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The physiological demands of pregnancy substantially alter iodine metabolism and thyroid function. This critical period heightens the requirement for iodine, making deficiency a significant risk factor for both maternal and fetal thyroid dysfunction. This study aimed to evaluate the iodine nutritional status of pregnant women in Hubei Province, explore the relationship between serum iodine concentration (SIC) and thyroid function, and determine the prevalence of thyroid disorders. The eligible participants underwent a face-to-face interview and completed questionnaire surveys to collect baseline information and dietary intake data. Serum thyroid hormones, thyroid antibodies, SIC, and urine iodine concentration (UIC) were measured. The 95% reference intervals of SIC were established and ROC analysis was applied to compare the predictive ability of SIC and UIC for thyroid dysfunction. Hubei Province, China. 1197 eligible pregnant women were included in this study. This study revealed a thyroid dysfunction prevalence of 28.40%, with hypothyroxinemia being the most prevalent thyroid function abnormality, accounting for 79.7% of all thyroid dysfunction cases. Significant differences in hypothyroxinemia prevalence were noted across pregnancy trimesters (P < 0.001), with the highest prevalence in the first trimester and the lowest in the third. In the first trimester, SIC was negatively correlated with TSH (r = -0.195, P < 0.001) and positively correlated with FT3 (r = 0.294, P < 0.001). Additionally, SIC demonstrated a positive correlation with FT4 in each trimester (all P < 0.001). Finally, the SIC reference intervals for pregnant women in the first, second, and third trimesters were 50.08∼118.61 µg/L, 59.16∼127.44 µg/L, and 53.61∼118.67 µg/L, respectively. SIC can serve as a reliable indicator for evaluating individual iodine nutritional status and predicting thyroid dysfunction.
Maternal hypothyroidism, characterized by insufficient thyroid hormone levels during pregnancy, is linked to adverse outcomes including preeclampsia, intrauterine growth restriction, and miscarriage. Beyond supporting fetal neurodevelopment, thyroid hormones are essential for maintaining maternal immune tolerance to the semi-allogeneic fetus. Regulatory T (Treg) cells, particularly those expressing Forkhead box P3 (FoxP3), are key mediators of this tolerance. Although reduced FoxP3+ Tregs have been associated with pregnancy complications, their role in maternal hypothyroidism remains unclear. Exosomes, important mediators of immune signaling, may also influence FoxP3+ Tregs, but their function in hypothyroid placentas is poorly understood. Placentas from hypothyroid and healthy pregnancies were analyzed. FoxP3 and the exosome marker CD63 were evaluated by immunohistochemistry and ELISA, with FoxP3 and the trophoblast marker CK7 also assessed by immunofluorescence. Histomorphological alterations were examined using H&E staining. Histomorphological analysis revealed pathological changes in hypothyroid placentas. A significant reduction in FoxP3+ cells was detected in hypothyroid placentas compared to controls, while CD63 expression showed no difference between groups. Immunofluorescence confirmed FoxP3 expression in trophoblasts. This study is the first to demonstrate an association between maternal hypothyroidism and FoxP3 expression and suggests that a reduction in FoxP3+ cells may contribute to impaired feto-maternal immune tolerance. The detection of FoxP3 in trophoblasts provides novel insight into their potential immunomodulatory role. These findings suggest that FoxP3 may act as a mediator in the pathophysiology of maternal hypothyroidism and highlight the need for further mechanistic and clinical studies.
