Search Results (175)

Ertugliflozin is a sodium-glucose co-transporter-2 inhibitor that has demonstrated promise as a treatment for hyperinsulinaemia in horses. Despite the frequent use of ertugliflozin in equine clinical practice, the pharmacokinetics of this drug in horses has not been established. The aim of the present study was to determine the pharmacokinetics of one supratherapeutic dose (0.25 mg/kg) of ertugliflozin in eight horses. Horses were defined as being healthy by physical examination, haematological, blood biochemical and oral sugar test (OST) results. Plasma concentrations of ertugliflozin were quantified using high-performance liquid chromatography–tandem mass spectrometry 0, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 14, 18, 24, 30, 36, 48, 60, 72, 96, and 120 h after drug administration enterally. Non-compartmental analysis led to determination of key pharmacokinetic variables, including mean ± SD time to maximum concentration (T_max) of 0.91 ± 0.13 h, maximum measured concentration (C_max) of 267.52 ± 25.37 ng/mL, terminal elimination half-life (T_1/2) of 17.65 ± 3.15 h and apparent oral clearance (CL/F) of 106.95 ± 27.53 mL/h/kg. No clinical signs of adverse effects or blood biochemical abnormalities occurred after drug administration. The results of this study suggest that a single supratherapeutic dose of ertugliflozin in healthy horses is safe. The pharmacokinetics of enterally administered ertugliflozin in horses are similar to pharmacokinetics of the drug in humans and the long T_1/2 makes ertugliflozin suitable for once daily dosing in horses. It is proposed that a starting dose for ertugliflozin in horses be in the range 0.05–0.1 mg/kg. Further pharmacokinetic studies are required to optimise the dose regimen for treating horses with hyperinsulinaemia. Full article

Background: This study aims to systematically review the current literature on the application of radiomic features and artificial intelligence (AI) in the diagnosis and prognosis of common peripheral nerve-related conditions, including carpal tunnel syndrome (CTS), chronic inflammatory demyelinating polyneuropathy (CIDP), polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin abnormalities (POEMS) syndrome, and in distinguishing between benign and malignant tumors. Methods: A comprehensive literature search was conducted in PubMed and Google Scholar for studies published between January 2019 and September 2025. Inclusion criteria comprised studies that used radiomics or AI-based radiomics approaches with diagnostic or prognostic purposes in peripheral nerve disorders. Results: A total of 40 studies were identified, of which 17 met the inclusion criteria. Among these, 9 studies employed magnetic resonance imaging (MRI), including one combined with PET/CT, while 8 used ultrasound (US). Most studies were retrospective and limited by small sample sizes, lack of external validation, and predominance of single-center designs. Conclusions: Since a seminal study published in 2019, there has been increasing evidence supporting the role of radiomics and AI in improving the diagnosis and prognosis of peripheral nerve disorders, particularly using MRI and US. However, significant challenges remain, including variability in imaging data, segmentation complexity, and limited availability of validated datasets. Future advancements in imaging technologies and multidisciplinary collaboration are essential to enhance clinical applicability. Full article

Diabetes mellitus (DM) is a complex metabolic disorder associated with a heightened risk of cardiovascular events, largely driven by a hypercoagulable and hypofibrinolytic state. The pathophysiological interplay between chronic hyperglycemia, oxidative stress, insulin resistance, and systemic inflammation fosters profound alterations in the coagulation cascade, endothelial function, and platelet activity. This narrative review synthesizes evidence from studies published between 2008 and 2026, focusing on coagulation and platelet-related biomarkers selected based on their biological relevance to thrombosis, endothelial dysfunction, and inflammation, as well as the availability of clinical and interventional data across different forms of DM. Although there are numerous biomarkers involved in the pathogenesis of various forms of diabetes, this narrative review critically examines key coagulation biomarkers—including D-dimer, fibrinogen, prothrombin, tissue thromboplastin or tissue factor, P-selectin, soluble urokinase plasminogen activator receptor, thrombomodulin, plasminogen activator inhibitor-1, von Willebrand factor, and β-thromboglobulin—across distinct diabetes subtypes, including type 1, type 2, gestational, and secondary forms linked to endocrinopathies and pancreatic diseases. The literature reveals substantial subtype-specific heterogeneity in hemostatic alterations. For instance, Type 1 DM is characterized by early endothelial dysfunction and platelet activation, while Type 2 DM presents with elevated coagulation factors, impaired fibrinolysis, and a proinflammatory milieu. Gestational DM exhibits pregnancy-specific changes in coagulation, yet distinguishing them from obesity-related effects remains challenging. Secondary diabetes forms, such as those associated with Cushing’s syndrome or pancreatitis, further underscore the diversity in thrombotic risk profiles. Among the coagulation and platelet activation biomarkers reviewed, fibrinogen, P-selectin, and plasminogen activator inhibitor-1 demonstrate the most consistent associations with glycemic control, vascular dysfunction, and therapeutic modulation, particularly in type 2 diabetes, suggesting greater potential for clinical translation. In contrast, evidence for markers such as D-dimer, tissue factor or tissue thromboplastin, and soluble urokinase plasminogen activator receptor remains heterogeneous and insufficient for routine clinical application. By synthesizing mechanistic insights and clinical data, this review highlights the urgent need for subtype-tailored coagulation assessment in diabetes management. A better understanding of the dynamic alterations in coagulation pathways may facilitate earlier detection of vascular complications and inform personalized antithrombotic strategies. Full article

