PURPOSE: Gestational diabetes mellitus (GDM) is a common metabolic disorder of pregnancy associated with placental dysfunction and adverse maternal-fetal outcomes. LncRNAs have emerged as important regulators in metaboli...PURPOSE: Gestational diabetes mellitus (GDM) is a common metabolic disorder of pregnancy associated with placental dysfunction and adverse maternal-fetal outcomes. LncRNAs have emerged as important regulators in metabolic diseases. The clinical significance and molecular mechanisms of lncRNA PANDAR in GDM remain unclear. METHODS: 117 GDM patients and 110 healthy pregnant women were enrolled. Relative expression of genes was measured by qRT-PCR. The diagnostic value of PANDAR was assessed using ROC analysis, and its association with adverse pregnancy outcomes was evaluated by logistic regression. High-glucose model was established in HTR-8/Svneo trophoblast cells to investigate the function of PANDAR. Cell apoptosis, viability, and invasion were assessed using flow cytometry, CCK-8, and Transwell assays. The regulatory relationships among molecules were validated by dual-luciferase reporter assays. RESULTS: PANDAR expression was upregulated in GDM patients and exhibited good diagnostic performance. PANDAR levels were higher in GDM patients with adverse pregnancy outcomes. Elevated PANDAR was independently associated factor for adverse pregnancy outcomes. High glucose induced PANDAR expression and promoted trophoblast apoptosis while inhibiting cell viability and invasion, effects that were alleviated by PANDAR silencing. PANDAR functioned as a ceRNA for miR-192-5p, thereby upregulating the pro-apoptotic target BCL2L11. Rescue experiments confirmed that a PANDAR/miR-192-5p/BCL2L11 axis mediated trophoblast dysfunction under hyperglycemic conditions. CONCLUSION: PANDAR is associated with adverse pregnancy outcomes and may reflect hyperglycemia-induced cellular responses by promoting trophoblast dysfunction via a miR-192-5p/BCL2L11 axis.
PURPOSE: Obesity that develops at different life stages may have distinct metabolic consequences, and the mechanisms distinguishing juvenile from adult-onset obesity remain incompletely defined. Thus, we examined how the...PURPOSE: Obesity that develops at different life stages may have distinct metabolic consequences, and the mechanisms distinguishing juvenile from adult-onset obesity remain incompletely defined. Thus, we examined how the timing of exposure to a high-fat diet (HFD) affects expansion, lipid metabolism, and insulin signaling in epididymal visceral adipose tissue (eVAT). METHODS: Male C57BL/6J mice were fed either a control diet or a 60% HFD, initiated immediately after weaning during the juvenile period (3 weeks of age) or at young adulthood (9 weeks of age), and continued until 17 weeks of age. RESULTS: HFD increased both total VAT and subcutaneous adipose tissue (SAT) mass regardless of exposure timing. However, when introduced during adulthood, it led to a higher total VAT to SAT ratio, greater total VAT mass, more severe hyperglycemia, and more pronounced eVAT adipocyte hypertrophy and reduction in PPARγ protein levels. Only adult mice exposed to HFD exhibited impaired eVAT insulin signaling, characterized by increased inhibitory IRS1 phosphorylation, reduced Akt phosphorylation, and lower GLUT4 protein levels. This was associated with increased fatty acid influx, indicated by higher lipoprotein lipase and Cd36 expression, reduced SREBP-1c protein levels, and a shift toward a pro-lipolytic profile with increased Hsl expression. CONCLUSION: These findings indicate that adult exposure to HFD leads to more adverse effects on eVAT expansion, lipid metabolism, and insulin signaling than juvenile exposure, further supporting the concept that the developmental stage at which caloric overload is initiated shapes adipose tissue plasticity and influences the severity of obesity-related metabolic disturbances.