Systemic lupus erythematosus (SLE), an autoimmune disorder, is linked to a heightened risk of multiple malignancies, including thyroid cancer. Thyroid cancer is the most prevalent malignancy of the endocrine system, and its autoimmune-related pathological features render it an optimal subject for investigating the mechanisms of their comorbidity. The molecular mechanisms underlying this comorbidity are still ambiguous. The accurate diagnosis and treatment of thyroid cancer urgently necessitate innovative molecular targets that extend beyond conventional pathological characteristics. This study seeks to employ integrated bioinformatics approaches to elucidate potential shared molecular mechanisms and immunological features between thyroid cancer and systemic lupus erythematosus (SLE), aiming to enhance understanding of their comorbidity and identify novel intervention targets. This study initially acquired gene expression data for TC and SLE from the GEO database and subsequently screened and identified differentially expressed genes (DEGs) shared by both diseases. Subsequently, we conducted Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome functional enrichment analyses on these 46 shared differentially expressed genes (DEGs) and further assessed the activation status of pertinent pathways using Gene Set Enrichment Analysis (GSEA). Subsequently, we employed CIBERSORTx to examine immune infiltration patterns and developed protein-protein interaction networks utilising the STRING database. We identified hub genes utilising the MCODE and cytoHubba plugins and visualised the findings with Cytoscape software. We additionally assessed the diagnostic efficacy of these core hub genes in an independent dataset utilising ROC curves and investigated their prognostic relevance in thyroid cancer through Kaplan-Meier survival analysis and multivariate Cox proportional hazards regression. Ultimately, we employed the Network Analyst platform to forecast transcription factor-gene and miRNA-gene regulatory networks and identified potential targeted therapeutic compounds utilising the DSigDB database. This study identified 46 differentially expressed genes (DEGs) commonly linked to thyroid cancer and systemic lupus erythematosus (SLE), which were significantly enriched in signalling pathways associated with immune-inflammatory activation, type I interferon responses, and complement pathway activation. Moreover, GSEA findings validated that immune-inflammatory and autoimmune-related pathways are markedly activated in both conditions. Twelve hub genes were discerned through protein-protein interaction networks. Analysis of immune infiltration indicated that thyroid cancer and systemic lupus erythematosus exhibit a shared characteristic of innate immune dysregulation, marked by the infiltration of myeloid cells (neutrophils, M0/M2 macrophages). Receiver operating characteristic (ROC) curve analysis identified six significant core hub genes with substantial diagnostic value: C1QB, LCN2, C1QC, LTF, VSIG4, and C3AR1. Univariate survival analysis indicated that elevated expression of C1QC and C3AR1 significantly enhances overall survival in thyroid cancer patients; however, multivariate COX regression analysis revealed that their independent prognostic significance necessitates further validation. This study predicted the interaction networks of transcription factors and miRNAs regulating key genes, with LCN2 demonstrating the highest connectivity to miRNAs, and identified candidate therapeutic compounds linked to it. This study employed bioinformatics analysis to identify critical shared hub genes and molecular pathways connecting thyroid cancer and systemic lupus erythematosus, offering novel insights into their shared pathogenesis and the advancement of targeted biomarkers and therapeutic strategies.
Hydroxychloroquine (HCQ) is a commonly used immunomodulatory drug in various autoimmune diseases; however, its role in autoimmune thyroid diseases (AITDs) remains unclear. This study aimed to evaluate the potential effects of HCQ in autoimmune thyroiditis using both naïve and experimental autoimmune thyroiditis (EAT) mouse models. Mice were administered HCQ via drinking water. Plasma levels of free thyroxine (FT4), anti-thyroglobulin antibody (ATA), B-cell activating factor (BAFF), and interferon-α (IFN-α), along with thyroid histopathology, were assessed. Thyroid tissues were subjected to next-generation sequencing (NGS), followed by over-representation analysis (ORA) and gene set enrichment analysis (GSEA) for functional enrichment evaluation. In EAT mice, HCQ treatment did not significantly affect FT4 or ATA levels, nor did it alter thyroid histological features. However, HCQ reduced human thyroglobulin stimulated splenocyte metabolic activity and plasma BAFF levels, indicating a systemic immunomodulatory effect. NGS of thyroid tissues revealed widespread upregulation of immune and inflammatory genes in EAT mice, which were partially attenuated by HCQ. GSEA also confirmed downregulation of immune-related pathways, including IL-6-JAK-STAT3 signaling and allograft rejection. No significant changes were observed in naïve mice treated with HCQ. In the context of autoimmune thyroiditis, HCQ showed preliminary immunomodulatory effects on certain immunological markers without recovering histological damage in the short term. Further long-term and mechanistic studies are warranted to clarify HCQ's therapeutic potential in autoimmune thyroiditis.
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.
