Search Results (110)

Pancreatic neuroendocrine neoplasms (PNENs) are a diverse group of rare tumor subtypes, representing less than 2% of all pancreatic tumors. Often detected late in the clinical course, they are associated with high rates of morbidity and mortality. Hereditary syndromes such as multiple endocrine neoplasia type-1 and von Hippel–Lindau are associated with the development of PNENs, although only a small portion of total tumors have a genetic basis. This review aims to explore the recent advances in laboratory diagnostics, imaging modalities, medical management, and surgical approaches to hormone-producing PNENs (including some common, less common, and some rare subtypes), with the goal of assisting physicians in the integration of evidence-based information into their practice. Full article

In healthy humans, insulin at physiological concentrations exerts acute vasodilatory actions on both resistance and terminal arterioles, leading, respectively, to increased total blood flow and the microvascular network volume being perfused. The process of increasing capillary network volume is frequently referred to as “capillary recruitment”. Together these two vascular actions of insulin enhance the delivery of oxygen, nutrients, and insulin itself to tissues. Both processes are diminished by insulin resistance. Here we examined interactions between insulin’s acute (within 2 h) actions on blood pressure (both central and peripheral) and on capillary recruitment in healthy controls and in four distinct groups of people with heightened cardio-metabolic disease (CMD) risk: individuals with obesity, metabolic syndrome, and type 1 or type 2 diabetes. Insulin increased microvascular blood volume (MBV) more effectively in controls than in each of the four CMD risk groups (p < 0.001). Conversely, insulin lowered both central and peripheral systolic pressure (p < 0.05 or less) in each of the CMD risk groups but not in the controls. The insulin-induced blood pressure decrements were greater in the metabolic syndrome, type 2 diabetes, and obesity groups (p < 0.05 or less) than in the controls. The greater blood pressure declines likely reflect decreased sympathetic baroreceptor reflex tone. These effects on blood pressure combined with the diminished dilation of terminal arterioles due to microvascular insulin resistance in the CMD risk subjects led to decreased distal microvascular perfusion as evidenced by changes in MBV. These findings highlight the complex interplay between insulin’s actions on resistance and terminal arterioles in individuals with a high CMD risk, underscoring the importance of addressing microvascular dysfunction in these conditions. Full article

Background/Objectives: Continuous glucose monitoring (CGM) has transformed diabetes management, with time in range (TIR) emerging as a key glycemic metric. However, TIR lacks sensitivity to glycemic variability, leading to the introduction of time in tight range (TiTR), which defines a narrower range (70–140 mg/dL). This review synthesizes current evidence on TiTR’s clinical relevance and its potential to predict complications. Methods: A literature search was conducted, primarily using PubMed as the main database, to identify studies that specifically evaluate TiTR and its clinical implications, published until February 2025. Results: Preliminary data indicate that a 10% increase in TiTR is associated with a 23.8% reduction in microvascular complications. While TiTR aligns more closely with physiological glucose control, standardized targets remain undefined. Conclusions: This study provides clinicians with insights into optimizing glycemic control beyond traditional metrics. The correlation of TiTR with other glycemic markers and its association with diabetes-related complications suggest that TiTR can complement traditional measures to provide a more comprehensive assessment of glycemic status. From a clinical perspective, incorporating TiTR into routine practice may help personalize treatment strategies, improve risk stratification, and support more precise therapeutic decisions, particularly in patients using continuous glucose monitoring (CGM). Future research should refine TiTR thresholds and evaluate its integration into diabetes management, particularly in populations using advanced technologies. Full article

