according to EUGOGO protocols. Distinctive features of Korean practice included frequent use of orbital radiotherapy (90.6%) and regional triamcinolone injections (81.2%) in selected clinical settings. For dysthyroid optic neuropathy, 59.4% of respondents reported using combined intravenous glucocorticoid therapy and orbital radiotherapy as the initial treatment approach. This framework stratifies treatment according to disease activity, severity, and predominant clinical phenotype to support context-adapted therapeutic decision-making. As emerging therapies such as teprotumumab become more accessible, this Korean clinical practice framework may provide practical guidance tailored to local clinical practice and healthcare-system constraints.
Sjögren's syndrome affects the skin, joints, lungs, kidneys, liver, and thyroid. This research was aimed to assess the association of Sjögren's syndrome with the thyroid carcinoma risk. The present study was used a systematic review and meta-analysis method. This study searched the databases ProQuest, PubMed, Web of Science, Cochrane, and the search engine Google Scholar until July 7, 2024. The level of significance was considered as P0.05, and all data analyses were done in STATA 14 software. A review of 11 studies revealed that Sjögren's syndrome increased the thyroid carcinoma risk in all patients (OR: 2.08, (95%CI: 1.47, 2.94)), in patients aged 40 to 49 years (OR: 1.43, (95%CI: 1.23, 1.67)), 50 to 59 years (OR: 4.65, (95%CI: 1.87, 11.58)), 60 to 69 years (OR: 1.34, (95%CI: 1.08, 1.66)) and in women ((OR:1.83, (95%CI: 1.35, 2.48). However, there was no significant association between Sjögren's syndrome and thyroid carcinoma risk in men ((OR: 1.49, (95%CI: 0.95, 2.34). Moreover, patients with Sjögren's syndrome who had a follow-up period of = 5 years ((OR: 1.68, (95%CI: 1.10, 2.54) and patients with a follow-up period of 5 years ((OR: 5.77, (95%CI: 1.97, 16.97) were at risk of thyroid cancer. Moreover, the thyroid carcinoma risk was in Europe ((OR: 3.26, (95%CI: 1.24, 8.56) and in Asia ((OR: 1.87, (95%CI: 1.27, 2.74). Primary Sjögren's syndrome also significantly increased the thyroid carcinoma risk ((OR: 2.37, (95%CI: 1.44, 3.90). Sjögren's syndrome increased the thyroid carcinoma risk, and female gender, fifth decade of life, European race, and involvement duration of more than 5 years were the exacerbating factors.
Hypocalcemia is the most common complication following thyroidectomy. Previous studies yielded inconsistent results on whether vitamin D3 prevents postoperative hypocalcemia and were conducted in non-European countries with different dietary habits and baseline vitamin D levels. Therefore, we explored the effect of preoperative vitamin D3 on post-thyroidectomy hypocalcemia in a Dutch cohort. Patients undergoing thyroidectomy between 2023 and 2025 received 100,000 IU vitamin D3 1 week before surgery ("vitamin D group") and were compared to a historical cohort (2019-2022) without vitamin D3 supplementation ("control group"). Outcomes included incidence of hypocalcemia (albumin-adjusted calcium < 2.00 mmol/L), need for postoperative supplementation, time until normocalcemia, length of hospital stay, and readmissions. Fifty patients received preoperative vitamin D3 and were compared to 154 controls (82.8% female, median age: 55 years [IQR: 43-66]). Vitamin D3 supplementation was associated with a reduced risk of biochemical hypocalcemia at all postoperative time points (OR 0.28, 95% CI: 0.11-0.68, p = 0.005), corresponding to a number needed to treat of five patients to prevent one case of hypocalcemia. As compared to controls, the need for postoperative supplementation and time to recover from hypocalcemia were lower in the vitamin D group (32.0% vs. 53.9%, p = 0.007; and 0 [0-2] vs. 3 [0-11] days, p = 0.002, respectively). No differences were observed in length of hospital stay or readmissions. Although larger randomized trials are needed to confirm these observations, preoperative vitamin D3 was associated with a significant reduction in post-thyroidectomy hypocalcemia in this observational cohort study. Given its low costs, this intervention may be considered for routine implementation in thyroidectomy patients.