During pregnancy, extensive hormonal and metabolic changes can occur. Gestational diabetes can cause maternal and neonatal complications. Follow-ups have shown that women who first develop metabolic diseases during pregnancy have an increased risk of developing other metabolic diseases, including hypothyroidism. There are contradictory results. The aim of this study is to provide an overview of the relationship between gestational diabetes and gestational thyroid dysfunctions. This study is a retrospective case-control study conducted in 2025 on 353 pregnant women in Iran; 176 were included in the case group (women with gestational diabetes) and 177 in the control group (women without gestational diabetes). The diagnosis of hypothyroidism was assessed in both groups. Descriptive statistics, chi-square test, t-test, and unconditional logistic regression were used to analyze the data. Gestational diabetes was associated with a significant increase in the risk of hypothyroidism (approximately 2.8-fold) (p = 0.03). A history of other diseases was also associated with a significantly increased risk of developing hypothyroidism (p = 0.001). In contrast, the risk of hypothyroidism was not significantly associated with age at first pregnancy (p = 0.10), number of pregnancies (p = 0.11), or breastfeeding (p = 0.35). Gestational diabetes and a history of other diseases significantly increased hypothyroidism risk, while age at first pregnancy, number of pregnancies, and breastfeeding showed no significant associations. Based on these findings, regular thyroid screening is suggested for pregnant women with gestational diabetes or other medical conditions, regardless of reproductive factors.
The thyroid gland is a highly vascularized organ in vertebrates. However, the information on the vascular pattern of this gland in pigs remains limited. This study elucidates the morphoanatomy and arterial supply of the gland in three breeds: Landrace (L), Large White (W), and Crossbreed (LWD). Two hundred twelve pigs were used and dissected to observe the arteries supplying blood to the gland. As a result, the gland was classified into three types based on its appearance: pear-shaped, butterfly-shaped, or partially separated. Moreover, the arteries supplying the gland were observed and then compared among breeds. The arterial supply of the thyroid gland on the cranial side consisted of branches from the cranial laryngeal artery, cranial thyroid artery, superficial cervical artery, and common carotid artery. Otherwise, the caudal side was supplied by the caudal thyroid artery, superficial cervical artery, bicarotid trunk, internal thoracic artery, and external thoracic artery. Furthermore, significant differences were identified between L and LWD, as well as between W and LWD, in the pattern of arterial origin on the cranial right side of the thyroid gland. Similarly, on the left side, significant differences were observed not only between L and W but also between W and LWD. On the caudal side, significant differences were found between L and W, as well as between W and LWD. These anatomical variations provide important insights for research and clinical applications involving the thyroid gland in pigs.
Continuous increases in the incidence of thyroid cancer emphasize the requirement for effective management policies. This study estimated the cost of a bundle reimbursement strategy for thyroid oncological treatment and compared it with a real-world cohort of patients. This retrospective single-center microcosting study was conducted in 2 steps: (i) thyroid oncological surgery bundle design and (ii) real-world cost variability between the estimated bundle and a cohort of patients. The bundle was designed based on clinical guidelines and the center's thyroid oncological surgical experience, represented by clinical registry data on 8381 cases. Time-driven activity-based costing (TDABC) was applied to estimate the bundle's cost, using data from a real-world cohort of 29 patients. The estimated and measured cost data were compared descriptively, and cost variability was analyzed using linear multiple regression. The thyroid cancer bundle covered care from preparation for surgery through postsurgical monitoring, including standard medications, exams, and involvement of health professionals. The estimated cost for the thyroid bundle was R$20,288 (US$3757), with the surgery accounting for 90% of the costs. The mean bundle cost based on the real-world cohort of patients was R$19,448 (SD 6690), with 33% of costs justified on hospital facilities. Patient' age and length of hospital stay were identified as cost drivers. This study is unique in evaluating the economic impact of adopting a bundle reimbursement strategy for one thyroid cancer treatment. Applying TDABC demonstrated the value of accurate costing for evaluating pricing and increasing the chances of achieving sustainability through an innovative care and payment strategy.