BACKGROUND: Type 2 diabetes mellitus (T2DM) is a multifactorial metabolic disorder characterized by insulin resistance, dyslipidemia and inflammation. Although probiotics have shown potential in improving glycemic contro...BACKGROUND: Type 2 diabetes mellitus (T2DM) is a multifactorial metabolic disorder characterized by insulin resistance, dyslipidemia and inflammation. Although probiotics have shown potential in improving glycemic control in T2DM, the systemic mechanisms underlying their therapeutic effects remain largely unclear. METHODS: A high glucose-induced insulin-resistant zebrafish model was established to explore the interventional effects of Lactobacillus gasseri GDMCC AM63 (L. gasseri). Biochemical assays combined with untargeted metabolomics were used to comprehensively evaluate the efficacy of L. gasseri intervention. RESULTS: L. gasseri intervention significantly reduced fasting blood glucose levels, inhibited the expression of pro-inflammatory cytokines (tnfα and il-6), and upregulated the anti-inflammatory cytokine il-10. Metabolomic profiling identified 210 shared annotated DAMs in pairwise comparisons (T2DM_vs_control (Ctrl) group, and L. gasseri intervention (LG)_vs_T2DM group), which were mainly involved in lipid, amino acid, and carbohydrate metabolism. Pathway enrichment analysis showed significant enrichment of glycerophospholipid, fructose-mannose, pentose phosphate, riboflavin, and linoleic acid metabolic pathways. After FDR correction, 27 shared annotated significant DAMs (SDAMs) were identified. Integrated metabolomics and network pharmacology analysis suggested that L. gasseri may exert a therapeutic effect on T2DM by indirectly regulating signaling pathways such as PI3K/Akt and JAK/STAT. Randomforest analysis highlighted 18R-Hepe and Azii as potential metabolic biomarkers with predictive value. CONCLUSION: This study systematically investigated the metabolic regulatory mechanisms by which L. gasseri ameliorates T2DM, providing experimental evidence to support its potential as an effective interventional strategy for improving insulin resistance and related metabolic dysfunctions.
PURPOSE: Exogenous Cushing's syndrome (CS) is most commonly caused by therapeutic glucocorticoids (GC), but rare and atypical sources can mimic endogenous GC. This narrative review provides a concise overview of these un...PURPOSE: Exogenous Cushing's syndrome (CS) is most commonly caused by therapeutic glucocorticoids (GC), but rare and atypical sources can mimic endogenous GC. This narrative review provides a concise overview of these uncommon causes and their diagnostic implications. METHODS: A PubMed search was performed using the keywords "Cushing syndrome," "factitious Cushing syndrome," "herbal medicine", "supplements" and "endocrine disruption" on March 9th, 2026. Additional articles were identified through manual screening of reference lists. No restrictions were applied regarding language or study design, and the most relevant publications were selected. RESULTS: Three main categories of rare exogenous CS were identified. First, herbal or traditional remedies adulterated with undeclared GC. Second, compounds with GC-like activity, which activate the glucocorticoid receptor and suppress the hypothalamic-pituitary-adrenal axis. Third, factitious CS due to covert GC self-administration, often associated with psychiatric or caregiver-fabricated conditions. Diagnosis can be challenging; advanced analytical methods, including liquid chromatography-tandem mass spectrometry (LC-MS/MS) and liquid chromatography-high resolution mass spectrometry (LC-HRMS), are essential to detect synthetic or undeclared GC and differentiate these cases from endogenous hypercortisolism. CONCLUSION: Rare exogenous causes of CS represent important diagnostic challenges. Careful evaluation of patient history, combined with the use of LC-MS/MS or LC-HRMS, is crucial to identify these conditions, prevent misdiagnosis, and avoid unnecessary diagnostic or surgical interventions.
