Frontiers in Endocrinology最新文献

Osteoporosis (OP) is a metabolic bone disease that affects more than 10 million people in the USA and leads to over two million fractures every year. The disease results in serious long-term disability and death in a large number of patients. Bone mineral density (BMD) measurement is the current standard in assessing fracture risk; however, the majority of fractures cannot be explained by BMD alone. Bone is a composite material of mineral, organic matrix, and water. While bone mineral provides stiffness and strength, collagen provides ductility and the ability to absorb energy before fracturing, and water provides viscoelasticity and poroelasticity. These bone components are arranged in a complex hierarchical structure. Both material composition and physical structure contribute to the unique strength of bone. The contribution of mineral to bone's mechanical properties has dominated scientific thinking for decades, partly because collagen and water are inaccessible using X-ray based techniques. Accurate evaluation of bone requires information about its components (mineral, collagen, water) and structure (cortical porosity, trabecular microstructure), which are all important in maintaining the mechanical integrity of bone. Magnetic resonance imaging (MRI) is routinely used to diagnose soft tissue diseases, but bone is "invisible" with clinical MRI due to its short transverse relaxation time. This review article discusses using ultrashort echo time (UTE) sequences to evaluate bone composition and structure. Both morphological and quantitative UTE MRI techniques are introduced. Their applications in osteoporosis are also briefly discussed. These UTE-MRI advancements hold great potential for improving the diagnosis and management of osteoporosis and other metabolic bone diseases by providing a more comprehensive assessment of bone quantity and quality.

Background: Pheochromocytomas (PCCs) and paragangliomas (PGLs) (PPGLs) are rare tumours arising from the chromaffin cells. There is evidence suggesting a link between hypoxemia and PPGLs. Chronic hypoxia can lead to gain of function somatic variants in the EPAS1 gene that encodes for hypoxia-inducible factor 2-alpha (HIF-2α), involved in PPGL tumorigenesis.

Objective: To describe a rare case of PCC in a pulmonary transplant patient and characterize the tumour's genetic background.

Clinical case: A 47 year-old man underwent a lung transplant for chronic obstructive pulmonary disease associated with alpha-1 antitrypsin deficiency. He required home oxygen therapy for 3 years prior to transplant. Nineteen years after transplant, a CT-scan revealed a 5.8 cm x 3.9 cm heterogeneous right adrenal mass (HU of 7). Initial assessments indicated elevated 24-hour urinary catecholamines. Consequently, the patient underwent laparoscopic right adrenalectomy, confirming the PCC diagnosis.

Genetic studies: 1) Germline PPGL multigene panel: After consent, the patient underwent a panel of 14 susceptibility genes for PPGLs that revealed no pathogenic variants. 2) Somatic genetic analysis for EPAS1 gene found no variants. However, tumoral RNA sequencing unveiled activation of the HIF pathway.

Conclusion: We describe a rare case of PCC in a pulmonary transplant recipient, with genetic analyses showing no germline pathogenic variants and no somatic variants in the EPAS1 gene. RNA sequencing highlighted HIF pathway activation and angiogenic implications. Further research is necessary to elucidate the genetic and molecular mechanisms underlying PCCs in this specific case and determine its link with hypoxemia in the context of pulmonary disease.

Objective: This study aims to investigate the relationship between metabolic dysfunction-associated fatty liver disease (MAFLD) and sex hormones and sex hormone-binding globulin (SHBG) in boys with obesity.

Methods: Retrospective analysis of metabolic indicators and sex hormone levels in boys with obesity who sought medical attention at the First People's Hospital of Lianyungang City from January 2020 to December 2023. Based on abdominal ultrasound results, they were categorized into a simple obesity group and MAFLD group, and differences between the two groups were compared. Utilizing logistic regression analysis to explore the risk factors for developing MAFLD, and through the construction of Receiver Operating Characteristic (ROC) curves, conducting a preliminary assessment of the diagnostic value for MAFLD.