Thyroid cancer comprises biologically diverse entities ranging from largely indolent differentiated thyroid cancer (DTC) to aggressive poorly differentiated/anaplastic thyroid cancer and medullary thyroid cancer, generating a need for minimally invasive biomarkers that can be repeatedly sampled. This review summarizes recent advances in liquid biopsy for thyroid cancer, focusing on analytes and technologies spanning circulating tumor DNA (ctDNA)/cell-free DNA, circulating microRNAs (miRNAs), extracellular vesicles (EVs), and circulating tumor cells (CTCs). For ctDNA, we contrast qPCR/ddPCR and next-generation sequencing, tumor-informed versus tumor-agnostic strategies, the impact of low tumor fraction in DTC, clonal hematopoiesis confounding, and emerging methylation-based multi-cancer detection paradigms. For miRNAs, we highlight that bulk serum/plasma and EV-enriched compartments are not interchangeable and that regulated EV loading supports fraction-resolved biomarker development. We review recent translational EV-miRNA studies, including externally validated classifiers for metastatic disease and follicular-patterned/indeterminate nodules, and summarize the evolution of CTC research from enumeration to preoperative risk stratification and postoperative or radioiodine-related kinetics. We conclude with an indications-first framework that pairs analyte choice with clinical intent (preoperative diagnosis, initial risk stratification, response to treatment and minimal residual disease and identification of actionable alterations and resistance mechanisms) and prioritizes standardized workflows and prospective multicenter validation. Multi-analyte integration, epigenetic/fragmentomic cfDNA signals, and higher-resolution EV analytics are likely to accelerate clinical adoption, particularly in advanced thyroid cancer where circulating signal and therapeutic actionability are highest.
Radioactive iodine (RAI) is a crucial treatment for refractory pediatric and adolescent Graves' disease (GD) cases characterized by poor response to antithyroid drug (ATD), recurrence, adverse effects, or excessive thyroid enlargement. Compared to adults, pediatric and adolescent patients currently lack effective efficacy prediction models tailored to this specific population. Furthermore, the applicability of existing adult dose calculation standards to children remains controversial. This study aims to develop a predictive model and explore the cutoff values of key variables influencing treatment efficacy, thereby providing a new adjunctive tool for the clinical management of pediatric and adolescent GD patients. A total of 95 children and adolescents with GD who received RAI therapy at the Department of Nuclear Medicine, the Second Affiliated Hospital of Nanchang University, between January 2020 and May 2025 were initially screened. Following the exclusion of 13 patients who had undergone prior thyroid surgery, received non-initial RAI treatment, or lacked regular follow-up, 83 patients (aged 9-19 years; 58 females) were finally enrolled. Based on thyroid function status 6 months post-treatment, patients were categorized into the cured group (Clinical Cure and Hypothyroidism) and the uncured group (Ineffective and Partial Improvement). Univariate analysis and LASSO regression were employed for preliminary variable screening to identify predictive indicators. A multivariate logistic regression model was subsequently constructed based on these selected variables. Model performance was evaluated using the area under the curve (AUC), calibration curves, and decision curve analysis (DCA), with internal validation performed via Bootstrap (2000 resamplings). The optimal cutoff values were determined using the Youden index. The proposed dose per gram of thyroid tissue was a protective factor (OR = 1.048, 95% CI (1.01-1.09), P = 0.018); Thyroid weight (OR = 0.956, 95% CI (0.924-0.983), P = 0.004) and TRAb (OR = 0.914, 95% CI (0.861-0.963), P = 0.001) were risk factors. The model achieved an AUC of 0.833 on the original dataset, and an adjusted AUC of 0.810, After model establishment, further analysis of key variables revealed significantly reduced cure rates in patients with thyroid weight > 55.52 g, TRAb > 13.8 IU/L, and the proposed dose per gram of thyroid tissue < 97.5 µCi/g (3.61 MBq/g). A model incorporating the proposed dose per gram of thyroid tissue, TRAb, and thyroid weight effectively predicts treatment efficacy. For high-risk patients (thyroid weight > 55.52 g, TRAb > 13.8 IU/L), increasing the proposed dose (≥ 97.5 µCi/g or 3.61 MBq/g) is recommended to enhance treatment outcomes.