PURPOSE: Traditional markers such as HbA1c and BMI are commonly used to assess metabolic risk in adolescents with type 1 diabetes mellitus (T1DM), but novel biomarkers like the triglyceride-glucose (TyG) index and phase...PURPOSE: Traditional markers such as HbA1c and BMI are commonly used to assess metabolic risk in adolescents with type 1 diabetes mellitus (T1DM), but novel biomarkers like the triglyceride-glucose (TyG) index and phase angle (PA) may provide a more comprehensive evaluation of metabolic risk. However, their potential role in this population remains unclear. We aimed (1) to evaluate the association of the TyG index and PA with glycemic control, cardiovascular risk and body composition in adolescents with T1DM, and (2) to determine optimal cut-off points for these biomarkers to predict metabolic risk. METHODS: Seventy-three adolescents (46.6% female, 10-19 years) with T1DM from two hospitals were included in this cross-sectional study. Sociodemographic, bioelectrical impedance (BIA) and clinical data were collected during routine visits. The TyG index was calculated from fasting triglyceride and glucose levels, and PA was measured via BIA. Correlations were analyzed using Pearson or Spearman coefficients, and ROC curve analyses were used to determine optimal cut-off points. RESULTS: PA correlated positively with skeletal muscle and fat-free mass and inversely with cardiovascular risk indicators. TyG was strongly associated with adiposity, glycemic variability and cardiovascular risk markers. A preliminary TyG threshold of 8.09 was identified, while no PA cut-off could be established. CONCLUSIONS: PA and the TyG index are promising, non-invasive biomarkers that complement traditional measures in assessing metabolic risk in adolescents with T1DM. Integrating these biomarkers into routine evaluation may enhance early risk detection and support holistic management in this population. TRIAL REGISTRATION NUMBER: NCT07021326.
PURPOSE: Type 1 diabetes mellitus (T1DM) results from autoimmune-mediated destruction of pancreatic β-cells, leading to absolute insulin deficiency. Current treatments rely on insulin replacement and do not prevent β-cel...PURPOSE: Type 1 diabetes mellitus (T1DM) results from autoimmune-mediated destruction of pancreatic β-cells, leading to absolute insulin deficiency. Current treatments rely on insulin replacement and do not prevent β-cell loss. 4-Methylumbelliferone (4-MU), an inhibitor of hyaluronan synthesis, has shown anti-inflammatory and cytoprotective effects, but its therapeutic potential and mechanisms in T1DM remain unclear. METHODS: A streptozotocin (STZ)-induced mouse model of T1DM was treated with 4-MU for three weeks. Blood glucose levels and glucose tolerance were evaluated. Pancreatic islet morphology and cell composition were assessed by immunofluorescence. In parallel, STZ -injured MIN6 and βTC6 β-cells were used to investigate the effects of 4-MU on cell viability, oxidative stress, intracellular Ca²⁺ homeostasis, and glucose-stimulated insulin secretion. Network pharmacology, molecular docking, qPCR, and Western blot analyses were conducted to explore the underlying mechanisms. RESULTS: 4-MU significantly reduced hyperglycemia and improved glucose tolerance in T1DM mice, accompanied by preservation of β-cell mass, normalization of the β/α-cell ratio, and reduced islet inflammation. In vitro, 4-MU protected β-cells from STZ-induced injury by decreasing reactive oxygen species (ROS) accumulation, restoring intracellular Ca²⁺ balance, and improving insulin secretion. Network pharmacology identified 48 shared targets between 4-MU and T1DM, with KEGG pathway enrichment highlighting the PI3K/Akt signaling pathway. Molecular docking revealed stable binding of 4-MU to key regulators, including EGFR, Akt, ESR1, INSR, and IGF1R. Consistently, 4-MU enhanced the phosphorylation of EGFR, PI3K, and Akt in injured β-cells. CONCLUSION: 4-MU exerts protective effects in T1DM by preserving pancreatic β-cells survival and function, potentially through activation of the EGFR/PI3K/Akt signaling pathway.
