Journal of Endocrinological Investigation最新文献

{"title":"Prevalence, predictors, and clinical impact of vitamin D deficiency on 12-month outcomes in hip fracture patients.","authors":"Gaetano Paride Arcidiacono, Marco Onofrio Torres, Chiara Ceolin, Giovanni Tripepi, Valentina Camozzi, Anna Bertocco, Mor Peleg Falb, Martin Diogo, Francesca Guidolin, Alberta Cecchinato, Giacomo Voltan, Michela Ferrarese, Maria Grazia Rodà, Elisa Pala, Andrea Angelini, Deris Gianni Boemo, Maria Vittoria Nesoti, Elena Campello, Pietro Ruggieri, Maria Fusaro, Salvatore Minisola, Paolo Simioni, Giuseppe Sergi, Sandro Giannini, Marina De Rui, Stefania Sella","doi":"10.1007/s40618-026-02952-x","DOIUrl":"10.1007/s40618-026-02952-x","url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"2913-2924"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148340653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of breastfeeding on cardiometabolic risk in patients with polycystic ovary syndrome.","authors":"Stefano Palomba, Giuseppe Seminara, Flavia Costanzi, Rossella Cannarella, Tiziana Russo, Fabrizio Signore, Martina Sarica, Aldo E Calogero, Donatella Caserta, Antonio Aversa","doi":"10.1007/s40618-026-02948-7","DOIUrl":"10.1007/s40618-026-02948-7","url":null,"abstract":"<p><strong>Purpose: </strong>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).</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"2845-2854"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148296775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic profile of bone in patients with acromegaly: new insights from a pilot exploratory study.","authors":"Luigi Demarchis, Sabrina Chiloiro, Pier Paolo Mattogno, Michela Cicchinelli, Penelope Giambò, Federico Valeri, Elena Panizzi, Flavia Angelini, Antonella Giampietro, Emanuele Vodola, Domenico Milardi, Giorgio Quintino D'Alessandris, Laura De Marinis, Liverana Lauretti, Mario Rigante, Antonio Bianchi, Andrea Urbani, Alfredo Pontecorvi, Francesco Doglietto, Federica Iavarone","doi":"10.1007/s40618-026-02936-x","DOIUrl":"10.1007/s40618-026-02936-x","url":null,"abstract":"<p><strong>Introduction: </strong>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).</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"2709-2719"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148296814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rare causes of exogenous Cushing's Syndrome: a challenge for endocrinologists.","authors":"Valentino Marino Picciola, Margherita Medici, Maria Rosaria Ambrosio, Maria Chiara Zatelli","doi":"10.1007/s40618-026-02970-9","DOIUrl":"10.1007/s40618-026-02970-9","url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"2673-2678"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148347099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of the efficacy and safety of liraglutide, semaglutide, and tirzepatide for the treatment of overweight and obesity: a systematic review and network meta-analysis.","authors":"Wiktoria Pałka, Paweł Moćko, Katarzyna Śladowska, Przemysław Holko, Paweł Kawalec","doi":"10.1007/s40618-026-03006-y","DOIUrl":"10.1007/s40618-026-03006-y","url":null,"abstract":"<p><strong>Background/objectives: </strong>The rapid rise in overweight and obesity worldwide underscores the need for comparative evidence on long-term pharmacotherapy. The recent introduction of a 7.2 mg maintenance dose of semaglutide warrants particular attention. We assessed the efficacy and safety of glucagon-like peptide-1 (GLP-1) and GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists-liraglutide, semaglutide, and tirzepatide-focusing on the incremental value of semaglutide 7.2 mg.</p><p><strong>Subjects/methods: </strong>We conducted a systematic review and frequentist network meta-analysis (NMA) of phase 3 randomized controlled trials (RCTs) in adults (≥ 18 years) with body mass index (BMI) ≥ 25 kg/m², duration ≥ 52 weeks, comparing the above agents at approved weight management doses vs. placebo or each other (PROSPERO: CRD420251014401). Random effects models using the netmeta package estimated relative effects, ranking used P-scores.</p><p><strong>Results: </strong>Twenty-four RCTs were included in the analysis, of which 23 were eligible for inclusion in the NMA. All active treatments reduced body weight, waist circumference, and BMI vs. placebo. Tirzepatide 15 mg ranked highest for weight and waist reduction across analyses based on P-scores. Semaglutide 7.2 mg ranked above semaglutide 2.4 mg for all efficacy endpoints based on P-scores; but the significant advantage in percentage bodyweight change was found only in the diabetes subgroup. Liraglutide 3.0 mg yielded the smallest weight loss. No significant between treatment differences were observed for serious adverse events (SAEs); however, tirzepatide was associated with higher risk of injection site reactions, and liraglutide with higher risks of any AEs and discontinuation due to AEs. Considerable heterogeneity was present for efficacy outcomes, with limited evidence of networkwide inconsistency; safety networks showed low to moderate heterogeneity.