Objective: To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and clinical, hormonal, and auxological features in girls with idiopathic central precocious puberty (CPP). Methods: This retrospective study included 122 girls diagnosed with idiopathic CPP. Participants were stratified into three groups based on serum 25(OH)D concentrations: deficient (<20 ng/mL), insufficient (20–30 ng/mL), and sufficient (>30 ng/mL). Clinical and hormonal parameters were compared across groups. Spearman’s correlation and multiple linear regression analyses were used to explore the relationship between vitamin D levels and peak luteinizing hormone (LH) response to gonadotropin-releasing hormone (GnRH) stimulation. Results: No significant differences were observed among the vitamin D groups in terms of age at diagnosis, body mass index (BMI), or other auxological measures. However, serum 25(OH)D levels showed a weak but significant positive correlation with LH peak values (rho = 0.23, p = 0.037). In multivariable regression analysis, vitamin D levels remained an independent predictor of LH peak (β = 0.125, p = 0.036), whereas BMI standard deviations (SDS), growth velocity SDS, and age at diagnosis did not show significant associations. Conclusions: Higher serum vitamin D levels are independently associated with greater LH peak responses in girls with idiopathic CPP. These findings support a potential modulatory role of vitamin D in the neuroendocrine mechanisms underlying pubertal onset and warrant further prospective studies to clarify its clinical relevance. Full article

Background/Objectives: Endocrine hormones play critical roles in regulating physiological processes, and previous studies have reported their associations with psychiatric disorders. Levels of endocrine hormones and the risk of developing psychiatric disorders are influenced by both genetic and non-genetic factors. However, the shared genetic basis underlying these associations remains largely unexplored. This study aims to dually evaluate the genetic correlations among endocrine hormones, including thyroid and sex hormones, as well as between endocrine hormone metrics and psychiatric disorders to identify potential shared genetic architectures. Methods: We obtained genome-wide association study summary statistics for six thyroid hormone metrics, three sex hormone metrics, and ten psychiatric disorders from predominantly European-ancestry populations. Genetic correlations were computed using linkage disequilibrium score regression after harmonizing variant data to ensure consistency across studies. Results: Significant genetic correlations were observed among thyroid and sex hormone metrics, indicating a strong shared genetic basis. Sex hormones exhibited multiple genetic correlations with psychiatric disorders, including negative correlations between sex hormone-binding globulin and attention-deficit hyperactivity disorder (ADHD) (p = 3.95 × 10⁻¹²) and major depressive disorder (p = 4.67 × 10⁻⁵), and positive genetic correlations with anorexia nervosa (p = 2.86 × 10⁻¹²) and schizophrenia (p = 2.00 × 10⁻⁴). Testosterone and estradiol had negative genetic correlations with ADHD and major depressive disorder, while testosterone had positive genetic correlations with anorexia nervosa and schizophrenia. Although thyroid hormone metrics did not exhibit Bonferroni-significant genetic correlations, nominal associations were observed, such as a negative genetic correlation between thyroid-stimulating hormone and major depressive disorder (p = 2.33 × 10⁻²). Conclusions: These findings suggest a shared genetic basis between endocrine hormones and psychiatric disorders, particularly for sex hormones. Future studies leveraging larger, more diverse populations are warranted to validate and extend the genetic correlations observed in this study. Full article

Background/Objectives: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autoimmune disorder caused by mutations in the AIRE gene. Approximately 60% of affected females develop premature ovarian insufficiency (POI) by age 30, often most commonly due to steroidogenic autoantibodies. Although APECED is typically diagnosed in childhood, its reproductive implications are underrecognized. This study reports a case of successful fertility preservation in an adult woman with APECED and reviews the relevant literature. Methods: We describe the clinical course of a 37-year-old woman with genetically confirmed APECED who underwent ovarian stimulation for fertility preservation. A comprehensive PubMed search was also conducted to identify English-language case reports on fertility preservation in APECED-associated POI. Results: The patient experienced menarche at age 13, adrenal insufficiency at 14, and menstrual irregularities from age 18. Genetic analysis confirmed an AIRE mutation (NM_000383: exon 11: c.1400+1G>A). Given her relatively high anti-Müllerian hormone level, she opted for fertility preservation and underwent six cycles of ovarian stimulation, resulting in the cryopreservation of 17 mature oocytes. During ovarian stimulation, multiple follicular developments were observed, but serum E2 levels remained low. The literature review identified fewer than 20 reported cases addressing fertility preservation in APECED, highlighting its rarity and the lack of standardized management. Conclusions: Although APECED frequently leads to early POI due to impaired steroidogenesis, residual ovarian function may persist. Early assessment of ovarian reserve and timely fertility counseling are crucial, even in asymptomatic patients or those diagnosed in childhood. Reproductive planning should be integrated into the long-term care of women with APECED. Full article

