Frontiers in Endocrinology最新文献

Introduction: Childhood growth hormone deficiency (GHD) is an endocrine disorder characterized by reduced secretion of growth hormone (GH), leading to impaired linear growth and delayed developmental milestones. Recent studies suggest that GHD is associated with cognitive, socio-emotional, and behavioral impairments, potentially via altered neurodevelopment, with neuroimaging studies revealing changes in brain morphology and broader GH-related effects on the central nervous system. The thalamus, a major subcortical relay integrating sensory, motor and cognitive information, has received limited attention in neuroimaging studies of children with GHD. This study aimed to investigate morphological alterations and characterize lateralization patterns of thalamic nuclei in children with GHD.

Methods: Fifteen children diagnosed with GHD and fifteen age- and sex-matched children with idiopathic short stature (ISS) were recruited. The pituitary gland was segmented using ITK-SNAP software. Thalamic nuclei were delineated and parcellated into ten regions using Bayesian MRI methods and a probabilistic atlas. Lateralization indices were calculated as: ((Left - Right)/(Left + Right)) × 100. Group comparisons and correlation analyses were conducted with age and sex as covariates. All volumes were normalized to total intracranial volume (tICV).

Results: Children with GHD exhibited a significantly smaller pituitary gland volume compared to those with ISS, even after adjustment for age, sex, and tICV. In children with GHD, the anteroventral (AV) thalamic nucleus showed increased volume, and the ventral anterior (VA) nucleus exhibited significantly greater leftward asymmetry compared to ISS. Moreover, there was a significant positive correlation between the lateralization index (LI) of the AV nucleus and serum IGF-1 levels (p = 0.022) and between the LI of the VA nucleus and serum IGF-1 levels (p = 0.022). Similarly, the LI of the AV nucleus was significantly positively correlated with serum IGFBP-3 levels (p = 0.022), and there was also a significant correlation between the LI of the VA nucleus and serum IGFBP-3 levels (p = 0.033).

Conclusion: The observed leftward lateralization in the anterior thalamic nuclei, together with associations with serum IGF-1 and IGFBP-3 levels, suggests that thalamic lateralization reflects a neurodevelopmental adaptation to disrupted GH signaling. These findings suggest that GH/IGF activity shapes subcortical development in a dose-dependent manner and reveal structural adaptations in hormone-sensitive regions to early endocrine disruption.

Background: Vision-threatening diabetic retinopathy (VTDR) is a severe complication of type 2 diabetes mellitus (T2DM), particularly prevalent in patients with prolonged disease duration, poor glycemic control, and systemic comorbidities. This condition frequently progresses asymptomatically toward irreversible blindness without timely intervention. The early identification of VTDR is challenging due to the lack of validated biomarkers and a reliance on subjective clinical assessments. This study aimed to develop and validate an interpretable machine learning (ML) model to detect VTDR among patients with diabetic retinopathy (DR).

Methods: Retrospective clinical data from T2DM patients with DR were extracted from the electronic medical records at our hospital and categorized into VTDR and non-VTDR (defined as mild-to-moderate non-proliferative diabetic retinopathy) groups. The dataset was partitioned into training and testing sets (7:3 ratio). Eight ML models were trained and evaluated using metrics such as Area Under the Curve (AUC), accuracy, and recall. Model performance was evaluated using a comprehensive scoring system (total score = 64). Shapley Additive Explanations (SHAP) were used to interpret the best-performing model. A web-based application was developed to demonstrate potential clinical utility.

Results: Among 1,124 enrolled patients, the prevalence of VTDR was 36.9%. Key associated factors included diabetic treatment, T2DM duration, glycated hemoglobin levels, albuminuria, and anemia. The Support Vector Machine (SVM) model demonstrated superior performance, with an AUC of 0.879, accuracy of 0.837, precision of 0.833, Brier score of 0.129, and an F1 score of 0.756, outperforming the other ML models. The SVM model achieved the highest total score (57/64) in the testing cohort. Furthermore, decision curve analysis and calibration curves confirmed the robustness and reliability of the models. A simplified calculator derived from the SHAP feature importance rankings maintained strong diagnostic capacity.

Conclusion: The interpretable SVM model effectively detected VTDR among patients with DR using routine clinical data. While requiring external validation, this study serves as a proof-of-concept for a cost-effective screening tool that could assist clinicians in prioritizing high-risk patients and facilitating early intervention to prevent irreversible vision impairment.

