Frontiers in Endocrinology最新文献

Epilepsy can cause metabolic disorders, and metabolic abnormalities can also trigger epilepsy, forming a bidirectional pathological cycle. Over the past century, from the earliest use of ketogenic diets to treat epilepsy, it has been confirmed that metabolic intervention can control seizures. Subsequent studies have gradually revealed that metabolic disorders such as glucose abnormality and vitamin B6 deficiency can directly induce epilepsy, while epileptic seizures themselves can cause lactic acidosis, electrolyte imbalance and other internal environment disorders. With the breakthroughs in metabolomics technology, the research on epilepsy and metabolism has entered a systematic stage, and their relationship has attracted increasing attention. However, current reviews mostly focus on the isolated analysis of a single metabolic element (such as iron, vitamin D), lacking a systematic integration of multiple metabolic elements. This review for the first time integrates the changes of seven major metabolic elements (glucose, lipids, vitamins, minerals, water, adenosine triphosphate, uric acid) in the onset, progression and treatment of epilepsy; summarizes the clinical associations between metabolic diseases (diabetes mellitus, alcoholism, uremia) and epilepsy; reveals the specific metabolic changes in childhood epilepsy; and emphasizes the importance of epilepsy metabolomics data. It provides a reference for basic research and a metabolic monitoring framework for clinicians.

Background: The global incidence of thyroid nodules is rising substantially. The correlation between excessive iodine intake and an elevated risk of thyroid nodules remains a subject of debate.

Objective: To evaluate the categorical and quantitative dose-response associations between iodine status levels and the risk of thyroid nodules.

Methods: We systematically searched PubMed, Web of science, Embase, Cochrane Library and Scopus for studies published before December 2025 that investigated the association between iodine status and thyroid nodules, without language restrictions. The categorical association was assessed by pooling odds ratios (ORs) for thyroid nodules across different iodine status categories, using the adequate category as the reference. The continuous dose-response association was evaluated using random-effects generalized least squares spline models. The primary outcome was the prevalence of thyroid nodules at different iodine status statuses.

Results: This meta-analysis included 25 cross-sectional studies comprising 54621 participants (57.7% women) and 13569 thyroid nodule events. In categorical analyses, participants in the iodine deficiency (median urinary iodine concentration [UIC]: 50 μg/L) showed higher odds of thyroid nodules (OR = 1.28, 95%CI=1.09-1.50) compared to the adequate iodine category (median UIC, 150 μg/L). No significant association was found for both the more-than-adequate iodine (median UIC, 250 μg/L) category and excessive iodine (median UIC, 350 μg/L) categories (OR = 1.02, 95% CI = 0.93-1.11; OR = 1.13, 95%CI=0.98-1.30, respectively). Nine studies reporting continuous UIC outcomes, the mean difference (MD) between participants with and without nodules was 4.11 (95% CI, 2.51 to 5.71, P < 0.01). Continuous dose-response analysis revealed a significant U-shaped nonlinear correlation (P for nonlinearity < 0.001), with increased risks at both deficient and excessive iodine levels. These associations remained consistent in analyses by unadjusted variables of sex, age and BMI. Further analysis stratified by geographical factors also revealed similar correlation tendency.

Conclusions: The relationship between iodine intake and thyroid nodule risk follows a U-shaped, nonlinear pattern, where both deficiency and excess are associated with increased risks. More than adequate iodine intake showed a trend toward a lower prevalence of thyroid nodules. However, this observation should be interpreted with caution due to wide confidence intervals, heterogeneity, and potential residual confounding.

Systematic review registration: PROSPERO, https://www.crd.york.ac.uk/PROSPERO/view/CRD420251236621, identifier CRD420251236621.

Objective: Radioactive iodine (RAI) therapy is a cornerstone treatment for Graves' hyperthyroidism (GH), yet failure rates remain significant due to the complexity of individual patient responses. Traditional fixed-dose or simple calculated-dose methods often fail to account for non-linear interactions among clinical features.

