Frontiers in Endocrinology最新文献

{"title":"Integrated pituitary adaptations to the low estrogen state.","authors":"Tiffany K Miles, Angela K Odle, Ashley K Herdman, Lillian G Clark, Stephanie D Byrum, Alex Lagasse, Anessa Haney, Angus M MacNicol, Gwen V Childs, Melanie C MacNicol","doi":"10.3389/fendo.2026.1920998","DOIUrl":"https://doi.org/10.3389/fendo.2026.1920998","url":null,"abstract":"<p><strong>Introduction: </strong>Estrogen's broad trophic effects on anterior pituitary function are not fully understood. The compound 4-vinyl cyclohexene diepoxide (VCD) induces early ovarian failure and reduced E2 production, which may differentially affect anterior pituitary cells. We recently identified transcriptomic changes in pituitary gonadotropes at the single-cell level in females treated with VCD for 20 days, which were acyclic, with low serum estradiol (E2) levels and 8-12-fold increases in gonadotropins 138 days later.</p><p><strong>Materials and methods: </strong>We tested vehicle-control and VCD-treated female mice in metabolic cages and assayed serum hormone levels by EIA, and pituitary cell transcripts by qRT-PCR and single-cell RNA-seq.</p><p><strong>Results: </strong>VCD-treated mice showed normal metabolic health. Compared with controls, VCD-treated females exhibited a 5-fold elevation in serum pituitary thyroid-stimulating hormone (TSH) levels and near-normal thyroid hormone levels. Pituitary <i>Tshb</i> mRNA levels were reduced, and pituitary <i>Gh, Prl</i>, and <i>Pomc</i> mRNA levels were unchanged. Serum growth hormone (GH) levels were higher in VCD-treated mice than in controls 62 days after the start of treatment (perimenopause) and then reduced to control levels after 118-138 days. Ingenuity Pathway Analyses (IPA) of upregulated differentially expressed gene (DEG) transcripts predicted activation of G protein-mediated signaling pathways in one scRNA-seq somatotrope subcluster and in the thyrotrope and lactotrope clusters. In contrast, downregulated DEGs in corticotropes and the remaining two somatotrope clusters predicted downregulation of critical signaling pathways.</p><p><strong>Discussion: </strong>The unchanged pituitary <i>Gh, Prl</i>, and <i>Pomc</i> mRNA levels correlated with unchanged serum levels. The interim rise in serum GH 62 days after treatment agrees with reports of perimenopausal responses due to estrogen spikes. Reduced pituitary <i>Tshb</i> correlates with the recently reported reduced expression in gonadotropes. IPA analysis of upregulated DEGs in thyrotrope clusters predicted the activation of canonical signaling pathways that support elevated serum TSH levels. The near-normal thyroid hormone levels suggest subclinical hypothyroidism in menopausal women. Downregulated DEGs in corticotropes and in two somatotrope subclusters predicted compromised stress and metabolic responses. Finally, reduced multihormone gene expression suggested compromised plasticity in a low-estrogen environment. These different responses to a sustained low-estrogen state, such as that seen in menopause, reflect the diversity of estrogen's trophic actions.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1920998"},"PeriodicalIF":5.7,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13677488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing fracture risk prediction: established assessment tools and emerging HR-pQCT-based approaches.","authors":"Raveen K Sidhu, Meghan G Donaldson, Steven K Boyd","doi":"10.3389/fendo.2026.1916830","DOIUrl":"https://doi.org/10.3389/fendo.2026.1916830","url":null,"abstract":"<p><p>Osteoporotic fractures, or fragility fractures, pose a substantial global healthcare burden. Individuals who experience them report significant declines in their quality of life. Identifying individuals at risk of fragility fractures is key to reducing the future fracture burden. However, due to demographic shifts, the proportion of older adults is growing globally. As fracture risk rises with age, an increase in the incidence of osteoporotic fractures is also anticipated. However, existing screening initiatives and fracture risk assessment tools remain challenged in identifying individuals at risk of experiencing osteoporotic fractures. To adapt to the predicted incidence of fragility fractures, knowledge of established fracture risk tools and emerging approaches is needed to inform the development of future fracture prediction tools. Correspondingly, this narrative review presents an overview of established fracture risk