Results: A total of 155 male children with obesity were included in the study, mean age of 11.07 ± 1.53 years. Children in the MAFLD group had higher levels of height[(159.49 ± 12.73)cm vs.(155.55 ± 10.50)cm], weight[(82.32 ± 18.75)kg vs.(68.28 ± 15.00)kg], BMI[(32.08 ± 4.49)kg/m² vs.(27.85 ± 4.21)kg/m²],fasting insulin[33.42(24.07,43.93)uIU/ml vs.23.91(15.72,31.52)uIU/ml],HOMA-IR[7.27(5.26,10.71) vs.4.87(3.27,6.86)],fastingC-peptide[1409.00(1175.00,1668.00)pmol/L vs.1020.00(849.05,1303.00)pmol/L], WBC[(7.85 ± 1.80)×10⁹/L vs.(7.15 ± 1.42)×10⁹/L], HbA1c[5.40(5.30,5.70)% vs.(5.30(5.20,5.60)%],ALT[48.00(27.00,80.00)U/L vs.19.00(15.00,26.50)U/L], and AST[31.00(24.00,60.00)U/L vs.21.00(18.50, 26.00)U/L] compared to the simple obesity group (P<0.05). Children in the MAFLD group had lower levels of HDL[(1.05 ± 0.21)mmol/L vs.(1.16 ± 0.26)mmol/L], testosterone [42.41(30.33,143.28)ng/dl vs.125.41(23.41,221.57)ng/dl], and SHBG[13.20(9.10,17.30)nmol/l vs.19.60(13.50,29.85)nmol/l] compared to the simple obesity group (P<0.05). Logistic regression showed that BMI, testosterone, and SHBG were independent risk factors for MAFLD in boys, and ROC curve analysis indicated their potential value in the early diagnosis of MAFLD.

Conclusion: BMI, testosterone, and SHBG are independent risk factors for the occurrence of MAFLD in boys with obesity. To control the occurrence of MAFLD, it is essential to address the root cause of the high growth rate of obesity. The roles of testosterone and SHBG in MAFLD merit further research.

Background: The Magnesium Depletion Score (MDS) is a novel indicator that integrates multiple factors to assess systemic magnesium depletion. However, its association with hyperuricemia (HUA) prevalence remains unclear. This study aims to investigate the relationship between MDS and the prevalence of HUA.

Methods: A cross-sectional analysis was conducted using data from the 2007-2018 National Health and Nutrition Examination Survey (NHANES). The MDS was derived by integrating multiple risk factors associated with magnesium depletion: the use of diuretics and proton pump inhibitors (PPI), estimated glomerular filtration rate (eGFR), and alcohol consumption exceeding recommended thresholds. Univariable and multivariable logistic regression models assessed the association between MDS and HUA. Subgroup and sensitivity analyses, including the exclusion of gout patients, further evaluated this association.

Results: Among 18,761 participants, higher MDS were associated with an increased prevalence of HUA. Multivariable logistic regression confirmed a significant positive association between MDS and HUA (OR = 1.73, 95% CI = 1.62-1.84). Restricted cubic splines (RCS) further characterized the non-linear relationship between MDS and HUA prevalence. Subgroup analysis indicated a positive association between MDS and HUA, with significant interactions observed for sex and body mass index. Sensitivity and additional analyses reinforced the robustness of these findings.

Conclusion: Among U.S. adults, higher MDS were significantly associated with an increased prevalence of HUA, suggesting that interventions targeting magnesium deficiency could be beneficial in reducing HUA prevalence within this population. However, prospective studies are needed to further confirm these findings.

Objective: To analyze the impact of maternal gestational weight gain (GWG) on adverse outcomes for mothers and infants.

Methods: A retrospective analysis was conducted, collecting relevant information on 9,058 singleton pregnancies and newborns from prenatal check-ups and deliveries at Guangdong Women and Children Hospital from 2017 to 2022. The subjects were grouped according to different GWG, and logistic regression was used to analyze the impact of GWG on adverse outcomes, including hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), large-for-gestational-age infants (LGA), small-for-gestational-age infants (SGA), and preterm births.

Results: Among the 9058 participants included in the study, there were 438 cases (4.8%) of HDP, including 266 cases (2.9%) of gestational hypertension and 172 cases (1.9%) of preeclampsia. Additionally, there were 2018 cases (22.3%) of GDM; Among the adverse birth outcomes for newborns, the prevalence was 9.7% for SGA, 9.9% for LGA, 1.4% for early/mid-term preterm births, and 4.2% for late preterm births. After adjusting for confounding factors, the results showed that, excessive GWG was a risk factor for HDP (OR=1.829, P<0.05) and LGA (OR=1.792, P<0.05) compared to the normal gestational weight gain group. Insufficient GWG increased the risk of GDM (OR=2.203, P<0.05), SGA (OR=1.474, P<0.05) and was also a risk factor for early/mid-term preterm infants (OR=3.326, P<0.05) and late preterm infants (OR=1.715, P<0.05).

Conclusion: Excessive GWG is a risk factor for the occurrence of HDP and LGA, while insufficient GWG increases the risk of GDM, SGA and preterm infants (especially early/mid-term preterm infants). Therefore, it is recommended to strengthen the monitoring of weight changes during pregnancy in women of childbearing age, guide nutritional management during pregnancy, and keep GWG within a reasonable range to prevent adverse outcomes for mothers and infants.