Distinguishing preoperative criteria and postoperative histological features of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) from those of other thyroid tumors with follicular architecture and papillary nuclear features (non-NIFTP) is crucial to prevent overtreatment. In this study, we aim to identify the predictive factors of NIFTP. We conducted a retrospective study in which we collected cases of thyroid tumors with follicular architecture and papillary nuclear features diagnosed between 2012 and 2022. Clinicopathological characteristics, therapeutic modalities, and follow-up were compared between NIFTP and non-NIFTP tumors. Forty cases of NIFTP and 44 cases of non-NIFTP were identified. NIFTP accounted for 8.83% of all PTCs and 33.6% of all thyroid tumors with follicular architecture and papillary nuclear features. NIFTP was associated with younger age (p=0.005), isoechoic nodules on ultrasound (US) (p=0.004), regular contours (p=0.028), absence of microcalcifications (p=0.005), and predominance in European Thyroid Imaging Reporting and Data System 2 and 3 scores (p<0.001). They predominantly exhibited a nuclear score of 2 (p<0.001), focal nuclear abnormalities (p=0.015), and a thin capsule (p=0.004). No case of NIFTP showed distant or lymph node metastases. Multivariate analysis identified a nuclear score of 2, focal nuclear abnormalities, and a thin tumor capsule as independently associated with NIFTP. Our findings demonstrated the indolent nature of NIFTP and the utility of cervical US in raising preoperative suspicion for this entity. Because findings regarding the Bethesda classification were not available in our study, a prospective multicenter study with a larger sample size and a longer follow-up period is warranted to address this limitation.
The objective of this study was to examine the association between preconception body mass index (p-BMI) and maternal thyroid function longitudinally evaluated over pregnancy and to explore whether early-pregnancy thyroid parameters are associated with adverse obstetric outcomes. Using preconception BMI as a stratification variable, 1,107 pregnant women were classified as normal weight (NW), overweight (OW), or obese (OB). Thyroid function was assessed at ≤13 gestational weeks and at two subsequent time points. Thyrotropin (TSH) and free thyroxine (FT4) longitudinal trajectories were analyzed using generalized estimating equations, and the FT4-TSH relationship was evaluated by correlation analyses. As an exploratory analysis, logistic regression models were estimated to assess associations between first-trimester thyroid parameters and a composite adverse obstetric outcome (preterm delivery, labor dystocia, premature rupture of membranes, placental abruption, or abnormal amniotic fluid volume). At early pregnancy, OW and OB women exhibited lower FT4 and higher TSH concentrations than NW women. Across gestation, FT4 declined and TSH increased in all p-BMI categories, with persistently lower FT4 and higher TSH levels in women with higher p-BMI and no significant p-BMI × gestational period interaction. Low FT4 in the first trimester was independently associated with adverse obstetric outcomes (odds ratio (OR) = 2.04, 95% CI: 1.32-3.11, P = 0.001), whereas the association with elevated TSH was weaker (OR = 1.71, 95% CI: 1.04-2.77, P = 0.03). Higher p-BMI is associated with a persistently less favorable maternal thyroid hormone profile throughout pregnancy. Low FT4 concentrations during early pregnancy showed the strongest association with obstetric risk, supporting further investigation into early thyroid assessment in higher-risk populations.
Central congenital hypothyroidism (incidence ∼1:13,000) occurs in isolation (40% cases) or with additional pituitary hormone deficiencies. T4 ± TSH-based neonatal screening detects central congenital hypothyroidism within the first two weeks of life, permitting prompt treatment, but the UK TSH-based screening programme will not detect these cases. We delineated clinical characteristics, time-frame and pathway to diagnosis in clinically diagnosed individuals. Records were reviewed for 118 cases diagnosed from 1996 to 2022, in four tertiary centres. Median age at diagnosis was 68 days (range: 1-5,056). 96% had combined pituitary hormone deficiencies. Non-specific neonatal concerns (hypoglycaemia/jaundice/weight concerns, 83%) and significant neurodevelopmental defects (34%) occurred frequently. Compared with cases diagnosed late ( > 1 year, n = 42), early diagnosis ( ≤ 14 days n = 23) was associated with neonatal intensive care admission (78 vs 29%, P < 0.001) and ACTH deficiency (96 vs 40% P < 0.0001). Mean FT4 was moderately low at diagnosis (-2.7 ± 0.9 SDS), but initial thyroid function was within reported reference ranges in 31 cases. Treatment delays could be substantial, even following detection of subnormal FT4, especially in late-diagnosed cases (mean: 208 ± 486 days). UK central congenital hypothyroidism cases are diagnosed later than screening-detected cases, and isolated TSH deficiency may evade detection entirely. 'Sicker' neonates are diagnosed earlier, but late diagnosis frequently occurs despite neonatal/childhood morbidity attributable to combined pituitary hormone deficiencies. Challenges include non-specific neonatal signs, requirement for bespoke age-specific FT4 reference ranges, lack of biomarkers for alternative diagnoses and masking by concomitant GH deficiency. Our findings mandate further studies to assess practicalities, costs and justification for introducing UK-wide central congenital hypothyroidism screening.