Advances in pediatric oncology have markedly improved survival, shifting attention toward long-term treatment-related morbidity. Targeted agents and immune-based therapies are now widely used across pediatric malignancies and selected non-malignant conditions, often for prolonged periods and during critical windows of growth and development. Because many therapeutic targets regulate physiological pathways involved in growth, pubertal maturation, gonadal function, bone metabolism, and energy homeostasis, clinically relevant endocrine toxicity may emerge during treatment or become apparent only with extended follow-up. This narrative review summarizes pediatric evidence on endocrine and metabolic effects associated with major classes of targeted and immune-based therapies, including tyrosine kinase inhibitors, mTOR inhibitors, MAPK-pathway inhibitors (BRAF/MEK), TRK inhibitors, ALK inhibitors, immune checkpoint inhibitors, and immune effector therapies. Distinct patterns of endocrine vulnerability emerge across drug classes: growth impairment and bone–mineral alterations are most consistently reported with tyrosine kinase inhibitors; weight gain and metabolic changes predominate with MAPK-, TRK-, and ALK-targeted agents; immune checkpoint inhibitors are characterized by early, multi-axis immune-related endocrinopathies with a high likelihood of permanent hormone deficiency once established. In contrast, endocrine abnormalities observed after immune effector therapies largely reflect indirect effects of systemic inflammation, corticosteroid exposure, and prior hematopoietic stem cell transplantation rather than direct endocrine toxicity. Given the limited pediatric-specific data, frequent confounding by multimodal therapy, and the potential for delayed or irreversible endocrine sequelae, structured endocrine monitoring and long-term survivorship care are essential for children exposed to modern anticancer therapies. Full article

Endocrine disorders are increasingly recognized as major contributors to secondary cardiomyopathies, leading to profound alterations in cardiac structure and function. This comprehensive review synthesizes current evidence on the genetic basis of cardiomyopathies associated with endocrine conditions, including primary aldosteronism, Cushing’s syndrome, pheochromocytoma/paraganglioma, acromegaly, thyroid disorders, hyperparathyroidism, and diabetic cardiomyopathy. We examine the contribution of somatic and germline mutations, genetic polymorphisms, shared molecular pathways transforming growth factor-β (TGF-β)/SMAD (TGF-β/SMAD signaling, the renin–angiotensin–aldosterone system, oxidative stress, and calcium handling), sarcomeric gene modifiers, ion channel variants, and epigenetic mechanisms to disease pathogenesis. We propose a conceptual framework distinguishing three major categories of genetic involvement: (i) variants causing the primary endocrinopathy; (ii) genetic modifiers of myocardial susceptibility under conditions of hormonal excess; and (iii) direct pleiotropic effects, whereby single gene variants independently cause both endocrine and cardiac phenotypes. In addition, we discuss genotype–phenotype correlations, ethnic and population differences in genetic susceptibility, the emerging role of polygenic risk scores, and precision medicine approaches. Overall, this review provides an integrated perspective on the complex genetic architecture of endocrine-related cardiomyopathies and outlines practical considerations for genetic testing aimed at improving patient management and clinical outcomes. Full article

Autoimmune thyroid diseases (AITDs), including Hashimoto thyroiditis and Graves’ disease, are the most common autoimmune endocrinopathies, affecting up to 5% of the population. Pathogenetic pathways have not yet been fully elucidated, even though different immune-genetic alterations have been proposed. Specific immune defects presenting with AITDs may serve as an experimentum naturae to study the involvement of a specific pathway in the pathogenesis of the disease. In fact, since immune dysregulation with autoimmunity frequently characterize inborn errors of immunity (IEIs), understanding the mechanisms of immune tolerance breakdown leading to autoimmunity in these conditions may provide useful insight to understand the pathogenesis of AITDs. In this review, we will highlight the main immunological aspects of AITDs and their pathogenesis in IEIs. Full article