Premature ovarian failure (POF) is a multifactorial disorder characterized by the progressive decline of ovarian function, in which autoimmune factors account for approximately 10%-30% of cases. Accumulating evidence has demonstrated that immune-related mediators, including regulatory T cells (Tregs), interferon-γ (IFN-γ), and T helper 17 (Th17) cells, play pivotal regulatory roles in its initiation and progression. In recent years, the gut-liver axis and its potential mechanistic links with POF have emerged as a research hotspot in this field. Notably, these pathways are closely associated with the expression and functional balance of key immune mediators such as Tregs, IFN-γ, and Th17 cells. Based on the bridging role of immune cytokines between POF and the gut-liver axis, we propose a novel conceptual framework in which immune cytokines serve as a central hub to systematically elucidate the intrinsic connections among POF, gut microbiota dysbiosis, and bile acid metabolism. Furthermore, we highlight the current limitations of existing studies in this area. This perspective may provide a new theoretical framework for understanding the pathogenesis of POF and holds significant scientific value. Importantly, it may also offer novel insights and potential evidence for expanding clinical diagnostic and therapeutic strategies.

Introduction: Bone Mineral Density (BMD) is a critical determinant of osteoporosis diagnosis and fracture risk. Absence of normative BMD data for Sri Lankans has necessitated reliance on Caucasian references, potentially misestimating the BMD. This study aimed to establish age-related BMD trends for optimal bone health management.

Methods: A retrospective correlational analysis was conducted on 10,946 adults (4,005 men, 6,941 women; 21-80 years) who underwent lumbar spine and hip scans using Hologic Dual Energy X-ray absorptiometry at five private health institutions in Western Province. Individuals with medical conditions or treatments known to affect bone metabolism were excluded.

Results: BMD values showed strong positive correlations across lumbar spine and hips (r = 0.61 - 0.94, p < 0.001) with negligible bias between hips (mean difference ≈ 0.003 g/cm2). Minor right - left hip differences appeared only in 21- 30 age group (p < 0.05). Males had consistently higher BMD than females. In females, lumbar BMD peaked at 31-40 years (0.980 g/cm2) and declined thereafter (F = 279.76, p < 0.001; η² = 0.156); hip BMD peaked at 41-50 years (~0.95 g/cm2) and declined after 50 years (~0.04-0.06 g/cm2 /decade). In males, lumbar BMD peaked at 31-40 years (0.997 g/cm2) with modest decline (F = 4.73, p < 0.001; η² = 0.006), while hip BMD remained stable until 60, then decreased (~0.03 g/cm2 /decade). Contralateral hip BMD showed strong symmetry, supporting the reliability of single-hip measurements in clinical practice. Higher body mass index was positively associated with BMD in both sexes, particularly in women. Years since menopause accounted for a substantial portion of variance (15%-19%) in BMD, with trabecular-rich lumbar spine exhibiting faster early loss compared to cortical-rich hips, which declined more gradually in later decades. Compared with Caucasian reference data, Sri Lankan participants displayed consistently lower BMD, with the greatest deficits observed in postmenopausal women (up to 15% lower), highlighting the need for population-specific reference ranges.

Discussion: These findings demonstrate the need for population-specific BMD reference values to improve diagnostic accuracy and guide clinical management of osteoporosis and osteopenia, particularly in postmenopausal women and older adults.

Background: Atrial fibrillation (AF) develops along the cardiometabolic continuum, where visceral adiposity and early atrial dysfunction may precede overt disease. We aimed to identify independent predictors of new- onset and recurrent AF in middle-aged individuals with cardiometabolic risk.

Methods: This observational cohort included 240 outpatients (40-60 years; 71 controls, 77 new-onset AF, 92 recurrent AF). Conventional anthropometric parameters (body mass index, body roundness index) and biochemical markers (fasting glucose, uric acid, creatinine clearance, inflammatory markers and high-sensitivity troponin I- hsTnI) were assessed. A comprehensive echocardiographic assessment including left atrial reservoir strain (LASr), electromechanical delay (EMD), and epicardial adipose tissue (EAT) were analyzed. Binary logistic regression and ROC analyses were performed.