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), previously referred to as Non-Alcoholic Fatty Liver Disease (NAFLD), is a prevalent chronic liver condition strongly linked to Type 2 Diabetes Mellitus (T2DM) and obesity. Globally, MASLD is the most common cause of chronic liver disease. The bidirectional relationship between MASLD and T2DM underscores the pivotal role of insulin resistance in disease progression, which contributes to hepatic steatosis, oxidative stress, and inflammation, forming a vicious cycle. MASLD is also associated with heightened risks of cardiovascular and chronic kidney diseases, necessitating comprehensive treatment approaches. While lifestyle interventions and weight loss remain the cornerstone of management, their sustainability is challenging. This review highlights the evolving pharmacological landscape targeting MASLD and its advanced form, Metabolic Dysfunction-Associated Steatohepatitis (MASH). Currently, Resmetirom is the only FDA-approved drug for MASH. Current and investigational therapies, including insulin-sensitizing agents like peroxisome proliferator-activated receptor (PPAR) agonists, glucose-lowering drugs such as sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA), drugs that target intermediary metabolism such as Vitamin E, de novo lipogenesis inhibitors, and emerging agents targeting the gut-liver axis and oxidative stress, are explored. These therapies demonstrate promising effects on hepatic steatosis, inflammation, and fibrosis, providing new avenues to address the multifaceted pathophysiology of MASLD. Full article

Retinoic acid (RA) exerts biological effects through RA receptors (RARs) to regulate transcription. RA also elicits rapid, RAR-independent (noncanonical) activities mediated by Cellular RA Binding Protein 1 (CRABP1) to modulate cytosolic signaling. CRABP1 functions by forming protein complexes, named CRABP1 signalosomes, to modulate signal propagation in a cell type-specific manner. This review summarizes multiple CRABP1 signalosomes and their physiological functions. CRABP1 knockout (CKO) mice develop multiple phenotypes progressively throughout the lifespan. These include altered brain function, obesity, and insulin resistance starting at young adult stages, increased vulnerability to heart failure and altered serum exosome profiles in midlife, and motor deterioration and thyroid dysfunction (hypothyroidism) in later life. The mouse Crabp1 gene is tightly regulated by multiple epigenetic mechanisms, whereas human CRABP1 gene dysregulation is associated with multiple human diseases in which age is an important factor. Further, CRABP1 expression in human and mouse thyroid glands gradually increases with aging. This underscores the clinical relevance of CRABP1 signalosomes in maintaining health and the functions of certain cells/organ systems, especially in the thyroid and during the aging process. The CRABP1 sequence is highly conserved, likely due to its functional constraint in forming various signalosomes; its tight regulation ensures proper expression of CRABP1 required for the forming of various signalosomes critical to the health and functions of multiple cell types/organ systems. Finally, CRABP1-specific (without activating RARs) signaling pathway-selective compounds have been designed. It may be an attractive therapeutic strategy to exploit these CRABP1-specific compounds to modulate selective signaling pathways in certain disease conditions, such as thyroid dysfunction, to maximize efficacy while minimizing retinoid toxicity. Full article

Background/Objectives: The association between sexual dysfunction and diabetes is well known, but few studies have investigated its prevalence in type 1 diabetes (T1D). The aim of this study was to evaluate the prevalence of sexual dysfunction in a group of women with T1D, regardless of their age, and to compare its different prevalences in women treated with different insulin regimens. Methods: The population included 77 women affected by T1D, of which 16 were on Multiple Daily Injections (MDI) and 61 on Continuous Subcutaneous Insulin Infusion (45 on Advanced Hybrid Closed Loop System with catheter and 16 on patch pump). All participants completed the Female Sexual Function Index (FSFI), a questionnaire that evaluates several aspects of sexual function. Another questionnaire that evaluated general features, diabetes-specific features and sexual-specific features was proposed to every participant. Results: The overall prevalence of female sexual dysfunction was 49.3%. A correlation was demonstrated between the prevalence of female sexual dysfunction and age; another correlation was found between the prevalence of female sexual dysfunction and dyadic status. No correlation between glycemic control and sexual dysfunction was found. Conclusions: Women with T1D presented a high prevalence of sexual dysfunction, independently from glycometabolic disease control and insulin regimens; on the other hand, a significant correlation was demonstrated with age and dyadic status. Evaluation of sexual function in women with T1D appears to be important in clinical settings independently from disease control. Full article