Thyroid cancer (TC), the most common endocrine malignancy, is closely linked to aging. In this study, we estimated DNA methylation (DNAm) age in TC tissues versus adjacent non-cancerous thyroid tissues using TCGA and GSE97466 datasets. We employed multi-tissue DNAm age estimators, specifically Horvath's clock and the Bayesian Neural Network (BNN) clock, to quantify epigenetic aging in TC and adjacent normal tissues from the TCGA and GSE97466 cohorts. We further integrated genomic, transcriptomic, and mutational analyses, including assessments of senescence-associated secretory phenotype (SASP), immune cell infiltration, and thyroid differentiation, to elucidate the associations between DNAm age acceleration and various cancer-related features. Our results revealed marked DNAm age acceleration in TC tissues relative to controls, with both models yielding significantly higher DNAm age estimates in tumors. Although DNAm age correlated strongly with chronological age in control tissues (R ≈ 0.94), this association was notably diminished in TC tissues (R ≈ 0.62). Moreover, TC tissues with accelerated DNAm age exhibited higher telomerase-associated gene expression score, heightened SASP signaling, and distinct immune profiles characterized by elevated M2 macrophages and reduced activated NK cells. Genomic analysis further showed a higher prevalence of BRAF mutations and lower thyroid differentiation scores (TDS) in the accelerated subgroup. No significant associations were detected between DNAm age and clinicopathological parameters or overall survival. Our findings provide valuable insights into the complex interplay between epigenetic regulation, immune dysfunction, and genomic instability in thyroid cancer, highlighting promising avenues for future research and therapeutic intervention.
Background: Nuclear medicine healthcare professionals (NMHP) sustain chronic occupational exposure to iodine-131 (I-131), conferring an elevated risk of radiation-induced solid thyroid cancer. Established radiobiological prediction tools derive risk coefficients from atomic bomb survivor data but are not configured for rapid individualized risk assessment in occupational exposure settings. This study examined whether machine learning algorithms can serve as high-precision computational surrogates for excess relative risk estimation in NMHP. Aim: The study aimed to (i) develop and validate three machine learning algorithms for predicting the excess relative risk per unit absorbed dose for radiation-induced solid thyroid cancer (ERR/Gy.RST), (ii) characterize relationships between dosimetric and demographic features and predicted risk, and (iii) identify the optimal algorithm for deployment in occupational health surveillance. Methods: A dataset of 4657 observations was constructed from Life Span Study-derived ERR/Gy parameters, adapted to occupational low-dose conditions, using a dose-and-dose-rate effectiveness factor of 2.0, per ICRP Publication 103. Five features (gender, age at exposure, current age, distance from the I-131 source, and cumulative absorbed dose in the thyroid) were used to train a decision tree regressor (dtcr), a random forest regressor (rfr), and a multilayer perceptron (MLP) neural network algorithm. Results: Cumulative absorbed dose in the thyroid correlated positively with ERR/Gy.RST (r = 0.63, p < 0.01), while radiation source distance demonstrated a strong inverse association (r = -0.38, p < 0.01). The MLP algorithm achieved R2 score = 0.999, MSE = 0.002, and MAE = 0.010, substantially outperforming the rfr (R2 score = 0.700, MSE = 0.410, MAE = 0.295) and the dtcr (R2 score = 0.510, MSE = 0.654, MAE = 0.289). Conclusions: The MLP algorithm provides a high-fidelity surrogate for established ERR/Gy.RST projection tools in the NMHP context, enabling computationally efficient, feature-integrated occupational radiation-induced thyroid cancer risk quantification. These findings suggest that machine learning-based surrogate modeling is a practical, scalable complement for occupational health practitioners and radiation protection officers to support individualized surveillance of radiation-induced thyroid cancer risk in nuclear medicine departments.
Background/Objectives: The present study estimated the potential therapeutic effects of Borassus flabellifer immature endosperm extract (BFE) on the metabolic disorders of diabetes and hypothyroidism using a mixed research design. Methods: Characterization of phytochemicals via GC-MS demonstrated a highly abundant list of bioactive compounds, and it encompassed phenolic derivatives, methylxanthines, fatty acids, and inositol-related compounds. Molecular docking indicated that the major phytoconstituents showed positive binding affinities to the most vital metabolism and endocrine receptors, namely, TRβ1, PPARγ, and AMP-activated protein kinase (AMPK). Notably, both compounds C1 and C2 were highly affined towards TRβ1 (-7.8 and -7.6 kcal/mol), which is attributed to interactions in the active site through hydrogen bonding and hydrophobic responses, which means that the identified compounds were found to have good predicted interactions with some metabolic- and thyroid-associated targets and could be used to form preliminary hypotheses for further mechanistic studies. The in vivo data showed that the disease-induced groups were marked by hyperglycemia, imbalance in thyroid hormones, and dyslipidemia, as well as liver, kidney, and heart dysfunction. BFE caused significant decreases in these changes, which were also observed through improvements in fasting blood glucose, T3, T4, and TSH; partial restoration of lipid profiles; and dampening of liver and kidney injury signalers. The cardiac risk indices were also reduced significantly after BFE administration. Positive changes in body weight gain, feed ratio, and metabolic ratio further reflected better physiological stability. Results: These findings were corroborated by histopathological analysis, which showed that the tissue architecture of the pancreas, liver, kidney, and heart had significantly recovered in the study. BFE still showed constant therapeutic activity even though the magnitude of response was attenuated when combined disease conditions were used. Conclusions: Comprehensively, the results indicate that BFE potentially plays a role in the amelioration of metabolic and endocrine abnormalities of diabetic and hypothyroid conditions. These observations should be regarded as hypothesis-generating, as further mechanistic and translational studies are needed to substantiate their biological relevance.