BACKGROUND: The cardiovascular safety of testosterone replacement therapy (TRT) in older men with hypogonadism has been debated for over a decade, largely on the basis of underpowered trials and conflicting observational...BACKGROUND: The cardiovascular safety of testosterone replacement therapy (TRT) in older men with hypogonadism has been debated for over a decade, largely on the basis of underpowered trials and conflicting observational data. The TRAVERSE trial, published in 2023, provided the first adequately powered, placebo-controlled evidence on this question. OBJECTIVES: This review synthesises current evidence on the cardiovascular safety of TRT in older men, with particular attention to the interpretation of TRAVERSE findings, the clinical significance of non-MACE safety signals, and the practical management of organic versus functional hypogonadism. METHODS: A systematic search of PubMed/MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) was conducted through March 2026. Approximately 450 articles were identified; 64 met the inclusion criteria and were selected for review. Evidence was appraised according to study design, with RCTs and meta-analyses weighted above observational data. RESULTS: TRAVERSE demonstrated non-inferiority of TRT versus placebo for major adverse cardiovascular events (MACE) in men with confirmed hypogonadism and elevated cardiovascular risk (HR 0.96, 95% CI 0.78-1.17) [5]. Non-MACE signals - including atrial fibrillation (3.1% vs. 2.4%), pulmonary embolism (2.0% vs. 1.5%), and acute kidney injury (2.3% vs. 1.5%) - were numerically higher in the TRT arm but did not reach statistical significance within the trial. In contrast, large observational cohorts consistently report statistically significant associations between TRT and AF and VTE. Erythrocytosis was the most reproducible adverse effect (17.0% vs. 3.3%, p < 0.001). Functional hypogonadism secondary to obesity or metabolic syndrome responds to lifestyle intervention and GLP-1/GIP agonists, with testosterone normalisation in 81.4% at 6 months and 89.5% at 24 months after bariatric surgery [45]. CONCLUSIONS: TRT does not increase MACE risk in men with confirmed organic hypogonadism when titrated to physiological levels. Non-MACE signals warrant vigilance rather than contraindication. Metabolic optimisation should precede TRT in functional hypogonadism. Individualised monitoring and careful patient selection remain essential.
Arcidiacono GP, Torres MO, Ceolin C
… +24 more, Tripepi G, Camozzi V, Bertocco A, Peleg Falb M, Diogo M, Guidolin F, Cecchinato A, Voltan G, Ferrarese M, Rodà MG, Pala E, Angelini A, Boemo DG, Nesoti MV, Campello E, Ruggieri P, Fusaro M, Minisola S, Simioni P, Sergi G, Giannini S, De Rui M, Sella S, Hip-POS working group
PURPOSE: Vitamin D deficiency (VDD) is common in older adults with osteoporosis, but its prevalence, determinants, and clinical impact in hip fracture (HF) patients remain incompletely defined. This study investigated th...PURPOSE: Vitamin D deficiency (VDD) is common in older adults with osteoporosis, but its prevalence, determinants, and clinical impact in hip fracture (HF) patients remain incompletely defined. This study investigated the prevalence of VDD, associated factors, and 12-month outcomes in HF patients managed within a Fracture Liaison Service program. METHODS: In this prospective cohort study, 934 patients hospitalized for HF were enrolled between March 2023 and March 2025. VDD was defined as serum 25-hydroxyvitamin D [25-(OH)D] < 50 nmol/L. Clinical characteristics, laboratory parameters, and 12-month outcomes were assessed. RESULTS: Overall VDD prevalence was 53.6%, with a median 25-(OH)D concentration of 22 nmol/L among deficient patients. Independent predictors of VDD were male sex (p < 0.001), diabetes mellitus (p = 0.003), dementia (p = 0.013), and active smoking (p = 0.045), while prior vitamin D supplementation was negatively associated (p < 0.001). Decision tree analysis showed VDD prevalence ranging from 17.2% to 86.3% across patient phenotypes. Patients with VDD showed higher levels of bone turnover markers. In unadjusted analyses, VDD was associated with higher 12-month mortality (HR 1.65, 95% CI 1.12-2.42, p = 0.010), an association attenuated and no longer significant after adjustment for age, sex, and comorbidity burden (HR 1.31, 95% CI 0.88-1.96, p = 0.188). No associations were observed between VDD and rehospitalization or refracture rates. CONCLUSION: VDD is highly prevalent in HF patients. Although associated with higher mortality in unadjusted analyses, this relationship appears largely explained by comorbidity burden. These findings highlight the importance of recognizing VDD and implementing targeted vitamin D supplementation strategies in high-risk HF populations.
