Journal of the Endocrine Society最新文献

{"title":"Natural history of a pediatric cohort with islet autoantibody positivity: a single-center retrospective cohort study.","authors":"Emilio Casalini, Donella Puliti, Barbara Piccini, Matteo Cerutti, Silvia Farina, Emanuela Laudani, Lorenzo Lenzi, Stefano Romano, Francesco Citera, Maria Moriondo, Salvatore De Masi, Sonia Toni","doi":"10.1210/jendso/bvag087","DOIUrl":"https://doi.org/10.1210/jendso/bvag087","url":null,"abstract":"<p><strong>Context: </strong>Type 1 diabetes (T1D) progresses from genetic risk to metabolic disease. Anti-β-cell antibodies (AABs), alongside clinical features, define the stages of T1D and enable identification of presymptomatic individuals.</p><p><strong>Objective: </strong>To describe the natural history of patients with ≥1 positive AAB, analyzing progression to stage 3 T1D and clinical severity at diagnosis.</p><p><strong>Design: </strong>Single-center retrospective cohort study (February 2012-April 2025).</p><p><strong>Patients: </strong>One-hundred and six patients with ≥1 AAB-positive enrolled in a structured follow-up program.</p><p><strong>Main outcome measure: </strong>progression to stage 3 T1D and occurrence of diabetic ketoacidosis (DKA) at diagnosis.</p><p><strong>Results: </strong>During a median follow-up of 4 years, 19 of 106 AAB-positive patients progressed to stage 3 T1D, none of whom presented with DKA at diagnosis. The 5-year cumulative risk of progression was 16.6% (95% CI: 10.0%-26.9%). Patients with multiple AAB positivity at baseline had a significantly higher 5-year risk than those with a single positive AAB (40.4% vs 8.3%; <i>P</i> = .0002). Glutamic acid decarboxylase (GAD) autoantibody positivity was associated with an increased 5-year risk of progression (25.7% vs 2.8% in GAD-negative children; <i>P</i> = .0063) and remained independently associated with T1D onset in multivariable analysis.</p><p><strong>Conclusion: </strong>Persistent autoantibody positivity, particularly for GAD, is strongly associated with progression to stage 3 T1D. Children identified through AAB monitoring show a milder clinical presentation at diagnosis, with no cases of DKA. These data support screening and structured follow-up of at-risk children, which may help prevent DKA and facilitate identification of candidates for disease-modifying interventions.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 5","pages":"bvag087"},"PeriodicalIF":3.1,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma metabolites after 10-weeks of glucose vs fructose-sweetened beverages in subjects with overweight/obesity.","authors":"Mélanie Guirette, Danielle E Haslam, Jiantao Ma, Peter J Havel, Kimber L Stanhope, Olga Ilkayeva, Christopher B Newgard, Nicola M McKeown, Mark A Herman","doi":"10.1210/jendso/bvag097","DOIUrl":"https://doi.org/10.1210/jendso/bvag097","url":null,"abstract":"<p><p>To identify metabolites as potential biomarkers of fructose vs glucose consumption and related metabolic changes, we conducted exploratory metabolomic profiling of fasting blood samples from participants in a double-blind, parallel-arm trial involving 31 male and female adults with overweight or obesity, both before and after supplementation with glucose- or fructose-sweetened beverages. Orthogonal Partial Least Square Discriminatory Analysis (OPLS-DA) was used to identify metabolites that could discriminate between the 2 intervention groups. Changes in 16 metabolites (5 of which are branched-chain amino acid catabolic pathway metabolites) and the branched chain keto acid (BCKA) composite score showed nominal (FDR adjusted <i>P</i>-value < .2, unadjusted <i>P</i>-value ≤ .08) differences in response to the 2 interventions. We observed a 2.19 µM (or 13%) and a 10.17 µM (or 25%) increase in ketomethylvaleric acid (<i>P</i> _FDR = 0.04, <i>P</i> = .001) and 2-hydroxybutyrate (<i>P</i> _FDR = 0.11, <i>P</i> = .008), respectively, after glucose supplementation compared to a null change after fructose supplementation. Notable trends after fructose supplementation included increased long- and median-chain acylcarnitines (ACs); decreased short-chain ACs; and increased homocysteine compared to the glucose supplementation. These data suggest that in people with overweight/obesity, consumption of beverages high in glucose vs fructose may differentially affect the metabolism of branched-chain amino acids and acylcarnitine species reflective of changes in fatty acid oxidation and de novo lipogenesis.