assessment tools, including FRAX, FRAXplus, CAROC, Garvan, and QFracture, which use clinical risk factors and frequently, bone mineral density estimates, to produce fracture risk prediction scores. We review methods, advantages, limitations, and performance of the established tools in detail. Later, we highlight emerging fracture risk assessment tools that integrate direct assessment of bone using high-resolution peripheral quantitative computed tomography (HR-pQCT). The advantages and limitations of the emerging HR-pQCT-based fracture risk assessment models are also reviewed in detail. Finally, future directions for fracture risk assessment tool development are discussed.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1916830"},"PeriodicalIF":5.7,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13679622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149227600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hormonal signaling in glioblastoma: emerging roles in stemness and tumor plasticity.","authors":"Jessica García-Sánchez, Alicia Cañas-Linares, Patricia Garcia-Lopez","doi":"10.3389/fendo.2026.1924678","DOIUrl":"https://doi.org/10.3389/fendo.2026.1924678","url":null,"abstract":"<p><p>Glioblastoma (GBM) is characterized by pronounced cell-state plasticity and functional heterogeneity, which drive therapeutic resistance, tumor recurrence, and disease evolution. Although these processes have traditionally been viewed through a predominantly genomic perspective, emerging evidence identifies endocrine signaling as a critical regulator of glioblastoma cell states. In this review, we propose that hormones function not as independent signaling pathways or merely as promoters of tumor growth, but as systemic regulators that integrate physiological and microenvironmental signals to modulate transitions among stem-like, proliferative, invasive, and treatment-resistant cellular states. We analyzed the current evidence on the roles of sex steroids, glucocorticoids, the IGF/insulin axis, melatonin, thyroid hormones, and prolactin, highlighting how these endocrine signals converge on common molecular nodes, including PI3K/AKT/mTOR, MAPK/ERK, JAK/STAT3, and epigenetic regulators such as EZH2, to coordinate stemness-associated programs, adaptive cell-state responses, and therapeutic adaptation. We also discussed the dual nature of various hormonal axes, including differential activity of estrogen receptor isoforms, the role of the androgen receptor in maintaining self-renewal, the impact of glucocorticoids on adaptive cellular reprogramming, and the ability of melatonin to destabilize stem-like cellular states. Finally, we discuss how sex-based differences in GBM incidence and outcome -driven by both biological and non-biological factors- influence diagnosis, access to treatment, and current interpretations of the global epidemiology of glioblastoma. Collectively, we propose a conceptual framework that redefines GBM as an endocrine-modulated disease, in which hormonal signaling may modulate tumor cell state adaptation. This perspective provides a basis for developing therapeutic strategies that target shared molecular convergence nodes while integrating the biological complexity of GBM with its broader clinical and socioeconomic context.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1924678"},"PeriodicalIF":5.7,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13678582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149227750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of antenatal corticosteroid exposure on glycemic control in preterm infants assessed by continuous glucose monitoring: preliminary results from a single center study.","authors":"Irene Bonato, Andrea Calandrino, Samuele Caruggi, Marcella Battaglini, Francesco Vinci, Gaia Cipresso, Carolina Montobbio, Chiara Andreato, Giorgia Brigati, Luca Antonio Ramenghi","doi":"10.3389/fendo.2026.1847988","DOIUrl":"10.3389/fendo.2026.1847988","url":null,"abstract":"<p><strong>Background: </strong>Antenatal corticosteroids (ACS) are routinely administered to women at risk of preterm delivery to improve neonatal respiratory outcomes. However, ACS exposure has been associated with neonatal hypoglycemia, and its impact on overall glycemic control and variability-particularly at earlier gestational ages-remains incompletely defined.</p><p><strong>Objectives: </strong>To evaluate glycemic control using continuous glucose monitoring (CGM) in preterm infants exposed to ACS and to assess the influence of timing of administration and gestational age on glycemic patterns.