Oxidative stress plays a pivotal role in male infertility by impairing sperm function through various molecular mechanisms. This review explores the impact of excessive reactive oxygen species (ROS) on spermatozoa, particularly focusing on lipid peroxidation, DNA fragmentation, and protein oxidation. Lipid peroxidation damages sperm membranes, reducing fluidity and motility. ROS-induced DNA fragmentation compromises genetic integrity, potentially leading to infertility and adverse offspring outcomes. Protein oxidation alters key structural proteins, impairing sperm motility and the ability to fertilize an egg. The primary sources of oxidative stress in sperm include leukocyte activity, mitochondrial dysfunction, and environmental factors such as smoking and pollution. Despite the presence of natural antioxidant defenses, spermatozoa are particularly vulnerable due to limited repair mechanisms. The review highlights the importance of early intervention through antioxidant therapies and lifestyle changes to mitigate the detrimental effects of oxidative stress on male fertility. Further research is essential to enhance therapeutic approaches and improve reproductive outcomes.

Introduction: Numerous physiological systems, such as the functioning of the immune system, bone health, and the regulation of expression of genes, depend critically on vitamin D. Considering the significance of vitamin D for health, it is critical to understand how it is metabolized and the factors that affect its levels.

Methods: The objective of this study was to develop and validate an LC-MS/MS method to examine the effects of light exposure and dietary vitamin D consumption on the levels of vitamin D and its metabolites in a mouse model under consistent growth conditions throughout the year. Serum and hair samples from mice were analyzed under various experimental conditions for vitamin D and its metabolites using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The experimental conditions included a vitamin D-deficient diet, a vitamin D-standard diet, and changes in ambient light exposure ranging from complete darkness to a regular light-dark cycle.

Results: Mice fed a standard vitamin D diet and exposed to a regular light-dark cycle exhibited significantly higher levels of 25OHD₃ in both serum and hair, indicating the synergistic effect of dietary vitamin D intake and light exposure. Mice fed a standard vitamin D diet but kept in continuous darkness showed moderately elevated 25OHD₃ levels, demonstrating the efficacy of dietary vitamin D in maintaining adequate levels despite the absence of light. Conversely, mice fed a vitamin D-deficient diet and housed in darkness displayed 25OHD₃ levels below the limit of quantification, highlighting the combined detrimental effects of dietary deficiency and lack of light exposure.

Discussion: This study provides valuable insights into the complex interplay between dietary vitamin D intake, light exposure, and the regulation of vitamin D metabolism in mice. Moreover, our results underscore the potential implications for human health, suggesting the importance of adequate vitamin D intake and sunlight exposure in maintaining optimal vitamin D levels. Further research in this area has the potential to unveil additional factors influencing vitamin D metabolism, offering valuable insights into strategies for optimizing vitamin D levels in both animal models and human subjects.

Background: The aim of the study was to explore a radiomic model that could assist physicians in the diagnosis of central precocious puberty (CPP). A predictive model based on radiomic features (RFs), extracted form magnetic resonance imaging (MRI) of the pituitary gland, was thus developed to distinguish between CPP and control subjects.

Methods: 45 girls with confirmed diagnosis of CPP (CA:8.4 ± 0.9 yr) according to the current criteria and 47 age-matched pre-pubertal control subjects (CA:8.7 ± 1.2 yr) were retrospectively enrolled. Two readers (R1, R2) blindly segmented the pituitary gland on MRI studies for RFs and performed a manual estimation of the pituitary volume. Radiomics was compared against pituitary volume in terms of predictive performances (metrics: ROC-AUC, accuracy, sensitivity and specificity) and reliability (metric: intraclass correlation coefficient, ICC). Pearson correlation between RFs and auxological, biochemical, and ultrasound data was also computed.

Results: Two different radiomic parameters, Shape Surface Volume Ratio and Glrlm Gray Level Non-Uniformity, predicted CPP with a high diagnostic accuracy (ROC-AUC 0.81 ± 0.08) through the application of our ML algorithm. Anthropometric variables were not confounding factors of these RFs suggesting that premature thelarche and/or pubarche would not be potentially misclassified. The selected RFs correlated with baseline and peak LH (p < 0.05) after GnRH stimulation. The diagnostic sensitivity was improved compared to pituitary volume only (0.76 versus 0.68, p<0.001) and demonstrated higher inter-reader reliability (ICC>0.57 versus ICC=0.46).

Discussion: Radiomics is a promising tool to diagnose CPP as it reflects also functional aspects. Further studies are warranted to validate these preliminary data.