Results: New-onset AF was independently associated with fasting glucose (OR 3.604; 95% CI 1.338-9.704; p=0.011), EAT thickness (OR 1.479; p=0.006), electromechanical delay (OR 1.043; p=0.001), uric acid (OR 1.006; p=0.026), and lower LASr (OR 0.944; p=0.045). Among the evaluated parameters, EAT demonstrated the highest discriminatory ability for new-onset AF (AUC 0.664; p<0.001). Recurrent AF was independently associated with age (OR 1.122; p<0.001), BMI (OR 1.209; p=0.028), hsTnI (OR 3.546; p<0.001), and lower LASr (OR 0.845; p<0.001). LASr showed good discriminatory performance for recurrent AF (AUC 0.781; p<0.001).

Conclusion: These findings demonstrate that visceral adiposity and metabolic alterations are independently associated with atrial dysfunction and atrial fibrillation in middle-aged individuals with cardiometabolic risk.

Familial partial lipodystrophy (FPLD) is a rare inherited disorder characterized by selective loss of subcutaneous fat and severe metabolic complications. Eight subtypes of FPLD have been described to date, most of which are caused by variants in genes involved in adipocyte differentiation and lipid metabolism. The most common form, FPLD type 2, is caused by heterozygous variants in the LMNA gene, whereas much rarer forms, such as FPLD type 6, are associated with biallelic variants in LIPE. Here, we describe five patients carrying novel or ultrarare pathogenic variants in LMNA (p.Lys117Arg, p.Asn195Tyr, p.Ser239Arg, p.Lys515Glu) and LIPE (homozygous p.Val1068GlyfsTer102), thereby expanding the known genetic and phenotypic spectrum of FPLD. All individuals exhibited abnormal fat distribution and metabolic disturbances, with considerable interindividual variability in the extent and pattern of adipose tissue loss and accumulation. LMNA-related cases showed cardiac involvement, whereas the LIPE-related case presented peculiar patterns of fat redistribution and specific clinical features. These findings underscore the importance of genetic testing in patients with otherwise unexplained lipodystrophy to facilitate early diagnosis, guide personalized management, enable family screening, and support long-term multidisciplinary follow-up for monitoring metabolic, cardiovascular, and systemic complications.

Osteoporosis (OP) is a growing global health concern, characterized by reduced bone mass, deterioration of bone microarchitecture, and consequently increased bone fragility. The brain-bone axis, a complex regulatory network encompassing the nervous, endocrine, and immune systems, elucidates the central role of the brain in regulating bone homeostasis. Consequently, this axis has become a major focus of interdisciplinary research into the pathogenesis of OP. However, the current understanding of the descending regulatory pathways from the brain to the bone remains incomplete. Therefore, this paper preliminarily explores the mechanisms and experimental evidence of different descending regulatory pathways from a new perspective. It integrates multiple descending regulatory pathways, discusses some of their interrelationships, and reveals the complex network nature of central bone metabolism regulation. Our objective is to elucidate the role of the central nervous system (CNS) in OP pathogenesis, thereby offering new insights and directions for future research on its prevention and treatment.

Background: Bone mineral density (BMD) and bone-related parameters are essential for osteoporosis detection. Different screening modalities are used, including quantitative ultrasound (QUS) and dual-energy X-ray absorptiometry (DXA). This systematic review aimed to evaluate the correlation and clinical utility of DXA and QUS measurements.

Methods: A literature search (2005-2025) was conducted in PubMed, Scopus, Web of Science, EMBASE, Google Scholar, and Cochrane Library for English-language studies. A narrative synthesis was performed to summarize the study characteristics and outcomes.

Results: Of the 1,247 identified records, 24 studies met the inclusion criteria. DXA and QUS were used to assess bone parameters, such as BMD, bone mineral content (BMC), speed of sound (SOS), broadband ultrasound attenuation (BAU), and stiffness index (SI). The correlation between DXA and QUS varied widely (r = 0.17-0.86), with variable diagnostic performance across studies. Studies involving postmenopausal women and older populations reported similar trends, whereas the findings were inconsistent in pediatric and disease-specific populations.

Conclusion: QUS is suitable for preliminary screening, especially in resource-limited settings, but cannot replace DXA for definitive diagnosis. Further well-designed studies with longer follow-up are required to better define the role of QUS in osteoporosis screening.

Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD420251146250.