Heavy metal mixtures (HMMs) containing lead (Pb), cadmium (Cd), and arsenic (As) induce oxidative stress and inflammation in thyroid and thymic tissues, disrupting endocrine and immune homeostasis. While Prosopis africana pod methanolic extract (PA) exhibits antioxidant properties, its protective mechanisms against multi-metal toxicity remain undefined. This study investigated PA's efficacy in mitigating HMM-induced organ injury in rats. Male Sprague-Dawley rats (n = 5/group) received environmentally relevant HMM [PbCl2 (20 mg/kg), CdCl2 (1.61 mg/kg), Na2AsO3 (10 mg/kg)] via drinking water with concurrent daily oral gavage of PA extract (500, 1000, or 1500 mg/kg) for 60 days. Tissue metal accumulation was quantified by atomic absorption spectrophotometry and oxidative stress markers spectrophotometrically. Inflammatory mediators (TNF-α), apoptotic markers (caspase-3), and pathway regulators (Nrf2, NF-κB) were measured by ELISA. Histopathological evaluation and multivariate analyses were performed. PA extract, rich in flavonoids and tannins, exhibited dose-dependent protective effects. Co-treatment significantly reduced Pb, Cd, and As accumulation in thyroid and thymus (up to 82% reduction in thyroid Cd at 1500 mg/kg compared to HMM controls, p < 0.05). Oxidative balance was restored, evidenced by a 79% decrease in malondialdehyde and recovery of antioxidant enzyme activities (SOD, CAT, GSH, GPx). PA normalized dysregulated Nrf2 expression and suppressed NF-κB activation, restoring functional antioxidant responses, resulting in marked attenuation of TNF-α (95% reduction) and caspase-3 (76% reduction). These biochemical improvements correlated with the prevention of HMM-induced organomegaly and preservation of normal histoarchitecture. Prosopis africana pod methanolic extract confers significant protection against HMM-induced thyroid and thymic injury through dual mechanisms: (i) substantial reduction of tissue metal bioaccumulation (up to 82% reduction in thyroid Cd), and (ii) restoration of functional Nrf2-mediated antioxidant responses while suppressing NF-κB-driven inflammation. Critically, PA normalized suggesting dysregulated compensatory Nrf2 elevation while enhancing antioxidant enzyme activities, demonstrating functional pathway restoration rather than mere suppression. These findings highlight PA's potential as a multi-targeted phytotherapeutic agent for mitigating heavy metal toxicity, warranting further mechanistic and translational studies.
We aimed to explore the association between thyroid indicators and pre-sarcopenic obesity, pre-sarcopenia, and visceral obesity in a community-based euthyroid cohort. A total of 1280 euthyroid residents (42.3% men) aged over 40 years were recruited in 2013-2014 and re-examined in 2015-2016. Thyroid indicators were analyzed. Visceral fat area (VFA) was quantified using magnetic resonance imaging and skeletal muscle mass was calculated by bioelectrical impedance analyzer. Pre-sarcopenic obesity was defined as the coexistence of pre-sarcopenia and visceral obesity. During a mean follow-up of 2.1 years, 127 (14.8%), 156 (21.3%), and 120 (20.1%) participants developed new-onset pre-sarcopenic obesity, pre-sarcopenia, and visceral obesity, respectively. Compared with those with the lowest tertile of baseline serum fT3 levels, participants with the highest tertile had an elevated risk of pre-sarcopenic obesity (risk ratio [RR] 1.82, 95% confidence interval [CI] 1.20-2.76) and pre-sarcopenia (RR 1.49, 95%CI 1.04-2.15). Moreover, per 1 standard deviation increase in serum fT3 levels over 2.1 years was positively associated with incident pre-sarcopenic obesity (RR 1.40, 95%CI 1.28-1.53) and pre-sarcopenia (RR 1.29, 95%CI 1.18-1.40), respectively. Elevated serum fT3 levels were associated with increased risks of pre-sarcopenic obesity and pre-sarcopenia in euthyroid Chinese participants.