LncRNAs emerge as critical regulators of gene expression and epigenetic modulation in human cancer. However, the biological and clinical significance of the lncRNA GAS8-AS1 in differentiated thyroid cancers (DTCs) remains poorly understood. GAS8-AS1 expression in normal tissues was evaluated using LncExpDB. Quantitative RT-PCR was performed on 21 DTCs with matched adjacent normal tissues. RNA-seq data from TCGA (507 DTCs) were analyzed to assess GAS8-AS1 expression and clinicopathological associations. Independent validation was conducted using ENCORI (510 thyroid cancer, 58 normal) and TNMplot datasets. Expression profiles of GAS8-AS1-associated genes were analyzed in TCGA and were corroborated with ENCORI dataset. Co-expression analyses were performed to identify regulatory relationships. Functional characterization was conducted using siRNA-mediated knockdown of GAS8-AS1 in HEK293T and BCPAP cells, and overexpression studies in papillary thyroid cancer cell lines (K1 and BCPAP). Cell proliferation, migration, and invasion assays were performed. Pathway enrichment analyses were used to identify GAS8-AS1-mediated biological processes. GAS8-AS1 expression was significantly downregulated in DTCs compared with matched normal tissues (p < 0.0001). TCGA analysis confirmed lower GAS8-AS1 expression, which was markedly associated with early-stage disease (p = 0.03) and lymph node metastasis (p = 0.03). GAS8-AS1 downregulation was remarkably consistent in thyroid cancer (ENCORI, p = 0.004). A dramatic downregulation of GAS8-AS1 was also observed across pan-cancer, including thyroid cancer (TNMplot, p = 2.01 × 10-128). Expression analysis of GAS8-AS1-associated genes revealed frequent deregulation in DTCs (24%), including downregulation of ATF2, ATG5, ATG7, and BECN1, and upregulation of NEAT1 and UCA1. Co-expression analysis revealed that GAS8-AS1 and ATG5 expression levels were positively correlated with ATF2, whereas NEAT1 showed a negative association, suggesting ATF2-dependent transcriptional regulation of GAS8-AS1, ATG5, and NEAT1. Functional characterizations demonstrated that GAS8-AS1 knockdown significantly increased proliferation, migration, and invasion, whereas GAS8-AS1 overexpression markedly suppressed tumor cell proliferation. Pathway enrichment analyses implicated GAS8-AS1-related genes in autophagy, apoptosis, proliferation, invasion, and metastasis. These findings demonstrate that GAS8-AS1 may function as a tumor suppressor in DTCs, with its downregulation associated with disease progression and metastasis. The consistent loss of GAS8-AS1 expression and its functional impact on tumor progression suggest that it may serve as a valuable diagnostic and prognostic biomarker in DTCs.