PURPOSE: The aim of this study was to evaluate the relationship between late onset hypogonadism (LOH) with inflammation and lower-limb vascular complications in men with type 2 diabetes (T2D). METHODS: This single-centre...PURPOSE: The aim of this study was to evaluate the relationship between late onset hypogonadism (LOH) with inflammation and lower-limb vascular complications in men with type 2 diabetes (T2D). METHODS: This single-centre, retrospective observational study included men with T2D who underwent hormonal evaluation between 2020 and 2024. LOH was diagnosed according to SIAMS/SIE and EAU guidelines and participants were classified as hypogonadal or eugonadal. Demographic, metabolic, inflammatory, and haematological parameters were collected. Lower-limb vascular complications, including peripheral artery disease (PAD), diabetic foot ulcer (DFU), osteomyelitis and amputation, were assessed. Logistic regression analyses were performed to evaluate the association between testosterone (T) levels and vascular complications. RESULTS: The study population included 155 men, with a prevalence of LOH of 50.3%. Hypogonadal men showed significantly lower haemoglobin and haematocrit levels and higher inflammatory markers compared with eugonadal subjects. Microvascular complications did not differ between groups, except for a higher prevalence of DFU in hypogonadal men. Conversely, macrovascular lower-limb complications were more frequent in men with LOH, including PAD, osteomyelitis, and amputation. Higher T levels were associated with a reduced number of these outcomes. After multivariable adjustment, T levels remained independently associated with the risk of PAD and lower limb amputation. CONCLUSION: In our cohort of men with T2D, hypogonadism is associated with an increased burden of macrovascular and lower limb complications. Lower T levels were independently associated with PAD and amputation, supporting hypogonadism as a marker of vascular impairment.
PURPOSE: Diabetic ketoacidosis (DKA) stands as the most common acute hyperglycaemic complication in children with type 1 diabetes (T1D) and remains associated with considerable morbidity and mortality. Although gut dysbi...PURPOSE: Diabetic ketoacidosis (DKA) stands as the most common acute hyperglycaemic complication in children with type 1 diabetes (T1D) and remains associated with considerable morbidity and mortality. Although gut dysbiosis has been reported in newly diagnosed T1D, the gut microbiota and microbial metabolites during DKA onset remain poorly characterized. METHODS: Shotgun metagenomic sequencing was performed on fecal samples from 96 newly diagnosed T1D children, including 32 presenting with DKA upon admission. Short-chain fatty acids (SCFAs) were quantified using gas chromatography/mass spectrometry (GC/MS). Comparative and correlation analyses were conducted to explore differences in gut microbial composition, SCFA levels, and their association with clinical indicators of DKA severity. RESULTS: Children with DKA exhibited distinct gut microbial compositions, with marked β-diversity separation from non-DKA individuals. The DKA group was characterized by an enrichment of potential pathogens and a significant depletion of SCFA-producing genera, including Anaerobutyricum, Dialister, Ruminococcus, Roseburia, Dorea, and Butyricicoccus. Correspondingly, fecal SCFA levels were significantly reduced in the DKA group. Moreover, SCFAs and their producing bacteria were strongly correlated with clinical indices of DKA severity. Mediation analysis suggested that reductions in SCFAs, particularly propionic acid and butyric acid, were associated with metabolic alterations linking SCFA-producing bacteria to DKA. CONCLUSION: This study provides a comprehensive characterization of gut microbiota and SCFA alterations in T1D children at DKA onset. The depletion of SCFA-producing bacteria and their metabolites reflects metabolic disturbances associated with DKA, and highlights SCFAs and their producers as candidate metabolic features warranting further validation as biomarkers and therapeutic targets.