Background: Plastic pollution driven by human activities has become a critical global issue for human health. A growing literature demonstrates that micro- and nanoplastics (MNPs) contain endocrine-disrupting chemicals (EDCs) and other harmful compounds that enter the body easily, acting as agonists or antagonists for a wide range of hormonal receptors, and promoting endocrine toxicity. Endocrine disruption induced by MNPs occurs through the aberrant activation/inhibition of different signaling pathways that in addition to directly interfering with hormonal balances, trigger apoptosis, oxidative stress, and inflammation in endocrine cells. However, to date, the molecular mechanisms of these contaminants remain not completely elucidated. Furthermore, given the unanimous consensus on the negative impact of MNPs on human health, several methodologies have been developed to detect MNPs and contaminants not only in the environment but also in biological fluids and human tissues. Results: This review comprehensively summarizes the emerging experimental and clinical evidence explaining the mechanisms underlying the toxicity related to chronic plastic pollution in relation to the endocrine system. In addition, the review illustrates the new methodological approaches to detect MNPs in human biological samples, highlighting that employing complementary methods enables the precise characterization and quantification of MNPs. Conclusions: Future studies employing experimental, epidemiological, epigenetic, and multi-omics approaches are essential for understanding the short and long-term effects of MNPs on endocrine glands and developing effective strategies to mitigate their impact on human health. Full article

Background: Vitamin D is essential for neonatal health, with maternal vitamin D status crucial in fetal development and neonatal outcomes. During pregnancy, vitamin D is transferred to the fetus via the placenta, forming an initial reserve. Postnatally, neonates rely on maternal levels and supplementation due to limited sunlight exposure and immature skin synthesis. Objectives: This review evaluates neonatal vitamin D deficiency’s causes and clinical consequences, emphasizing its impact on newborn and infant health. Results: Maternal vitamin D levels strongly correlate with neonatal 25(OH)D concentrations, influencing birth weight, bone development, and overall health. Supplementation during pregnancy reduces the risk of severe deficiencies and rickets, particularly in exclusively breastfed infants who require daily supplementation of 400 IU. Formula-fed infants typically meet requirements through fortified formulas. Preterm infants are at a higher risk of complications like osteopenia and rickets, with mixed evidence on the effectiveness of higher supplementation doses. Vitamin D is critical in skeletal development, immune function, and protection against respiratory infections such as bronchiolitis and pneumonia. Deficiency is associated with respiratory distress syndrome (RDS), atopic dermatitis, and impaired bone mineralization due to reduced placental calcium transport. Conclusions: Vitamin D deficiency during pregnancy and infancy has significant clinical implications, including impaired skeletal and immune development. Maternal and neonatal supplementations are critical to prevent deficiencies, particularly in high-risk groups such as preterm and breastfed infants. Targeted strategies are essential to improve neonatal health outcomes and prevent complications. Full article