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 5","pages":"bvag097"},"PeriodicalIF":3.1,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Greater reduction in the proinsulin-C-peptide ratio with a ketogenic vs control diet in patients with type 2 diabetes.","authors":"Marian L Yurchishin, Amanda R Finn, Lauren A Fowler, Sara L Vere-Whiting, Barbara A Gower","doi":"10.1210/jendso/bvag073","DOIUrl":"https://doi.org/10.1210/jendso/bvag073","url":null,"abstract":"<p><strong>Context: </strong>The proinsulin to C-peptide (PICP) ratio reflects beta-cell stress and has been shown to decrease following diet-induced weight loss.</p><p><strong>Objective: </strong>To compare the changes in PICP following a ketogenic (KD) or a low-fat diet (LFD) in individuals with type 2 diabetes (T2D).</p><p><strong>Methods: </strong>The sample was 55 (±7) years of age, majority female (76%), and 54% African American. Participants (n = 51) were randomized to either a KD or a LFD for 12 weeks. PICP and the acute (ACP) and maximal (CPmax) C-peptide responses were determined using a hyperglycemic clamp. Multiple linear regression analyses were used to examine the effect of diet on changes in PICP. Spearman correlations were conducted to evaluate associations between changes in fasting and post-clamp PICP with changes in beta-cell function.</p><p><strong>Results: </strong>Diet assignment was a significant predictor of change in fasting PICP (PICP₀) (KD vs LFD β = -0.18 [-11.16, -0.05]) after adjusting for 12-week fasting glucose and baseline PICP₀. Results were similar when 190-minute PICP (PICP₁₉₀) was used as the outcome variable (KD vs LFD β = -0.23 [-6.99, -1.19]), after adjusting for 12-week fasting glucose and baseline PICP₁₉₀. Spearman correlation analyses revealed that the change in ACP was inversely associated with changes in both PICP₀ (ρ = -0.37, <i>P</i> = .009) and PICP₁₉₀ (ρ = -0.38, <i>P</i> = .01) over the 12-week study.</p><p><strong>Conclusion: </strong>A KD decreases the proportion of proinsulin secreted to a greater extent than a LFD in patients with early T2D, a change that was associated with an improvement in beta-cell function.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 5","pages":"bvag073"},"PeriodicalIF":3.1,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13097434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Weight loss lifestyle intervention and bone health hormonal markers in type 2 diabetes: analysis from look AHEAD study.","authors":"Jiahuan Helen He, Chigolum P Oyeka, Jianqiao Ma, Nityasree Srialluri, Teresa Gisinger, Mark Woodward, Erin D Michos, Karen C Johnson, Kendall F Moseley, Wendy L Bennett, Dhananjay Vaidya","doi":"10.1210/jendso/bvag089","DOIUrl":"https://doi.org/10.1210/jendso/bvag089","url":null,"abstract":"<p><strong>Context: </strong>Intensive lifestyle interventions (ILI) in people with type 2 diabetes (T2D) not only promote weight loss but are also associated with bone loss and increased fracture risk. The hormonal mechanisms regulating calcium metabolism that may underlie these changes remain to be investigated.</p><p><strong>Objective: </strong>To evaluate the association between a weight loss-targeted ILI on 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), and vitamin D-binding protein (VDBP) in adults with T2D.</p><p><strong>Methods: </strong>We derived data from a randomly selected subset of participants (n = 123) from Look AHEAD (Action for Health in Diabetes), a randomized controlled trial comparing ILI (caloric restriction and physical activity) with diabetes support and education (DSE) in adults with overweight/obesity and T2D. Covariate-adjusted linear mixed regressions were used to examine the effect of ILI on changes in 25(OH)D, PTH, and VDBP at year 1 (weight-loss nadir) and year 4.</p><p><strong>Results: </strong>At year 1, 25(OH)D had an ILI-related increase of 2.04 ng/mL (95% CI: 0.20, 3.88) and PTH had an ILI-related suppression of -6.75 pg/mL (95% CI: -11.4, 2.13). By year 4, these effects were no longer observed as DSE had a delayed increase in 25(OH)D and PTH returned to baseline levels in both groups. No significant treatment effect was observed for VDBP.