Methods: We retrospectively analyzed data from 1,292 GH patients who received initial RAI therapy between June 2018 and July 2024. Comprehensive pre-treatment clinical, laboratory, and imaging data, including age, gender, FT4, 3-hour radioactive iodine uptake (RAIU 3h), thyroid weight, and thyroid receptor antibodies (TRAb), were collected. Stepwise regression with the Akaike Information Criterion (AIC) was employed for feature selection, identifying nine optimal predictors. Six machine learning algorithms were compared, with performance evaluated using AUC, Brier score, and Decision Curve Analysis (DCA). SHapley Additive exPlanations (SHAP) analysis provided model interpretability.

Results: The final cohort, comprising 1,292 patients (61.3% female, median age 37 years), achieved a 75.8% remission rate. Nine significant variables were identified as optimal predictors: gender, age, history of antithyroid drug use, disease course over 2 years, total iodine dose (TID), free thyroxine (FT4), RAIU 3h, thyroid weight, and TRAb. Among the algorithms tested, the Random Forest (RF) model demonstrated superior performance, achieving an AUC of 0.950 on the independent test set and a Brier score of 0.067, indicating excellent discrimination and calibration. SHAP analysis confirmed RAIU 3h, FT4, age, and thyroid weight as the most influential features, providing clinical transparency.

Conclusion: The developed interpretable machine learning framework offers a precise, personalized tool for predicting RAI outcomes, potentially guiding optimizing dosing strategies to reduce treatment failure.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder characterized by a high incidence rate and multiple complications, posing significant threats to women's health and quality of life. The etiology of PCOS involves a complex interplay of genetic, metabolic, hormonal, immunological and environmental factors, though its precise mechanisms remain incompletely understood. This review explores the roles of oxidative stress, autophagy, ferroptosis, epigenetic modifications, post-translational modifications, chronic low-grade inflammation, and gut microbiota in the pathogenesis of PCOS. Current therapeutic strategies often combine lifestyle modifications with pharmacological interventions to address the multifaceted symptoms of PCOS. Drawing on the latest research, this review highlights advanced glycation end products (AGEs), sex hormone-binding globulin (SHBG), and microRNAs (miRNAs) as promising targets for PCOS prevention and treatment. Future research should focus on developing targeted drugs for these molecular pathways, offering new avenues for managing PCOS. This review will provide a scientific foundation for advancing PCOS treatment strategies.

Background: Evidence on the efficacy and safety of radioligand therapy (RLT) in lung neuroendocrine tumors (LNETs) remains scarce. The limited data available, derived mainly from retrospective analyses are based on small patient cohorts and heterogeneous treatment protocols. The objective of this study was to assess the efficacy and safety of RLT in patients with SSTR-positive LNETs treated with either [¹⁷⁷Lu]Lu-DOTA-TATE or tandem therapy with [⁹⁰Y]Y-DOTA-TATE/[¹⁷⁷Lu]Lu-DOTA-TATE at Polish ENETS Center of Excellence.

Methods: We conducted a retrospective analysis of 22 LNET patients who received RLT and had complete follow-up data. Treatment response and survival outcomes were evaluated. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Prognostic associations with PFS and OS were explored using univariate and multivariable Cox proportional hazards models, treatment-related AE were graded according to CTCAE.

Results: A total of 22 patients with LNETs (Med. 61 years; 68.2% male) were included. Histology comprised 31.8% typical carcinoid, 54.5% atypical carcinoid, and 13.6% LNET G3. 14 patients received [¹⁷⁷Lu]Lu-DOTA-TATE and 8 tandem [⁹⁰Y]Y/[¹⁷⁷Lu]Lu-DOTA-TATE. At a median follow-up of 54 months, median PFS and OS were 16.0 months (95% CI: 11.2-20.8) and 62.0 months (95% CI: 30.7-93.3), respectively. PFS was longer in patients with high SSTR uptake (34vs16 months; p=0.021) and, in unadjusted exploratory analyses, in those treated with tandem therapy (34vs16 months; p=0.037). OS differed significantly by histology and by prior chemotherapy, while FDG-avid disease was associated with shorter PFS and OS. However, these subgroup comparisons are based on a very small sample and should be regarded as exploratory and interpreted with caution. Treatment was generally well tolerated, with hematologic toxicity being the most common.