</p><p><strong>Conclusions: </strong>GLP-1 and GLP-1/GIP receptor agonists produce clinically meaningful weight loss vs. placebo over ≥ 1 year. Semaglutide 7.2 mg consistently ranks above 2.4 mg, but the average incremental benefit (~ 2-3% points) appears modest and should be interpreted in the context of limited statistically significant differences between doses, as well as balanced against considerations of tolerability and patient preferences. Further head-to-head trials and real world studies are warranted to refine dose selection and long-term safety.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"2925-2938"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148680632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gouty tophi in Domenico Fetti's Archimedes: a clinico-iconographic analysis.","authors":"Amelian Madalin Bobu, Andrei Ionut Cucu, Raffaella Bianucci","doi":"10.1007/s40618-026-02867-7","DOIUrl":"10.1007/s40618-026-02867-7","url":null,"abstract":"","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"3101-3103"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147576022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between annual air pollutant exposure and thyroid function: a retrospective cross-sectional study.","authors":"Sinyoung Cho, Seo Eun Hwang, Jae Moon Yun, Soon Tae Kim, Yoon Hee Kang, Hyun-Jin Kim, Jin-Ho Park","doi":"10.1007/s40618-026-02965-6","DOIUrl":"10.1007/s40618-026-02965-6","url":null,"abstract":"<p><strong>Aims: </strong>Despite the high burden of air pollutants, the association between air pollutant exposures and thyroid function in the general population is inconclusive. This study aimed to investigate the association between annual exposure to air pollutants and thyroid function in Korean adults.</p><p><strong>Methods: </strong>This cross-sectional study included a total of 16,193 participants (8,812 males, 7,381 females; mean age: 53.8 ± 13.1 years) who underwent health examinations at Seoul National University and had thyroid-stimulating hormone (TSH) concentrations within the range of 0.1-10.0 mIU/L. The yearly average levels of five air pollutants, including particulate matter (PM_2.5 and PM₁₀), NO₂, SO₂, and CO, were estimated using the Community Multiscale Air Quality model. Multivariable linear and logistic regression models were used to examine the associations between annual ambient air pollutant exposures and thyroid function parameters, including TSH and free thyroxine (FT4).</p><p><strong>Results: </strong>Interquartile range (IQR) increases for PM_2.5, PM₁₀, NO₂, SO₂, and CO were positively associated with TSH and negatively associated with FT4 (all P < 0.001). Significant non-linear associations were observed for PM_2.5 and NO₂ with log-transformed TSH, whereas all air pollutants showed non-linear associations with log-transformed FT4. The IQR increases of all air pollutants showed positive associations with the highest quartile of TSH (high TSH) and the lowest quartile of FT4 (low FT4), respectively. When thyroid function was categorized into four groups based on high/low TSH and/or high/low FT4, significantly positive associations were demonstrated with high TSH-low FT4 group, with the strongest association observed for PM₁₀ (adjusted odds ratio [aOR], 1.55; 95% confidence interval [CI], 1.42-1.69), followed by SO₂ (1.38, 1.28-1.49), NO₂ (1.36,1.23-1.50), PM_2.5 (1.25, 1.17-1.34), and CO (1.23, 1.15-1.31). The sex-stratified analyses demonstrated more prominent associations among females.</p><p><strong>Conclusions: </strong>Yearly exposure levels of air pollutants were positively associated with TSH, negatively associated with FT4 levels, and significantly associated with high TSH-low FT4. These findings suggest that exposure to ambient air pollution may contribute to thyroid function alterations at the population level, highlighting the importance of air quality improvement. Further longitudinal studies were warranted to consolidate these findings.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"2679-2691"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic classification and medical decision of idiopathic asthenozoospermia based on metabolomics analysis of seminal plasma.","authors":"Chi Zhang, Xue Zhou, LaiQing Zhu, Liang Shi","doi":"10.1007/s40618-026-02935-y","DOIUrl":"10.1007/s40618-026-02935-y","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic asthenozoospermia(IA) is diagnosed when decreased or absent sperm motility is observed without an identifiable cause through standard clinical evaluations. So far, there have been no reports on the metabolomic classification of IA.