</p><p><strong>Conclusion: </strong>Intensive lifestyle intervention was associated with an increase in 25(OH)D and suppression of PTH elevation during the period of maximal weight loss. These findings suggest that weight loss-targeted lifestyle interventions may influence hormones regulating calcium metabolism, highlighting the need to examine whether such hormonal alterations contribute to bone mineralization during weight loss.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 5","pages":"bvag089"},"PeriodicalIF":3.1,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13107178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intrauterine gestational diabetes mellitus, child anxiety, and internalizing symptoms: moderation by physical activity.","authors":"Jasmin M Alves, Megan Herting, Ting Chow, Anny H Xiang, Kathleen A Page","doi":"10.1210/jendso/bvag095","DOIUrl":"https://doi.org/10.1210/jendso/bvag095","url":null,"abstract":"<p><strong>Context: </strong>Prenatal exposure to gestational diabetes mellitus (GDM) is linked to increased risk for offspring mental health disorders, yet few studies account for maternal mental health or potential protective factors.</p><p><strong>Objective: </strong>This work aimed to examine whether prenatal GDM exposure is associated with child anxiety and depressive symptoms, independent of maternal depression, and whether child physical activity (PA) modifies these associations.</p><p><strong>Methods: </strong>In this retrospective cohort study, data included 138 child-mother dyads (mean [SD] child age: 11.1 [2.5] years; 40% GDM-exposed; 56% female) from the BrainChild study. GDM status was extracted from electronic medical records. Children completed the State-Trait Anxiety Inventory for Children, Center for Epidemiological Studies Depression Scale for Children, Child Behavior Checklist, and a 3-day PA recall. Mothers completed the Center for Epidemiological Studies Depression Scale. Linear regression models, adjusted for child age, sex, puberty, and maternal depression, assessed associations between GDM exposure and mental health outcomes and tested moderation by moderate-to-vigorous physical activity (MVPA).</p><p><strong>Results: </strong>GDM-exposed children had higher parent-reported internalizing symptoms compared with unexposed children (β = 3.22; <i>P</i> < .01), independent of maternal depressive symptoms. MVPA significantly interacted with GDM exposure in such a way that the high MVPA group showed no association between GDM exposure and trait anxiety, while the low-MVPA group showed that GDM exposure was associated with higher trait anxiety (β = 4.11; <i>P</i> < .01).</p><p><strong>Conclusion: </strong>Prenatal GDM exposure was associated with greater internalizing symptoms during preadolescence, independent of maternal depression. Engagement in recommended PA levels mitigated the relationship between GDM-exposure and child anxiety, suggesting PA may protect against anxiety-related outcomes. Future prospective studies are needed to confirm these findings.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 5","pages":"bvag095"},"PeriodicalIF":3.1,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skeletal muscle mitochondrial bioenergetics in pregnancy: a comparison of in vivo and in vitro outcomes.","authors":"Ericka M Biagioni, Polina M Krassovskaia, Gillian Tiralla, Kelsey H Fisher-Wellman, Chien-Te Lin, Abby D Altazan, R Caitlin Hebert, Sripallavi Yendamuri, Maninder Singh, Owen T Carmichael, P Darrell Neufer, Kristen E Boyle, Leanne M Redman, Nicholas T Broskey","doi":"10.1210/jendso/bvag093","DOIUrl":"https://doi.org/10.1210/jendso/bvag093","url":null,"abstract":"<p><strong>Purpose: </strong>Exercise-mediated adaptations to mitochondria are well established in nongravid populations; however, the extent to which these adaptations occur during pregnancy remains unclear. Therefore, the objective of this study was to compare skeletal muscle mitochondrial bioenergetics in physically active (<i>n</i> = 10) vs sedentary (<i>n</i> = 9) pregnant women.</p><p><strong>Methods: </strong>Groups were matched for age, race, and pregravid body mass index and were studied in the second (T2; weeks 21-25) and third trimester (T3; weeks 31-35). Free-living physical activity was assessed by accelerometry and aerobic fitness by peak oxygen uptake (VO₂peak) testing. In vivo mitochondrial capacity was assessed by ³¹P-magnetic resonance spectroscopy. Primary skeletal muscle myotubes were obtained via muscle biopsy between late T2 and early T3. Mitochondrial in vitro respiration was assessed by high-resolution respirometry, and mitochondrial content was measured by Western blot and enzyme activity.