Conclusions: RLT demonstrated signals of clinically meaningful activity and an acceptable safety profile in patients with advanced LNETs in this small retrospective cohort. Outcomes were numerically more favorable in individuals with high SSTR uptake and in those treated with tandem therapy, but the study was not designed to compare treatment regimens. These exploratory findings should be regarded as hypothesis-generating only and do not provide evidence of comparative efficacy.

Objectives: To assess the prevalence and determinants of macrovascular complications (coronary artery disease, stroke, and diabetic foot) among adults living with T2DM in rural Bangladesh.

Methods: A population-based cross-sectional study was conducted between December 2023 and September 2024, involving 1094 adults with diagnosed T2DM from rural areas of three regions/divisions in Bangladesh. Data were collected through household interviews, physical examination, and medical record reviews. Macrovascular complications were identified using clinical criteria and documented diagnosis. The leverage of six machine learning (ML) algorithms were applied in identifying influential variables associated with these complications.

Results: The prevalence of coronary artery disease (CAD), stroke, and diabetic foot was 11.2%, 5.3%, and 9.1%, respectively. The Light Gradient Boosting Machine algorithm performed best for CAD and diabetic foot, with ROC values of 98.8% and 92.6%, respectively, while Random Forest showed the best performance for stroke with a ROC of 99%. These models also outperformed others across accuracy, precision, F1 score, and calibration. Across models, common predictors included older age, longer diabetes duration, diabetes onset at age 45 years or above, and smoking. Hypertension and elevated cholesterol were linked to CAD and stroke. Coexisting microvascular complications were also identified.

Conclusions: This study identified a substantial burden of macrovascular complications among rural adults with T2DM, with CAD, stroke, and diabetic foot emerging as the most prevalent outcomes. Advanced age, longer duration of diabetes, smoking, hypertension, and elevated cholesterol were consistently associated with these complications, highlighting the need for intensified cardiometabolic risk control within primary care. These findings underscore the urgency of strengthening integrated diabetes-cardiovascular management in rural Bangladesh to reduce the progression and impact of these major vascular outcomes.

A puzzling metabolic question is the emergence of rapid-onset diabetes in the postnatal period of pre-term infants without the usual preceding prodromal characteristics. The etio-pathophysiology is unclear, but continues to be a concern, since the prevalence remains a significant health issue. We hypothesize that this new diabetes type is hypoxemia-driven from compromised ventilation via periodic breathing or apnea of infancy during the immediate postnatal period. The resulting intermittent hypoxia leads to elevated cytosolic chloride levels in pancreatic beta-cells affecting insulin secretion and disturbed glucose transporter (GLUT) 4 function resulting from lowered With-no-lysine (k) kinase (WNK)1 levels in the skeletal musculature. In addition, the peripheral cellular effects are coupled with prolonged elevated sympathetic outflow elicited by the disrupted breathing. This mini-review discusses current research gaps and provides insights into potential interventions for the widespread epidemic of Type 1 and Type 2 diabetes.

Objective: To explore the effects of different intensities of endurance training combined with resistance training on the bones of growing male rats, and to provide the optimal exercise plan for bone mineral accumulation in adolescents.

Methods: Thirty 6-week-old male Sprague-Dawley rats were randomly divided into 5 groups: control (C), resistance training (R), low-intensity endurance + resistance (LR), moderate-intensity endurance + resistance (MR), and high-intensity interval + resistance (HR). After 8 weeks of exercise intervention, the bone mineral density, bone microstructure, bone mechanical properties and bone remodeling of rats were assessed. One-way analysis of variance (ANOVA) was used to test the results obtained by the detection methods.

Results: The body weight of the exercise group was lower than that of the control group. The endurance and resistance training group (LR/MR/HR) had significantly higher bone mineral density than the control group (p's < 0.05). There was no difference in bone metabolism markers among the groups. In the result of bone volume fraction, only the MR group was significantly higher than the control group (p = 0.03); the number of trabeculae showed statistical differences in the LR group and the MR group (p's < 0.05). Each exercise group showed significantly higher maximum load and fracture stress than the control group (p's ≤ 0.001), but no difference in maximum strain was shown.