</p><p><strong>Methods: </strong>This prospective single-center cohort study included preterm infants born at <35 weeks of gestation and admitted to a level III neonatal intensive care unit between February 2023 and August 2024. Infants were classified according to ACS exposure as complete course, partial course, or no exposure. CGM was performed during the first 48 hours of life. Hypoglycemic (<45 mg/dL) and hyperglycemic (>180 mg/dL) events, as well as glycemic variability assessed by the mean amplitude of glycemic excursions (MAGE), were analyzed. Subgroup analyses were conducted based on the interval between ACS administration and delivery (≤7 days vs >7 days) and gestational age (<34 vs ≥34 weeks). Statistical significance was adjusted using the Benjamini-Hochberg procedure.</p><p><strong>Results: </strong>Sixty-four infants were included (41 complete ACS, 15 partial ACS, 8 no ACS). Baseline characteristics were comparable among groups. During the first day of life, hypoglycemic events occurred exclusively in infants exposed to a complete course of ACS (p = 0.005), predominantly in those exposed within seven days prior to delivery. This difference was not observed on the second day. Hyperglycemic events were significantly more frequent in infants born before 34 weeks of gestation (p = 0.005). Glycemic variability, assessed by MAGE, did not differ significantly according to ACS exposure, timing, or gestational age.</p><p><strong>Conclusions: </strong>Exposure to a complete and recent course of ACS is associated with an increased risk of early neonatal hypoglycemia in preterm infants, particularly within the first 24 hours of life. CGM enables detailed assessment of glycemic instability and may support improved metabolic monitoring in this high-risk population.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1847988"},"PeriodicalIF":5.7,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NADPH oxidase 4 as a source of hydrogen peroxide can regulate norepinephrine levels and vascular contraction.","authors":"Heike Brendel, Jennifer Mittag, Nicole Bechmann, Amna Shahid Mehmood-Ashraf, Antje Schauer, Patrick Diaba-Nuhoho, Mirko Peitzsch, Graeme Eisenhofer, Stefan R Bornstein, Henning Morawietz, Coy Brunssen","doi":"10.3389/fendo.2026.1932927","DOIUrl":"10.3389/fendo.2026.1932927","url":null,"abstract":"<p><strong>Introduction: </strong>The adrenal glands play a pivotal role in maintaining physiological homeostasis, and disturbance in their function can lead to significant clinical disorders, including hypertension, and adrenal insufficiency. Reactive oxygen species (ROS), once considered merely byproducts of cellular metabolism, are now recognized as critical signaling molecules within the adrenal cortex and medulla. Among the major enzymatic sources of ROS are NADPH oxidases (Nox). Dysregulation of Nox-derived ROS has been linked to altered steroidogenesis, oxidative stress- mediated adrenal damage, and tumorigenic processes. We aimed to elucidate the role of Nox4 on adrenal function under healthy conditions.</p><p><strong>Methods: </strong>Using Nox4-knockout mouse model, adrenal effects were assessed by histological analysis, real-time PCR, and cathecholamine quantification using HPLC-ECD and LC-MS/MS. Cardiovascular function was evaluated by echocardiography, blood pressure measurements, and ex vivo vascular function analysis.</p><p><strong>Results: </strong>Here, we demonstrated that Nox4 is expressed in the mouse adrenal gland, and its deletion led to decreased hydrogen peroxide production, diminished dopamine beta-hydroxylase mRNA expression, and reduced norepinephrine levels. In chromaffin cells, treatment with hydrogen peroxide stimulated catecholamine release and increased dopamine beta-hydroxylase expression, indicating a regulatory role of hydrogen peroxide in catecholamine synthesis and secretion. Further analysis of the physiological consequences of reduced norepinephrine levels in Nox4^-/- mice revealed decreased alpha-1 adrenergic receptor expression and impaired adrenergic vascular contraction, while cardiac function remained unaffected. In a model of physical activity, Nox4 depletion resulted in smaller adrenal glands and lower urinary norepinephrine concentrations, further explaining diminished physical activity of Nox4^-/- mice.