PURPOSE: Adrenocortical carcinoma (ACC) is a rare tumor with highly aggressive malignancy. Its two main pathological subtypes, conventional ACC (CAC) and oncocytic ACC (OAC), are hypothesized to differ in clinical behavi...PURPOSE: Adrenocortical carcinoma (ACC) is a rare tumor with highly aggressive malignancy. Its two main pathological subtypes, conventional ACC (CAC) and oncocytic ACC (OAC), are hypothesized to differ in clinical behavior, but comparative studies are limited due to the rarity of OAC. This study aimed to compare the clinical characteristics, pathological features, and prognosis between CAC and OAC. METHODS: A retrospective review was conducted on 128 ACC patients (105 CAC, 23 OAC) during the period of October 2015 and October 2025. Data on clinical presentation, hormonal status, pathological findings, and survival outcomes were collected and analyzed. Statistical comparisons were performed using t-tests, Mann-Whitney U tests, chi-square tests, Cox proportional hazards regression analysis, multivariable Cox proportional hazards regression analysis, and Kaplan-Meier survival analysis with log-rank test. RESULTS: Compared with CAC, OAC patients had a significantly lower prevalence of Cushing's syndrome (13.0% vs. 39.0%, P < 0.05) and hypertension (17.4% vs. 48.6%, P < 0.01). In contrast, adrenal-derived sexual characteristics abnormalities were more common in OAC (65.2% vs. 26.0%, P < 0.001). Pathologically, compared with CAC, the Ki-67 index was significantly lower in OAC (median: 14% vs. 20%, P < 0.05). Also, Kaplan-Meier survival analysis revealed a more favorable overall survival(OS) for OAC, with a 5-year OS rate of 70.4% compared to 48.4% for CAC (P < 0.05). After multivariate adjustment for ENSAT stage and Ki‑67, pathological subtype lost independent prognostic significance, while ENSAT stage and Ki‑67 remained independent predictors. CONCLUSIONS: CAC was associated with a higher frequency of glucocorticoid excess symptom, a higher proliferative index (Ki-67). OAC was characterized by a higher prevalence of androgen excess symptoms. OAC demonstrated similar OS to CAC after adjustment for ENSAT stage and Ki‑67.
PURPOSE: To define an age-continuous reference range for testosterone (T) in females. METHODS: A large-scale retrospective analysis of anonymised serum T collected via capillary sampling from a private healthcare service...PURPOSE: To define an age-continuous reference range for testosterone (T) in females. METHODS: A large-scale retrospective analysis of anonymised serum T collected via capillary sampling from a private healthcare service. 5,323 female individuals (19-59 years) with no history of reproductive conditions, normal BMI and regular cycles were analysed to establish a robust, age-continuous reference range for T, including probability density distributions and specific quantiles. Competing models of log T values as a function of age were statistically assessed, and the best model selected. Additionally, a cohort with self-reported hirsutism was compared. RESULTS: A weakly skew-Normal distribution describes the best-fit distribution of log T values at any specific age, such that the mean decreases and the variance increases linearly with age. Analysis of the hirsutism cohort showed significantly higher T levels compared to the reference cohort. CONCLUSION: Establishing a reliable reference range for female T enables clinicians to differentiate between physiological and pathological states (e.g. hyperandrogenism). Here, we establish a robust, age-continuous reference range for T in a large female population under strict inclusion criteria. The findings underscore the importance of age-specific reference ranges and highlight a substantial decrease in T over adult life. This study provides a valuable tool for clinicians and researchers seeking to compare patient hormone levels to a reliable reference distribution of T levels in women.
Baroncelli GI, Tessaris D, Aversa T
… +19 more, Bertelli E, Comberiati P, Corica D, Di Iorgi N, Faienza MF, Fintini D, Franceschi R, Grandone A, Karapurackal MA, Longhi S, Pitea M, Secco A, Trifirò G, Ubertini G, Urbano F, Vierucci F, Wasniewska M, Mora S, de Sanctis L
PURPOSE: Children and adolescents frequently experience fractures related to accidental injuries; however, fractures may also result from non-accidental trauma in abused children or from underlying bone fragility due to...PURPOSE: Children and adolescents frequently experience fractures related to accidental injuries; however, fractures may also result from non-accidental trauma in abused children or from underlying bone fragility due to primary or secondary osteoporosis. In pediatric patients with fragility fractures diagnosis and treatment may be delayed. This document aims to provide clinicians with a practical approach to the diagnosis and management of fragility fractures in children and adolescents. METHODS: Between November 2024 and June 2025, a group of Italian pediatric endocrinologists with expertise in bone and mineral metabolism held regular online meetings to discuss key issues related to the diagnosis and management of pediatric bone fragility and developed experts opinion statements based on clinical experience and a review of the relevant literature. RESULTS: The expert panel formulated consensus statements on the clinical management of children and adolescents with fragility fractures. Seven main areas were addressed: 1) definition of fragility fractures and pediatric osteoporosis; 2) diagnostic approach; 3) main causes of primary and secondary osteoporosis; 4) assessment of the potential for spontaneous recovery from bone fragility; 5) management of bisphosphonate therapy; 6) other therapeutic options; 7) conservative measures. CONCLUSION: The diagnosis of osteoporosis in pediatric patients should follow a clinically oriented approach. Genetic testing plays a crucial role in identifying primary forms of osteoporosis. Vertebral reshaping may occur in some patients with secondary osteoporosis. Bisphosphonates represent the mainstay of treatment in children and adolescents with bone fragility. Conservative measures aimed at optimizing bone strength may be beneficial in selected cases.