Differentiated thyroid carcinoma (DTC) is traditionally treated with total thyroidectomy (TT); however, hemithyroidectomy (HT) has been increasingly used. Previous analyses on DTC recurrence rate with HT and TT have yielded inconsistent results; this study aimed to bridge this gap. Searches were conducted in PubMed/MEDLINE and Embase. Furthermore, references of previous systematic reviews were screened to extend the search until May 2025. Specific data on recurrence rate were independently extracted from the included studies by two observers and then pooled using a random-effect model. The primary endpoint was the risk difference (RD) in cancer recurrence rate between HT and TT. The secondary endpoints included recurrence prevalence (RP) for TT and HT and odds ratio (OR) comparing HT with TT. A total of 2,556 papers were initially identified, and 46 retrospective studies were included. The overall quality of the studies was satisfactory. In total, 98,604 patients were treated with TT (n = 75,531) or HT (n = 23,073). The proportion meta-analyses revealed a pooled RP of 5.8% in TT and 8.1% in HT. The HT group had a significantly higher probability of DTC recurrence than the TT group (OR = 1.56, 95% CI = 1.47-1.66, I 2 = 85%). The RD meta-analysis revealed that the recurrence rate was significantly higher in the HT group than in the TT group, by 3% (95% CI = 3-4, I 2 = 87%). The DTC recurrence rate following HT is significantly higher than that observed following TT. Thyroid specialists should consider this finding when tailoring initial treatment strategies.
BACKGROUND: Little is known about the relationship between thyroid diseases (TDs) and Idiopathic inflammatory myopathies (IIMs). This study aimed at evaluating the prevalence of TDs in a monocentric cohort of patients with IIMs, exploring possible correlations with clinical phenotype, organ involvement, comorbidities and quality of life (QoL). METHODS: We retrospectively analysed medical records of patients with IIM according to the EULAR/ACR 2017 criteria, collecting data about demography, IIM subset, disease duration, autoantibody profile, organ involvement and comorbidities. Besides, we registered the occurrence of Hashimoto Thyroiditis (HT), Multinodular goitre (MNG), Grave’s Disease (GD) and Thyroid papillary cancer (TPC). In addition, some different patient reported outcomes were administered, to collect data on QoL. RESULTS: A total of 191 patients were enrolled: 125 (65.4%) were female, with a mean age of 66.6 ± 13.5 years and a mean disease duration of 9.8 ± 7.4 years; 111 (58.1%) had dermatomyositis (DM), 50 (26.2%) polymyositis (PM), 11 (5.8%) clinically amyopathic DM or inclusion body myositis, 6 (3.1%) immune-mediated necrotizing myopathy and 2 (1%) juvenile DM. Ninety-nine patients (51.8%) had a TD; 53/191 (27.7%) had MNG, 42/191 (22%) had HT and 3/191 (1.6%) GD. One patient (0.5%) had a TPC. The presence of a TD was associated with oesophagus’ involvement and with a higher risk of osteoporosis and fragility fractures (p ≤ 0.01). Moreover, patients with TDs tended to accumulate a greater number of comorbidities (p < 0.001) and showed higher values of cumulative dose of glucocorticoids (p = 0.032). Finally, considering patients’ QoL, the presence of a TD was associated with lower values of the SF-36 bodily pain domain (p = 0.006). CONCLUSIONS: More than half of our IIMs patients had a TD, with a higher prevalence of both MNG and HT. Our results partially fill a lack of knowledge about the relationship between TDs and IIMs, stressing the opportunity of regularly screening patients for thyroid function. CLINICAL TRIAL NUMBER: Not applicable.
Rheumatoid arthritis (RA) has long been observed to co-occur with Hashimoto's thyroiditis, a condition characterized by the presence of thyroid peroxidase antibody (TPOAb); however, the specific contribution of TPOAb to RA pathogenesis remains unclear. Therefore, we aimed to investigate the association between TPOAb and RA. We performed a two-sample Mendelian randomization (MR) analysis using genome-wide association study (GWAS) summary data from East Asian and European population. This analysis was complemented by functional enrichment analyses and validation using cross-sectional data from 12,014 and 5,270 participants in the National Health and Nutrition Examination Survey (NHANES). In East Asian populations, both TPOAb concentration and TPOAb positivity were significantly associated with RA (OR = 1.447, P < 0.001; OR = 1.198, P < 0.001) and seropositive RA (OR = 1.349, P < 0.001; OR = 1.166, P = 0.002). In European populations, TPOAb concentration was significantly associated with RA, seropositive RA, and seronegative RA, while TPOAb positivity was significantly associated with RA and seropositive RA (all P < 0.05), but not seronegative RA. In the NHANES III dataset, TPOAb positivity remained significantly associated with RA and seropositive RA (OR = 1.358, P = 0.045; OR = 1.95, P = 0.046). Functional annotation further revealed enrichment of genes involved in immune regulation, immune cell differentiation, and activation. Collectively, these findings provide genetic and observational evidence supporting an association between TPOAb and RA. However, the potential role of TPOAb in rheumatoid arthritis risk prediction requires further investigation. Key Points • TPOAb were associated with rheumatoid arthritis. • The clinical value of TPOAb for rheumatoid arthritis risk prediction requires further validation.