</p><p><strong>Conclusion: </strong>Our findings provide evidence that Nox4-derived H₂O₂ plays a role in norepinephrine release and norepinephrine-mediated functions. Hence, loss of Nox4 impairs vascular contractility and reduces physical activity performance, highlighting the physiological importance of Nox4 in adrenal function.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1932927"},"PeriodicalIF":5.7,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in urinary biomarker profiles in patients with nephrotic-range proteinuria with and without hypoalbuminemia: a single-center cross-sectional study.","authors":"Mohan Liu, Yingnan Liang, Zhijia Zhang, Jiajia Bai, Zhenjie Chen, Jingwei Zhou","doi":"10.3389/fendo.2026.1938326","DOIUrl":"10.3389/fendo.2026.1938326","url":null,"abstract":"<p><strong>Background: </strong>Patients with chronic kidney disease (CKD) presenting as nephrotic-range proteinuria (NR, ≥3.5g/d) exhibit distinct clinical phenotypes with and without hypoalbuminemia. The underlying mechanisms need further investigation.</p><p><strong>Methods: </strong>This retrospective study included patients with CKD hospitalized over the past two years with baseline 24-hour urine total protein (24-hUTP) exceeding 3.5g. Based on whether their baseline serum albumin (ALB) levels were ≤30 g/L, patients were assigned to two groups: the nephrotic syndrome (NS) group and the isolated nephropathy-range proteinuria (isolated NR) group. Clinical indicators and urine tubular injury biomarkers were compared between the two groups. The Spearman correlation coefficient was used to analyze the association between clinical indicators and urinary biomarker profiles. Urinary biomarkers and the isolated NR phenotype were evaluated for their independent association using multivariate logistic regression analysis.</p><p><strong>Results: </strong>In all, 134 patients were divided into 83 isolated NR and 51 NS groups. Urinary transferrin (uTRF) and N-acetyl-β-D-glucosaminidase (uNAG) were higher in the NS group than in the isolated NR group. The isolated NR group, in contrast, had significant high level of urinary retinol-binding protein (uRBP). Additionally, the two groups' uRBP exhibited distinct correlation patterns with proteinuria. Multivariate logistic regression study demonstrated that uRBP and uTRF were independently linked to the phenotypes after controlling for relevant variables.</p><p><strong>Conclusions: </strong>Patients with NR with and without hypoalbuminemia exhibited distinct urinary biomarker profiles. Higher uRBP levels in patients without hypoalbuminemia may indicate differences in proximal tubular handling of low-molecular-weight proteins. In contrast, higher uTRF and uNAG levels in patients with hypoalbuminemia may reflect greater glomerular permeability abnormalities accompanied by tubular cellular injury. These findings are hypothesis-generating, and the potential involvement of megalin-mediated protein handling requires direct experimental and histopathological validation.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1938326"},"PeriodicalIF":5.7,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CagriSema versus Semaglutide 2.4 mg monotherapy for weight management in adults with overweight or obesity, with or without type 2 diabetes: a systematic review, meta-analysis, and trial sequential analysis.","authors":"Zehra Khatoon Rasool, Rajvi Shah, Ansharah E Zinnia Batool, Rutvi Shah, Mariam Khachatryan, Sushant Bhardwaj, Ahmad Ali, Meeran Atta, Pugazhandhi Bakthavatchalam, Mirza Muhammad Hadeed Khawar, Muneeb Khawar","doi":"10.3389/fendo.2026.1903335","DOIUrl":"10.3389/fendo.2026.1903335","url":null,"abstract":"<p><strong>Introduction: </strong>Semaglutide 2.4 mg is the reference pharmacotherapy for weight management, yet many patients do not reach ambitious weight-loss targets. CagriSema, a fixed-dose combination of cagrilintide and semaglutide, may offer additional benefit through complementary mechanisms. We quantified its incremental efficacy and safety against semaglutide 2.4 mg monotherapy in adults with overweight or obesity, with and without type 2 diabetes.</p><p><strong>Methods: </strong>This PRISMA 2020-compliant review (PROSPERO CRD420261380458) searched PubMed, Embase, Cochrane CENTRAL, ScienceDirect, ClinicalTrials.gov and WHO ICTRP to 30 June 2026 for randomised controlled trials comparing CagriSema with semaglutide 2.4 mg or placebo. Effects were pooled within two prespecified comparator strata using random-effects models with restricted maximum likelihood estimation of τ² and a Hartung-Knapp-Sidik-Jonkman small-sample adjustment, with prediction intervals, leave-one-out and phase-3a-restricted sensitivity analyses, trial sequential analysis.