Conclusion: Combined endurance and resistance training improved bone mineral density and mechanical strength in growing male rats, with moderate-intensity endurance training showing the most consistent improvements in bone microarchitecture.

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder often associated with disturbances in glucose metabolism and insulin resistance (IR), increasing the risk of type 2 diabetes (T2DM). Standard assessment of glucose dysregulations and IR requires laboratory tests, but simple anthropometric indices, including BMI, WHtR, WHR, VAI, LAP, BAI, BRI and ABSI, may provide non-invasive tools for early risk screening. Their predictive value and optimal cut-off points for detecting glucose dysregulation and IR in PCOS remain unclear.

Objectives: This study aims to evaluate the clinical utility of anthropometric indices in identifying glucose dysregulation in women with PCOS, and to provide prognostic insight with potential cut-off points for these indices.

Methods: This cross-sectional study included 49 women with PCOS according to Rotterdam criteria. Anthropometric measurements (BMI, WC, WHR, WHtR, VAI, BAI, LAP, BRI, ABSI) and fasting biochemical parameters (glucose, insulin) were collected. Correlations between indices and carbohydrate disturbances were assessed using Pearson or Spearman coefficients. The predictive ability of anthropometric indices for glucose dysregulations and IR were evaluated using ROC curve analysis, including AUC, sensitivity, specificity, and optimal cut-off points, while logistic regression quantified the strength of associations.

Results: BMI, WHtR, BAI, VAI, LAP, and BRI were significantly correlated with fasting glucose and insulin levels, indicating a strong link between adiposity and IR in women with PCOS. Among these indices, VAI showed the highest predictive performance for elevated HOMA-IR (AUC = 0.933, cut-off point 0.99; sensitivity 85.7, specificity 90.5%), followed by LAP (AUC = 0.883, cut-off point 27.9) and BMI (AUC = 0.852, cut off point 27 kg/m²). WHtR, WC, and BRI also demonstrated significant predictive value (AUCs 0.821-0.831). Logistic regression revealed the strongest associations for BMI ≥27.25 kg/m² and VAI ≥1.07 (OR = 57.0; 95% CI 9.41-345.15; p<0.001), with WC, WHtR, LAP, BAI, and BRI also showed significant predictive value for IR.

Conclusion: Anthropometric indices, particularly VAI, LAP, and BMI, reliably predicts glucose dysregulations and IR in women with PCOS. These simple, non-invasive measurements may serve as useful screening tools for early identifications of glucose dysregulation, aiding risk stratification and guiding further metabolic assessment.

Isolated Premature Thelarche (PT) is a common clinical issue in pediatric endocrinology. Because its early presentation resembles that of Central Precocious Puberty (CPP), which requires intervention, its management is highly controversial, caught between "active intervention" and "watchful waiting." This leads to inconsistent clinical practices and significant anxiety for affected families. This review aims to move beyond this traditional dichotomy by conducting an in-depth analysis of the natural history, pathophysiological mechanisms, diagnostic criteria, and progression risks of PT. We propose a new paradigm for a tiered, individualized management approach based on risk stratification, providing a clear, evidence-based pathway for clinical decision-making. Through a comprehensive review of recent clinical studies, reviews, and expert consensus, this paper analyzes the theoretical basis and evidence supporting a "watchful waiting" strategy. It defines the rigorous initial evaluation and dynamic monitoring protocols required for its implementation and clarifies the quantitative indicators for transitioning from "observation" to "active intervention." For children with typical PT-characterized by a normal growth rate, no significant bone age advancement, a prepubertal pelvic ultrasound, and a very low basal luteinizing hormone level-"watchful waiting" or "active surveillance" is a safe, effective, and preferred management strategy. This is an active medical monitoring process, not passive waiting. "Active intervention" (i.e., Gonadotropin-Releasing Hormone agonist therapy) should be strictly limited to the few "progressive" cases that show sustained pubertal progression, growth acceleration, and significant bone age advancement during follow-up, and are confirmed as CPP by a Gonadotropin-Releasing Hormone stimulation test. The risk-stratified management pathway proposed herein aims to effectively address the clinical dilemma, avoid over-treatment, and achieve individualized, precise management for children with PT.