Stress responses enable vertebrates to adapt to environmental challenges while maintaining homeostasis. Zebrafish larvae are a valuable model for studying stress regulation due to their genetic accessibility and rapid development. This review examines the integration of zebrafish larvae with water vortex protocols to investigate hypothalamic–pituitary–interrenal (HPI) axis functionality during early development, advancing stress research while adhering to the 3Rs principle. Key publications are reviewed to discuss the potential of water vortices in zebrafish larvae for studying stress responses. These purely physical stressors exploit the innate positive rheotropism of developing zebrafish, offering precise control over timing and strength while avoiding confounding factors associated with chemical or biological interventions. The approach enables reproducible assessments of stress responses. The reviewed publications show advances in understanding cortisol response dynamics, glucocorticoid feedback, and early-life stress-induced changes in HPI axis function. Key findings include detailed cortisol patterns after acute stress, rapid glucocorticoid receptor-mediated feedback regulating cortisol levels, developmental shifts in HPI axis sensitivity, and reduced cortisol reactivity following early-life challenge (ELC). Vortex-driven ELC affects cortisol regulation, neuropeptide expression in the nucleus preopticus, and stress-related gene transcription. Combining zebrafish larvae and vortex protocols provides a robust and innovative platform for investigating stress biology. This approach leverages active, demanding behaviour to study stress mechanisms under controlled conditions, yielding insights with broad applications across vertebrate models while supporting the 3Rs principle. Future studies can build on these findings to address unresolved questions in stress regulation and enhance our understanding of adaptive physiological mechanisms. Full article

A balanced diet and regular physical activity are essential for maintaining musculoskeletal health. Key nutrients such as calcium, vitamin D, and protein are especially important for preventing falls and fractures. While the benefits of these nutrients are well-established, other dietary components have not been studied as extensively. For instance, vegetables, which are rich in nutrients vital for muscle and bone health, play a crucial role in preventing falls and fractures. Over recent decades, a great emphasis has been given to the combinations of nutrients and foods in dietary patterns that may have synergistic or antagonistic effects. Despite the challenges in researching the impact of nutrition and physical activity on musculoskeletal health due to the extensive heterogeneity of the results, healthcare professionals should continue to promote healthy eating and regular physical activity, and these principles should be emphasized in public health initiatives. Ultimately, a sufficient and balanced diet, abundant in plant-based foods and low in processed or discretionary foods, along with consistent physical activity, remains the most effective strategy for the prevention of musculoskeletal issues. This article aims to review the updated literature of recent years on the links between nutrition and physical activity with bone and skeletal muscle health. Full article

Background/Objectives: In contrast to endochondral bone healing, the process of intramembranous bone regeneration is poorly understood. This limits our ability to repair and regenerate the craniofacial skeleton to either correct deformity or optimally heal tissues following injury. While there are several preclinical models of intramembranous regeneration within the craniofacial skeleton, some are not load bearing and others are technically challenging. The goal of this pilot study is therefore to describe a simple method for induction of cortical defects within the mandible that does not involve compounding injury to the surrounding tissues. Methods: Single cortex defects were generated in the mandible body of 8-week-old male and female mice. The extent of bone regeneration within the defect was characterized at days 0, 3, 14, and 28 following defect generation via micro-computed tomography and histology. Conclusions: Observed healing was predictable and reproducible and resulted in intramembranous bone formation. This model will help aid the understanding of intramembranous bone healing in load bearing bones (e.g., mandible) within the craniofacial skeleton Full article

Alex Vermeulen (1927–2023) was a leading Belgian endocrinologist whose name will forever remain linked to testosterone and androgen metabolism. As a dedicated scientist and clinician, he made seminal contributions to endocrinology throughout his career. These included the development of chromatography and radioimmunoassays of steroid hormones. His work also focused on the biological significance and metabolism of corticosteroids and androgens, and he defined key concepts in the role of steroid hormones in the human menstrual cycle, pregnancy, and menopause. His love for math, endocrinology, and problem-solving led to a formula for the estimation of free testosterone in serum, which has not been improved upon to date and is still in use worldwide. He contributed to enhancing our understanding of the role that male sex hormones may play in a variety of clinical problems in endocrinology, including bone health, type 2 diabetes, and, especially, endocrine function in aging males. Alex Vermeulen literally was “a giant in endocrinology”. Beyond his scientific contributions, Vermeulen was a wise and engaging mentor, a Renaissance man, and an aficionado of the finer things in life. He owned an eclectic choice of modern artworks, all of which he bequeathed to the Ghent Museum of Fine Arts, thus significantly enhancing the museum’s art patrimony. Full article