</p><p><strong>Results: </strong>Five trials (4,746 unique participants) were included. Versus semaglutide 2.4 mg, CagriSema produced greater weight loss (mean difference -6.89 percentage points, 95% CI -8.70 to -5.06; I² = 33%; prediction interval -8.91 to -4.86), a greater absolute reduction in body weight (-7.16 kg, 95% CI -9.15 to -5.17) and in body-mass index (-2.41 kg/m², 95% CI -2.83 to -1.99), and roughly twice the likelihood of reaching a 20% reduction (RR 2.10, 95% CI 1.78 to 2.47). Waist circumference fell further (-4.07 cm, 95% CI -5.10 to -3.04). No incremental glycaemic benefit was detected, with intervals for glycated haemoglobin (-0.07, 95% CI -0.14 to 0.01) and fasting plasma glucose lying entirely within prespecified minimal important differences. Injection-site reactions were more frequent (RR 3.14, 95% CI 1.42 to 6.96); gastrointestinal adverse events were not significantly increased under the primary model (RR 1.09, 95% CI 0.97 to 1.21).</p><p><strong>Conclusion: </strong>CagriSema produces clinically meaningful additional weight loss and modest improvements in surrogate cardiometabolic measures compared with semaglutide 2.4 mg alone, at the cost of more frequent injection-site reactions and, at most, modestly more frequent gastrointestinal events. The evidence is insufficient to determine whether serious adverse events or neoplasms differ between treatments, and long-term durability, cardiovascular outcomes and body composition remain undetermined.</p><p><strong>Systematic review registration: </strong>https://www.crd.york.ac.uk/prospero/, identifier CRD420261380458.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1903335"},"PeriodicalIF":5.7,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcome-specific value of longitudinal clinical information and model complexity for dynamic prediction of type 2 diabetes-related outcomes: a pooled landmarking study.","authors":"Meiling Fu, Xiaohong Liu, Ting Shi, Yuxuan Lu, Jie Zou, Xiaowei Huang, Qingmei Pan, Yun Chen, Yinqin Zhong","doi":"10.3389/fendo.2026.1964592","DOIUrl":"10.3389/fendo.2026.1964592","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the outcome-specific incremental value of longitudinal clinical history and model complexity for annual dynamic prediction of multiple type 2 diabetes-related outcomes using pooled landmarking.</p><p><strong>Methods: </strong>We included 646 patients with complete annual records from baseline through year 3. Landmark times at years 1 and 2 were used to predict the first recorded occurrence of hypertension, coronary heart disease, diabetic kidney disease, diabetic retinopathy, or metabolic dysfunction-associated steatotic liver disease during the subsequent year. Four progressively expanded feature sets were compared using elastic-net logistic regression and Light Gradient Boosting Machine. The primary history-current estimand was a paired within-algorithm contrast with the risk set, validation splits, preprocessing, tuning, calibration, and evaluation records held constant. Internal validation used patient-level repeated nested cross-validation. We also evaluated fully nested model selection and model-development stability using 500 patient-level bootstrap replicates with out-of-bag evaluation.</p><p><strong>Results: </strong>Pooled out-of-fold area under the receiver operating characteristic curve ranged from 0.722 to 0.952 across the five representative models. The paired history-current comparison showed higher AUC for hypertension with elastic-net (ΔAUC 0.097, 95% confidence interval 0.057 to 0.136) and LightGBM (0.118, 0.081 to 0.158), and for metabolic dysfunction-associated steatotic liver disease with elastic-net (0.022, 0.002 to 0.042) and LightGBM (0.025, 0.009 to 0.041). The other three outcomes showed no comparable improvement. Algorithm differences were modest and outcome dependent.</p><p><strong>Conclusion: </strong>In this single-center cohort with complete annual T0-T3 follow-up, the incremental value of longitudinal information and model complexity was outcome specific. Longitudinal history showed greater benefit for selected outcomes, whereas algorithm differences were modest and outcome dependent. The smaller MASLD signal was supported primarily by the pooled L1-L2 analysis. Independent external validation is required before clinical application.