Background/Objectives: Immune checkpoint inhibitors (ICIs) have revolutionized the management of several malignancies, including melanoma, non-small cell lung cancer, and urothelial carcinoma. However, these therapies frequently cause endocrine immune-related adverse events (irAEs), such as thyroid dysfunction, hypophysitis, or autoimmune diabetes, and may carry important prognostic implications. This systematic review and meta-analysis aimed to determine the incidence, spectrum, and clinical significance of endocrine irAEs across major tumor types. Methods: Following PRISMA guidelines and PROSPERO registration (CRD42025646504), we systematically searched PubMed, Embase, Cochrane CENTRAL, Web of Science, and Scopus for studies reporting endocrine irAEs in ICI-treated patients. Random-effects meta-analyses estimated pooled hazard ratios (HRs) for overall (OS) and progression-free survival (PFS) and odds ratios (ORs) for adverse events. Subgroup and meta-regression analyses explored associations by cancer type, ICI class, and event severity. Results: Forty-three studies comprising 17,399 patients were included. Endocrine irAEs occurred in 11–30% of patients and were associated with improved OS (HR: 0.60, 95% CI: 0.54–0.67; p < 0.001) and PFS (HR: 0.61, 95% CI: 0.54–0.68; p < 0.001). Severe events were most frequent with pembrolizumab in melanoma and non-small cell lung cancer and with anti-programmed death-ligand 1 therapy in urothelial carcinoma. In exploratory meta-regression analyses accounting for cancer type, ICI subclass, and irAE severity, no statistically significant correlation was observed between the occurrence of endocrine irAEs (OR) and survival benefit (PFS HR: 0.20, 95% CI −0.10 to 0.51; p = 0.19; OS HR: 0.14, p > 0.05). Conclusions: The development of endocrine irAEs coincides with favorable long-term survival outcomes but may represent surrogate markers of immune activation rather than direct predictors of ICI efficacy. However, the lack of consistent ≥ 3-year follow-up across studies warrants cautious interpretation. Routine endocrine monitoring and interdisciplinary management are essential to optimize the safety and effectiveness of immunotherapy. Full article

McCune–Albright Syndrome (MAS) is a rare mosaic disorder caused by somatic activating mutations of the GNAS gene, resulting in constitutive Gsα signaling and a broad spectrum of clinical phenotypes. The syndrome typically presents with fibrous dysplasia (FD) of bone, café-au-lait macules, and endocrinopathies such as gonadotropin-independent precocious puberty, hyperthyroidism, and/or growth hormone excess. FD, which characterizes the skeletal phenotype, results in the replacement of normal bone with disorganized fibro-osseous tissue, often leading to pain, deformities, and increased risk of fractures. This review discusses the following: 1. The molecular biology of the GNAS locus and its relation to the pathophysiology of FD/MAS; 2. The skeletal manifestations of FD/MAS; 3. Bone biomechanics and organizational skeletal aberrations observed in FD/MAS; and 4. Current and future therapeutic strategies for patients with FD/MAS. While there is much current literature available regarding FD/MAS, this review specifically aims to outline core understandings and summarize some of the latest investigations into the genotypic and phenotypic foundations of the disorders, while shedding new light on the biomechanical aberrations observed in skeletal structure within them and comparing them to those observed in related disease processes such as osteoporosis and Paget’s disease. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the hepatic manifestation of systemic metabolic dysregulation, strongly linked to type 2 diabetes, cardiovascular diseases, liver-related complications, and different types of malignancies. Although MASLD is associated with obesity and insulin resistance, it is increasingly recognized that the liver engages in complex crosstalk with several endocrine pathways, including thyroid function, sex and steroid hormone regulation, and growth hormone signaling. The pathophysiology of MASLD is multifactorial and complex, as reflected by its clinical range—from simple steatosis to cirrhosis. MASLD now affects about one-quarter of the global population, with its prevalence rising due to sedentary lifestyles, chronic caloric excess, and endocrine disturbances contributing to disease progression. Given the escalating prevalence of MASLD and its frequent concurrence with various endocrinopathies, understanding this relationship is critical for refining diagnostic accuracy and optimizing therapeutic strategies. This review aims to synthesize contemporary insights into the complex interactions between MASLD and selected endocrine disorders, elucidate underlying pathophysiological mechanisms, and underscore novel treatment paradigms. As MASLD remains a significant clinical challenge worldwide, its intersection with endocrine dysfunctions represents a vital and promising domain for future research and clinical management. Full article