This study aimed to clarify the association between iodine supplementation and thyroid function indices, as well as secondary outcomes including thyroglobulin (Tg) and thyroid volume (TV), in iodine-deficient pregnant women, accounting for different supplementation regimens and trimesters. Chinese and English literature on iodine supplementation in iodine-deficient pregnant women and its associations with thyroid function indices, Tg, and TV was retrieved from PubMed, Medline, Embase, CNKI, WanFang, and WeiPu databases. Effect sizes were estimated using fixed- and random-effects models, reported as standardized mean difference (SMD), odds ratio (OR), and 95% confidence intervals (CIs). Iodine supplementation was associated with reduced serum TSH and Tg levels in iodine-deficient pregnant women (TSH: SMD = -0.14, 95% CI: -0.23, -0.05; Pz = 0.002; Tg: SMD = -0.22, 95% CI: -0.32, -0.13; Pz < 0.001). Subgroup analyses showed significant TSH reductions in Asian populations, third trimester, daily supplementation, 200-300 μg/d doses, and potassium iodide use (Pz < 0.05). Tg was significantly reduced across all regions, iodine supplementation dosages and methods, second/third trimesters, and daily supplementation subgroups (Pz < 0.05). TV was significantly increased in the Europe subgroup and the until postpartum supplementation subgroup (Pz < 0.01). Egger's test suggested publication bias for TV, but results remained robust after trim-and-fill adjustment. Standardized iodine supplementation notably reduces serum TSH and Tg in iodine-deficient pregnant women, relieving gestational thyroid dysfunction and optimizing maternal thyroid health. Greater TSH improvements are observed in Asian populations, the third trimester, and those taking 200-300 μg potassium iodide daily. https://www.crd.york.ac.uk/PROSPERO/view/CRD420261323017, identifier: CRD420261323017.
Thyroid hormone alterations are common in critical illness and may reflect disease severity. Their prognostic significance in infarct-related cardiogenic shock remains incompletely defined. In this prospective cohort study from a cardiogenic shock registry, 41 patients with acute myocardial infarction complicated by cardiogenic shock underwent serial measurements of thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) at baseline and 24, 48, 72, and 96 h after percutaneous coronary intervention. Associations between hormone trajectories and in-hospital mortality were assessed using longitudinal and small-sample-robust methods. Thyroid trajectories diverged by outcome. Survivors maintained higher TSH concentrations over time, whereas non-survivors showed progressive suppression. fT3 declined in both groups early after presentation, with a steeper overall decline in non-survivors and outcome separation becoming most apparent later in the observation period. Lower fT3 was associated with greater illness severity and higher mortality risk. fT4 decreased over time in both groups without consistent between-group differences. In conclusion, dynamic alterations in thyroid hormone levels, particularly reductions in fT3, were associated with greater illness severity and adverse outcomes in cardiogenic shock. Serial thyroid function assessment may improve risk stratification in acute cardiovascular critical illness and warrants further evaluation in larger prospective studies.
This research aims to develop an alternative sarcopenia screening score based on thyroid hormone function parameters, intended for screening and validating the probability of having sarcopenia among middle-aged and elderly participants with normal thyroid function tests in China. This multicenter, cross-sectional study assessed the prevalence of sarcopenia among 3,858 thyroid-healthy Chinese adults across hospitals in western China hospitals. Participants were randomized to exploratory and validation cohorts. After applying Lasso to select variables, multivariate logistic regression analysis was conducted. We developed a novel sarcopenia screening score from exploratory data, subsequently validating it internally across both cohorts. The new sarcopenia screening score comprises five variables: age, body mass index (BMI), calf circumference (CC), aspartate aminotransferase/alanine aminotransferase ratio (AST/ALT), and free T4 (FT4), with a scoring range of 0-14. The area under the receiver operating characteristic (ROC) curve for screening for sarcopenia was 0.845 (95% CI: 0.831-0.859) in the exploratory group and 0.854 (95% CI: 0.831-0.874) in the validation group. At the optimal cutoff of 3, the sensitivity and specificity were 78.3% and 75.1%, respectively, in the exploratory cohort; in the validation cohort, with a cutoff of 4, sensitivity and specificity were 68.4% and 87.0%. The Brier score was 0.092 in the exploratory cohort and 0.068 in the validation cohort, confirming satisfactory calibration. The newly developed sarcopenia screening score shows promise as a practical tool for identifying sarcopenia in middle-aged and elderly participants with normal thyroid function tests in China.