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1964592"},"PeriodicalIF":5.7,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Healthy sleep pattern is associated with reduced risk of incident thyroid disease: a prospective cohort study from the UK Biobank.","authors":"Jingxue Sun, Yanmeizhi Wu, Xiaoyu Zhao, Lulu Sun, Huanran Lv, Ruitong Sun, Tianshu Han, Hong Qiao","doi":"10.3389/fendo.2026.1859828","DOIUrl":"10.3389/fendo.2026.1859828","url":null,"abstract":"<p><strong>Introduction: </strong>The longitudinal association between sleep behaviors and the incidence of various thyroid diseases remains unclear. This study aimed to prospectively investigate the association between a healthy sleep score and the risk of incident thyroid diseases using data from the UK Biobank.</p><p><strong>Methods: </strong>This prospective cohort study included 499, 084 adults aged 37-73 years from the UK Biobank. A healthy sleep score ranging from 0 to 5 was constructed based on five self-reported sleep behaviors: chronotype, sleep duration, insomnia, snoring, and daytime excessive sleepiness. Participants with missing information on sleep behaviors were excluded from the construction of the healthy sleep score. Incident outcomes included overall thyroid disease, hypothyroidism, nontoxic goiter, thyrotoxicosis, thyroiditis, thyroid cancer, and iodine deficiency-related diseases.</p><p><strong>Results: </strong>After adjustment for multiple covariates, higher healthy sleep scores were dose-dependently associated with lower risks of overall thyroid disease, hypothyroidism, nontoxic goiter, and thyrotoxicosis. Compared with participants with poor sleep patterns (scores of 0-1), those with the healthiest sleep pattern (score of 5) had significantly lower risks of overall thyroid disease (24% [17%-31%]), hypothyroidism (25% [17%-32%]), nontoxic goiter (26% [7%-41%]), and thyrotoxicosis (32% [15%-45%]). Among the five sleep components, the absence of frequent daytime excessive sleepiness showed a particularly evident association with lower risks of thyroid disease. Furthermore, interaction analyses suggested that the inverse association between the healthy sleep score and the risk of overall thyroid disease may vary by sex, BMI, and diabetes status, with more pronounced associations observed among women, individuals with obesity, and those without diabetes.</p><p><strong>Conclusion: </strong>Higher healthy sleep scores were associated with lower risks of incident overall thyroid disease, hypothyroidism, nontoxic goiter, and thyrotoxicosis. Among the individual sleep components, the absence of frequent daytime excessive sleepiness showed the strongest association with a lower risk of thyroid disease.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1859828"},"PeriodicalIF":5.7,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microglia as candidate links between hormonal signals and neuronal circuits in polycystic ovary syndrome: evidence gaps and a research agenda.","authors":"Hongtao Li, Tong Yin, Yichen Wang, Yixuan Wang, Xiaoyuan Lin, Xinyan Jia, Wei Yi, Han Yang","doi":"10.3389/fendo.2026.1952469","DOIUrl":"10.3389/fendo.2026.1952469","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) combines reproductive endocrine dysfunction with metabolic, autonomic, and neurobehavioral phenotypes, yet the contribution of brain microglia remains uncertain. We conducted a structured narrative review that separates human PCOS evidence, PCOS-like animal findings, PCOS-related cellular observations, and non-PCOS mechanistic bridges. Only three heterogeneous PCOS-like studies directly assessed microglial outcomes, and none established a conserved microglial state, microglial necessity, a complete hormone-microglia-neuron causal chain, or human relevance. We therefore propose the PCOS Neuroimmune-Endocrine Triangular Network (PNETN), a falsifiable framework linking endocrine and metabolic signals, context-dependent microglial states, and neuronal circuits regulating GnRH/KNDy activity, luteinizing-hormone dynamics, ovulation, metabolism, autonomic function, and behavior. The framework defines criteria for causal promotion, including cell identity, regional specificity, temporal precedence, selective perturbation, rescue, orthogonal functional readouts, and independent replication. Microglia should currently be regarded as candidate contributors, not established clinical targets.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1952469"},"PeriodicalIF":5.7,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}