Continuous glucose monitoring (CGM)-based interventions have been predominantly conducted in people with established diabetes. Recently, there has been an increasing interest in using CGM for clinical and research purposes in people without diabetes. In this review, we describe the current evidence regarding the use of CGM in people at high risk of diabetes. To date, there is no strong evidence to support the global implementation of CGM in individuals who are at risk of developing diabetes. However, there are promising results highlighting the benefits of CGM in specific populations such as people living with obesity, prediabetes, gestational diabetes mellitus, metabolic dysfunction-associated steatotic liver disease, other endocrinopathies, and genetic syndromes. Also, CGM has shown promising potential in people with positive islet autoantibodies and pre-symptomatic type 1 diabetes, those treated with medications that induce hyperglycaemia or diabetes, and individuals receiving solid organ transplantation who are at risk of post-transplant diabetes mellitus. However, larger studies are needed to confirm these preliminary results. CGM-derived data are not currently validated for the diagnosis of diabetes. There is no CGM-derived definition of normoglycaemia in people without diabetes. Looking to the future, CGM metrics, in tandem with physical activity, dietary intake, and clinical parameters, and eventually bioinformatics, may inform personalised risk scores for precision prevention of individuals at risk. We conclude that further research is needed to clarify the indications, drawbacks, and feasibility of CGM use in people at high risk of diabetes to identify those groups who could benefit most from this technology. Full article

The lung is increasingly recognized as an organ with dual endocrine and respiratory roles, participating in a complex bidirectional crosstalk with systemic hormones and local/paracrine activity. Endocrine and paracrine pathways regulate lung development, ventilation, immunity, and repair, while pulmonary cells express hormone receptors and secrete mediators with both local and systemic effects, defining the concept of the “endocrine lung”. This narrative review summarizes current evidence on the endocrine–pulmonary axis. Thyroid hormones, glucocorticoids, sex steroids, and metabolic hormones (e.g., insulin, leptin, adiponectin) critically influence alveologenesis, surfactant production, ventilatory drive, airway mechanics, and immune responses. Conversely, the lung produces mediators such as serotonin, calcitonin gene-related peptide, endothelin-1, leptin, and keratinocyte growth factor, which regulate vascular tone, alveolar homeostasis, and immune modulation. We also describe the respiratory manifestations of major endocrine diseases, including obstructive sleep apnea and lung volume alterations in acromegaly, immunosuppression and myopathy in Cushing’s syndrome, hypoventilation in hypothyroidism, restrictive “diabetic lung”, and obesity-related phenotypes. In parallel, chronic pulmonary diseases such as chronic obstructive pulmonary disease, interstitial lung disease, and sleep apnea profoundly affect endocrine axes, promoting insulin resistance, hypogonadism, GH/IGF-1 suppression, and bone metabolism alterations. Pulmonary neuroendocrine tumors further highlight the interface, frequently presenting with paraneoplastic endocrine syndromes. Finally, therapeutic interactions are discussed, including the risks of hypothalamic–pituitary–adrenal axis suppression with inhaled corticosteroids, immunotherapy-induced endocrinopathies, and inhaled insulin. Future perspectives emphasize mapping pulmonary hormone networks, endocrine phenotyping of chronic respiratory diseases, and developing hormone-based interventions. Full article

Background: Polycystic ovarian syndrome (PCOS) is a common female endocrinopathy, but its interrelations with arterial hypertension (AH) are still debatable. Therefore, the present study aims to explore the risk factors for hypertension in a large group of well-phenotyped women with PCOS. Methods: The data of 1047 Bulgarian PCOS patients diagnosed according to Rotterdam criteria in the period 2005–2022 were studied retrospectively. The risk factors for hypertension were estimated in the PCOS women with different phenotypes. Results: The prevalence of AH was 17.6% among the PCOS women, with 4.2% of them being on antihypertensive treatment. The AH prevalence was increased in women with the “classic” phenotype compared to others (18.9% vs. 12.9%, p = 0.037). The most important risk factors associated with hypertension were the presence of diabetes mellitus type 2 (DMT2), obesity, family history of AH, and age ≥ 30 years (p < 0.001). The prevalence of impaired glucose tolerance (IGT) but not impaired fasting glucose was also related to the development of AH. Conclusions: The leading independent factors associated with hypertension in PCOS patients are the presence of DMT2, IGT, obesity, family history of hypertension, and age, but not the degree of hyperandrogenism. Population-based studies, including distinct ethnic groups, are needed to reveal the pathophysiology and the optimal clinical management of AH in PCOS. Full article