</p><p><strong>Results: </strong>Despite a decline in physical activity across gestation, active women maintained a higher VO₂peak at T2 (<i>P</i> < .05) and T3 (<i>P</i> < .01) compared with sedentary. There were no differences in phosphocreatine recovery time between groups or timepoints. Myotube mitochondrial respiratory capacity was similar between groups; however, compared with sedentary mothers, active mothers demonstrated increased expression of mitochondrial complexes I, II, and IV proteins (all <i>P</i> < .05). Additionally, myotube mitochondrial efficiency (adenosine triphosphate-to-oxygen consumption ratio) measures were positively correlated with maternal VO₂peak at T3 (r = 0.49, <i>P</i> < .05), suggesting a link between fitness and mitochondrial efficiency.</p><p><strong>Conclusion: </strong>These findings suggest that late pregnancy may blunt mitochondrial adaptations to aerobic exercise despite a preservation of cardiovascular fitness. Future studies are needed to determine whether increasing activity throughout gestation can enhance mitochondrial respiration.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 5","pages":"bvag093"},"PeriodicalIF":3.1,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between thyroidea function and opioid agonist therapy: a prospective cohort study from Norway.","authors":"Anne Taraldsen Heldal, Jorn Henrik Vold, Kristin Viste, Fatemeh Chalabianloo, Gunnar Mellgren, Kjell Arne Johansson, Lars Thore Fadnes","doi":"10.1210/jendso/bvag079","DOIUrl":"https://doi.org/10.1210/jendso/bvag079","url":null,"abstract":"<p><strong>Background: </strong>Opioid agonist therapy (OAT) is an essential treatment for opioid dependency. However, OAT may lead to endocrinopathy, which may impair the tolerability of treatment. Although the risk of disturbed regulation of the adrenal and gonadal axes has been extensively studied, less is known about how long-term opioid use and corresponding risk factors influence the thyroid axis. The objective of this study was to investigate associations between biomarkers of thyroid function and OAT medication as well as sociodemographic and clinical factors and concurrent use of illicit substances among patients receiving OAT.</p><p><strong>Methods: </strong>We used prospective data from 320 people receiving OAT in Bergen, Norway, from 2016 through 2023. All had 2 health assessments, including serum measurements of TSH. Descriptive statistics and a linear mixed model with coefficient and 95% CIs were performed to investigate the association between serum TSH (measured in mIU/L) and OAT medication as well as age, sex, substance use patterns, injecting use, housing status, and educational attainment at first assessment and over time.</p><p><strong>Results: </strong>Median serum TSH at first assessment in the study population was 1.8 mIU/L (interquartile range: 1.2). No association between OAT medications, sociodemographic, or clinical factors and serum TSH was found at first assessment and over time.</p><p><strong>Conclusion: </strong>The median serum TSH was within the recommended range among people receiving OAT. No association between OAT treatment and thyroid insufficiency was found. This indicates that screening for thyroid function beyond symptomatic assessment is probably not needed among patients receiving OAT.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 5","pages":"bvag079"},"PeriodicalIF":3.1,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determinants of diagnostic delay in thyroid storm: a 12-year single-center cohort study.","authors":"Tetsuya Kawahara, Mikio Toda, Maiko Kanagawa, Nagahiro Toyama, Chie Kawahara, Tetsuya Inazu","doi":"10.1210/jendso/bvag088","DOIUrl":"https://doi.org/10.1210/jendso/bvag088","url":null,"abstract":"<p><strong>Objective: </strong>Thyroid storm is a life-threatening endocrine emergency. Although predictors of mortality have been described, determinants of diagnostic delay remain unclear. We aimed to identify factors associated with diagnostic delay in thyroid storm and its relationship with severe clinical outcomes.