The thyroid, ultimobranchial, and adrenal glands are major endocrine organs in birds, essential for regulating various physiological functions. This study presents a comprehensive morphological and ultrastructural investigation of these three glands in adult male Egyptian turkeys using light microscopy, and transmission electron microscopy (TEM). The thyroid and ultimobranchial glands are in the thoracic cavity near the trachea, while the adrenal glands are positioned adjacent to the caudal vena cava and cranial poles of the kidneys. Histologically, the thyroid follicles are lined by simple cuboidal to columnar epithelium. The ultimobranchial gland appears as a single-lobed structure encased in a thick capsule and composed of C-cell follicles and cords. These C cells exhibit light and dark variants, with ultrastructural evidence of secretory granules, abundant vacuoles, and active rough endoplasmic reticulum. The adrenal gland is encapsulated by a thick layer of connective tissue. Its parenchyma showed intermingled interrenal and chromaffin cells, with the former arranged in multilayered follicles. Chromaffin cells formed large clusters and are distinguished into epinephrine and norepinephrine types by ultrastructure and Grimelius silver staining. These findings contribute valuable insights into the comparative avian endocrinology and structural adaptations of the turkey's endocrine organs.
The relationship between liver-related metabolic markers and thyroid nodules (TNs) has attracted increasing interest. However, whether the Fibrosis-4 (FIB-4) index is independently associated with TN prevalence in women, particularly after accounting for the age embedded in the score, remains unclear. We investigated the association between FIB-4 and prevalent TNs in a female health-check cohort and assessed its robustness in age-stratified and age-adjusted analyses. We conducted a cross-sectional analysis of 695 women from a health examination cohort at The Second Affiliated Hospital of Anhui Medical University. TNs were defined as ultrasound-detected thyroid nodules. Multivariable logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) for prevalent TNs according to standardized FIB-4 levels. Prespecified age-stratified analyses were performed for women aged ≤ 60 years and > 60 years. Within each age stratum, an additional model adjusted for continuous age. Age-adjusted within-stratum results were considered the main basis for interpretation. In the full female cohort, the association between FIB-4 and prevalent TNs was attenuated after additional adjustment for continuous age (OR 1.104, 95% CI 0.822-1.484; P = 0.511). In age-adjusted within-stratum analyses, FIB-4 was not significantly associated with prevalent TNs in either women aged ≤ 60 years (OR 1.211, 95% CI 0.837-1.751; P = 0.310) or women aged > 60 years (OR 0.567, 95% CI 0.289-1.113; P = 0.099). The corresponding base model estimates before additional continuous-age adjustment were OR 1.564 (95% CI 1.086-2.253; P = 0.016) and OR 0.576 (95% CI 0.278-1.193; P = 0.138), respectively. The interaction between FIB-4 and age group was not statistically significant (P for interaction = 0.239). After additional adjustment for continuous age within age strata, the association between FIB-4 and prevalent thyroid nodules in women was attenuated and no longer statistically significant. These findings suggest that the apparent relationship between FIB-4 and TN prevalence in this health-check population may be substantially influenced by age handling and should be interpreted cautiously. Not applicable.
Complementary and alternative medicine (CAM) therapies are increasingly popular; however, comprehensive data on their usage patterns and types remain limited, especially in South Korea. We investigated the patterns and economic impact of CAM use in thyroid cancer after lobectomy. We utilized data from the MASTER study, a prospective, multicenter, randomized, controlled trial on patients with differentiated thyroid cancer post-lobectomy. Data on CAM usage in 1,166 patients at baseline and at 3, 6, and 12 months postoperatively were included. Logistic regression quantified the effect of levothyroxine treatment on CAM usage. CAM use was reported by 58% of participants. Dietary nutritional products were the most used CAM modality, with usage rates of 42.5% at baseline, decreasing to 37.7% at 12 months. Exercise and physical therapies also showed significant differences, with 19.2% using these modalities at baseline, increasing to 27.1% at 12 months. The median cost for CAM varied, with dietary products consistently costing 144 USD (200,000 KRW) and exercise costs rising from 144 USD (200,000 KRW) to 288 USD (400,000 KRW) over time. Patients on levothyroxine were less likely to use CAM, with an odds ratio (OR) of 0.57 (95% confidence interval [CI] = 0.45-0.72, P < 0.001). However, levothyroxine users who did use CAM were more likely to use multiple CAM modalities, with an OR of 3.66 (95% CI = 1.88-7.14, P = 0.001) at baseline, though this association did not remain significant later. CAM is integrated into thyroid cancer treatment, indicating a need for healthcare professionals to discuss its safety and effective care integration.