Background/Objectives: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy experienced by females. Diagnosis of PCOS is established when at least two of the following are present: hyperandrogenism, oligo-anovulation, and/or polycystic ovaries. Conservative treatment for PCOS includes dietary modifications and physical activity. The purpose of this scoping review was to evaluate the efficacy of a ketogenic diet in improving biochemical measures and reducing the severity of PCOS symptoms. Methods: CINAHL, PubMed, and Google Scholar databases were searched to find research published in peer-reviewed journals between 2019 and 2025. An article was included in this scoping review if the study assessed the effectiveness of a ketogenic diet on improving the signs and symptoms in patients with PCOS. Results: Eight studies met the inclusion criteria. Weight loss was achieved by subjects who adopted a very low-calorie ketogenic diet (VLCKD), low-calorie ketogenic diet (LCKD), classic ketogenic diet (CKD), or a Mediterranean eucaloric ketogenic diet (KEMEPHY). Patients with PCOS who consumed a ketogenic diet experienced improved biochemical measures, including androgen levels, lipid levels, HOMA-IR, blood glucose, insulin, LH/FSH ratio, DHEAS, SHBG, AFC, and AMH. A ketogenic diet was also associated with improvements in menstruation, fertility, and OHSS. Conclusions: Adopting a short-term ketogenic diet may have positive health benefits for patients with PCOS. Full article

Background/Objectives: McCune–Albright syndrome (MAS) is a rare disease characterized by the triad of fibrous dysplasia (FD), café au lait skin macules, and hyperfunctioning endocrinopathies. Although there are many case reports of MAS, few have discussed long-term oral management. We describe the long-term follow-up of an MAS patient over 15 years. Case Presentation: A male patient aged 13 years and 7 months was referred to our department with a chief complaint of difficulty with toothbrushing. He was diagnosed with MAS at 9 years, and bisphosphonate therapy was started. We continued to review the patient periodically and extracted several primary teeth with no adverse effects such as the medication-related osteonecrosis of the jaw (MRONJ). We evaluated the changes in FD using facial photographs, and facial asymmetry worsened over time until the age of 19, when surgery was performed. Although improvement was observed after surgery, there was a tendency for recurrence up to the age of 25 years. Conclusions: Continuous dental support over 15 years has prevented oral disease and minimized the need for surgical procedures such as tooth extractions, which are factors in MRONJ. The worsening of FD on the left side caused facial asymmetry until the age of 25 years; however, the asymmetry may have stabilized with the development of FD on the right side and with age-related changes. It is important for dental professionals to provide MAS patients with appropriate oral health instruction and oral management, taking changes in FD into consideration. Full article

Maternal health has a profound impact on fetal development, influencing the risk of pediatric endocrine disorders both directly and indirectly through various biological and environmental mechanisms. Throughout pregnancy, several endocrine disorders can arise or be exacerbated due to the physiological changes that occur. An in-depth review of articles with evidence-based research discussing the significant effects of maternal endocrinopathies and endocrine disruptors on fetal development and infant health was conducted in this review paper. The most common endocrine disorder during pregnancy is gestational diabetes mellitus, which has an incidence rate of 2–16%, depending on ethnic origin. Maternal diabetes, apart from macrosomia and hypoglycemia, increases the risk for several pregnancy and neonatal complications such as stillbirth, perinatal mortality, and congenital malformations. Other endocrine issues occurring in pregnancy include alterations in thyroid hormone levels, obesity-related insulin resistance, Cushing syndrome, or polycystic ovarian syndrome, which all may negatively influence the fetus, as well as offspring development. Additionally, environmental exposure to harmful substances during pregnancy can disrupt endocrine function. Bisphenol A is the most common endocrine disruptor, which is particularly detrimental during gestation. Bisphenol A exposure is related to low birth weight, preterm birth, or developmental delays. Also, its exposition could be associated with an increased risk of obesity, metabolic disorders, and certain cancers later in life. Endocrinopathies and exposure to endocrine disruptors during pregnancy represent a challenging problem, being widespread and demanding appropriate management to reduce fetal and newborn complications. Full article