</p><p><strong>Methods: </strong>Seminal plasma metabolites were profiled using gas chromatography-mass spectrometry (GC-MS) in 52 healthy controls and 50 patients with IA. Non-negative matrix factorization (NMF) was applied to 62 identified metabolites to classify IA cases into metabolic subtypes, followed by multivariate analyses to characterize the metabolic dysregulation patterns across clusters.</p><p><strong>Results: </strong>NMF identified three distinct IA subtypes with progressively dysregulated metabolic profiles. Eight core metabolites, including citric acid and cholesterol, were consistently altered across all clusters, suggesting shared pathophysiological mechanisms. Cluster 1 showed 10 unique differential metabolites, particularly reduced inositol levels. Cluster 2 was characterized by significantly higher glucose levels compared with other asthenozoospermia cases. Cluster 3 displayed markedly elevated pyruvate levels as a key metabolic feature.</p><p><strong>Conclusion: </strong>This study provides the first NMF-based metabolomic classification of IA, revealing heterogeneous metabolic signatures among patients. These findings may support refined diagnostic classification and more rational clinical drug use for IA.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"2769-2783"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148158379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and genetic insights into Autosomal Dominant Hypocalcemia type 1: a single-center case series including genotype-phenotype correlations, pregnancy outcomes, and novel CASR variants.","authors":"Simone Della Valentina, Laura Pierotti, Chiara Sardella, Anna Dal Lago, Elena Pardi, Angela Michelucci, Maria Adelaide Caligo, Paolo Piaggi, Piercarlo Rossi, Filomena Cetani","doi":"10.1007/s40618-026-02928-x","DOIUrl":"10.1007/s40618-026-02928-x","url":null,"abstract":"<p><strong>Purpose: </strong>The main purpose of this study was to provide a comprehensive characterization of adult patients with Autosomal Dominant Hypocalcemia type 1 (ADH1), focusing on clinical and biochemical features, with particular attention to renal involvement, skeletal features and ectopic calcifications. The secondary aims were to explore potential genotype-phenotype correlations, describe two previously unreported CASR variants, and report pregnancy outcomes in affected women.</p><p><strong>Methods: </strong>We conducted a retrospective, single-centre study of 11 adults with genetically confirmed ADH1 followed at a tertiary Endocrinology Unit between March 2012 and May 2025. Clinical presentation, biochemical data, renal and cerebral involvement, skeletal status and treatment history were collected at first evaluation and during follow-up. CASR variants were identified by next-generation sequencing with Sanger confirmation, and genotype-phenotype relationships were explored.</p><p><strong>Results: </strong>At diagnosis, 64% of patients reported hypocalcemia-related symptoms, while 36% were asymptomatic. Nephrolithiasis, nephrocalcinosis and basal ganglia calcifications were frequent, in patients exposed to long-term calcium and active vitamin D therapy, although causal relationships cannot be established. Axial BMD was normal or increased, whereas radial BMD was often reduced and bone turnover markers were low-normal; no fragility fractures were documented. We identified two novels CASR missense variants and observed marked intra- and interfamilial variability. Four pregnancies in three women with ADH1 resulted in favourable maternal and neonatal outcomes.</p><p><strong>Conclusions: </strong>In our ADH1 patients we found a wide clinical variability, from asymptomatic hypocalcemia to severe early-onset disease, with a high burden of renal complications and ectopic calcifications. Genotype alone does not fully predict clinical severity, even for the same CASR variant. Pregnancies can have good outcomes under close biochemical monitoring and tailored therapy but should be managed as high-risk.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"2865-2881"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148139483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adult mice are more susceptible to high-fat diet-induced visceral adiposity and insulin resistance than juvenile mice.","authors":"Miloš Vratarić, Isidora Alempijević, Biljana Bursać, Ana Teofilović, Danijela Vojnović Milutinović, Ana Djordjevic","doi":"10.1007/s40618-026-02938-9","DOIUrl":"10.1007/s40618-026-02938-9","url":null,"abstract":"<p><strong>Purpose: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"2963-2974"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148354469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}