BACKGROUND: Premature pubarche (PP), defined as the early onset of pubic hair and often associated with mild androgen excess, is a common reason for referral to a pediatric endocrinologist. A small proportion of cases ma...BACKGROUND: Premature pubarche (PP), defined as the early onset of pubic hair and often associated with mild androgen excess, is a common reason for referral to a pediatric endocrinologist. A small proportion of cases may progress to central precocious puberty (CPP). Data on the factors determining pubertal tempo and associated growth outcomes in these individuals are limited. OBJECTIVE: To identify predictors of pubertal progression and final height (FH) in girls with PP and to evaluate growth outcomes in those progressing to CPP. DESIGN-METHODS: We retrospectively analyzed 88 girls with PP who attained FH; 13 progressed to CPP (PP-to-CPP). Auxological data, bone age (BA), pubertal development, and plasma androgen profiles were evaluated. RESULTS: At presentation, corrected height SDS (CH-SDS) in girls with PP correlated with BA-SDS and BA/chronological age (BA/CA) ratio (p=0.03 and p=0.007). Corrected FH-SDS was positively associated with baseline CH-SDS in both PP and PP-to-CPP groups (p<0.001 and p=0.0002). Compared with PP, the PP-to-CPP group had higher baseline CH-SDS, BA-SDS and BA/CA ratio (all p=0.02). Baseline CH-SDS was the strongest independent predictor of corrected FH-SDS (p<0.001), while BMI-SDS showed a negative association (p=0.003). Baseline dehydroepiandrosterone-sulfate (DHEA-S) was not associated with CH-SDS, BA advancement, progression to CPP, or corrected FH-SDS in either group. Receiver operating characteristic (ROC) analyses for progression to CPP identified a BA/CA cutoff of 1.2; and a CH-SDS cutoff of 1.8 (p=0.01). CONCLUSION: Growth relative to genetic potential and skeletal maturation at presentation were the strongest predictors of progression to CPP and FH outcomes in girls with PP. Although DHEA-S reflects adrenal maturation and early androgen exposure, baseline DHEA-S concentrations were not associated with progression to CPP or long-term growth outcomes in our cohort.
PURPOSE: This study investigated whether breastfeeding (BF) is associated with a reduction in persistent hypertension (PH) and glucose metabolism impairment in patients with polycystic ovary syndrome (PCOS) who experienc...PURPOSE: This study investigated whether breastfeeding (BF) is associated with a reduction in persistent hypertension (PH) and glucose metabolism impairment in patients with polycystic ovary syndrome (PCOS) who experienced pregnancy-induced hypertension (PIH) and/or gestational diabetes mellitus (GDM). METHODS: This secondary observational analysis utilized data from two prospective cohort studies involving 241 participants (101 PCOS patients; 140 controls) with a history of GDM and/or PIH. At 18 months post-delivery, patients underwent physical examinations, blood pressure monitoring, and biochemical assays, including oral glucose tolerance tests. Feeding practices were categorized as exclusive BF, partial BF, or formula feeding (FF). RESULTS: Patients with PCOS demonstrated significantly shorter BF durations (9.6 ± 7.0 vs. 12.6 ± 5.9 months; P < 0.001) and lower exclusive BF rates (39.6% vs. 62.9%; P < 0.001) compared to controls. At 18 months, the composite cardiometabolic outcome prevalence was 55.4% in the PCOS group versus 11.4% in controls (P < 0.001). Multivariate analysis identified exclusive BF as a potent independent factor associated with a significantly lower risk (adjusted OR 0.14, 95% CI 0.05-0.38; P < 0.001) of cardiometabolic impairment. CONCLUSION: Breastfeeding is associated with a significant reduction in long-term cardiometabolic risks in women with PCOS following complicated pregnancies. Supporting and optimizing lactation may represent a valuable non-pharmacological strategy to consider for this high-risk population.
Demarchis L, Chiloiro S, Mattogno PP
… +17 more, Cicchinelli M, Giambò P, Valeri F, Panizzi E, Angelini F, Giampietro A, Vodola E, Milardi D, D'Alessandris GQ, De Marinis L, Lauretti L, Rigante M, Bianchi A, Urbani A, Pontecorvi A, Doglietto F, Iavarone F
INTRODUCTION: Bone metabolism is typically impaired in patients with acromegaly due to increased bone turnover, increased bone resorption, and impaired bone neoformation. The pathogenetic mechanisms underlying skeletal f...INTRODUCTION: Bone metabolism is typically impaired in patients with acromegaly due to increased bone turnover, increased bone resorption, and impaired bone neoformation. The pathogenetic mechanisms underlying skeletal fragility in patients with acromegaly remain not fully clarified. We aim to compare the bone proteome of patients with acromegaly to that of a control group of patients with non-secreting pituitary tumors (NSPTs). METHODS: A Liquid Chromatography-Mass Spectrometry was conducted on ethmoid samples (after processing and digestion of the sample) of five patients with acromegaly and five patients with NSPTs, to identify and assay the proteome. Biological functions were investigated for proteins that were found quantitatively up- and down-regulated in the bone of acromegalic patients, with a ratio of variation based on Fold-Change (FC) >|1.50| and statistical significance (p-value < 0.05). RESULTS: 312 proteins belonging to each group were identified. Six proteins with positive FC (up-regulated) and 12 proteins with negative FC (down-regulated) significantly differ in patients with acromegaly than in patients with NSPTs. Among up- and down-regulated proteins, profilin-1, isoform 5 of the periostin, apolipoprotein E, and caveolin-1 were known to be involved in bone metabolism. In our cohort, a positive correlation was detected between the profilin-1, the isoform 5 of the periostin, GH, and IGF-I levels; and a negative correlation was detected between caveolin-1 and serum GH and IGF-I levels, and with apolipoprotein E and serum IGF-I levels. CONCLUSION: Our results proved that the bone of patients with acromegaly is characterized by a specific proteomic profile, which is closely correlated to GH and IGF-I hypersecretion.
BACKGROUND: Hypothalamic obesity (HO) is a severe, often treatment-refractory complication after craniopharyngioma (CP) surgery. Setmelanotide, a melanocortin-4 receptor agonist (MC4R-A), offers a targeted therapeutic ap...BACKGROUND: Hypothalamic obesity (HO) is a severe, often treatment-refractory complication after craniopharyngioma (CP) surgery. Setmelanotide, a melanocortin-4 receptor agonist (MC4R-A), offers a targeted therapeutic approach, but real-world data are limited. METHODS: We performed a retrospective review of patients with post-CP HO treated with setmelanotide at our center, collecting clinical, metabolic, and treatment-related data. RESULTS: Three young adults with HO after surgery for CP were included. Treatment responses were variable: one patient discontinued setmelanotide after continued weight gain, while two experienced reductions in weight, BMI, waist circumference, triglycerides and insulin levels over 6-9 months. Adverse effects were mild and non-limiting. CONCLUSION: Setmelanotide may provide meaningful benefit for selected patients with severe, treatment-refractory HO after CP. Despite small sample size, this series supports further investigation of MC4R agonism as a targeted therapy for acquired HO.