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study of adults admitted with thyroid storm at a tertiary-care hospital over 12 years. The primary endpoint was time from symptom onset to diagnosis (days). Factors associated with time to diagnosis were evaluated using multivariable linear regression adjusting for predefined covariates, including age, initial onset vs recurrence, admitting department, presenting symptoms, and cardiac rhythm abnormalities. Secondary analyses examined delayed diagnosis (≥7 days) using multivariable logistic regression. Additional analyses separated diagnostic delay into patient-related and in-hospital components and evaluated admission pathways and referral status.</p><p><strong>Results: </strong>Ninety-one patients were included. Median time to diagnosis was 5 days (interquartile range 3.5-7). Older age (1.08 days per 10-year increase; <i>P</i> < .001), initial onset (4.10 days; <i>P</i> < .001), and admission to non-emergency departments (2.76 days; <i>P</i> = .004) were independently associated with longer diagnostic delay, whereas symptom patterns and thyroid hormone levels were not. Patient-related delay did not differ by admission pathway, but in-hospital delay was longer among non-emergency admissions. Delayed diagnosis was associated with increased need for intensive care and organ support.</p><p><strong>Conclusion: </strong>Diagnostic delay in thyroid storm appears driven mainly by clinical pathways rather than symptom patterns or biochemical severity. Earlier consideration of thyroid storm and prompt thyroid testing-particularly at initial onset and in non-emergency settings-may improve outcomes.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 5","pages":"bvag088"},"PeriodicalIF":3.1,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Placental gene signatures associated with high neonatal adiposity: role for immune cell activation.","authors":"Jason Laird, Deepak Venkataraman, Hannah Yen, Chelsea Liu, Patrick Catalano, Ruggero Spadafora, Nanguneri Nirmala, Perrie O'Tierney-Ginn","doi":"10.1210/jendso/bvag071","DOIUrl":"https://doi.org/10.1210/jendso/bvag071","url":null,"abstract":"<p><p>Fetal fat accumulation is an important indicator of the nutritional environment in pregnancy and placental function. Excessive fat accretion leading to high adiposity at birth, however, can increase a child's long-term risk for obesity and metabolic disease. While maternal body mass index is associated with neonatal adiposity, there is a wide variation in body composition among babies born to women with and without obesity. The placenta orchestrates a complex exchange of nutrients and signals between the mother and baby. To better understand the molecular mechanisms that govern fetal fat accumulation, we profiled the transcriptomics of 79 placentas collected from mothers with and without obesity. We identified a set of 18 neonatal adiposity-associated genes, common to pregnancies with and without obesity. A coexpressed cluster of these genes is involved in innate immune responses, particularly neutrophil activation. We also identified neonatal adiposity-associated genes unique to mothers with or without obesity, suggesting different biological pathways support high newborn adiposity, and/or are responsive to a common initial immune signal. These findings suggest that placental inflammation may influence fetal fat accumulation. Understanding these pathways may help identify novel ways to support healthy fetal growth and reduce the risk of long-term disease.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 4","pages":"bvag071"},"PeriodicalIF":3.1,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13061145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147645768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Burosumab treatment in an adult with FGF23-mediated hypophosphatemia due to cutaneous skeletal hypophosphatemia syndrome.","authors":"Laura L Tosi, Elmer N Rajah, Austin P Gillies, Mirini Kim, Kendall Reid, Rachel I Gafni","doi":"10.1210/jendso/bvag040","DOIUrl":"10.1210/jendso/bvag040","url":null,"abstract":"<p><strong>Context: </strong>Cutaneous skeletal hypophosphatemia syndrome (CSHS) is an ultrarare disorder defined by epidermal and/or melanocytic nevi, mosaic skeletal dysplasia, and FGF23-mediated hypophosphatemia. As in other FGF23-mediated hypophosphatemia conditions, individuals with CSHS have renal phosphate wasting and inappropriately normal or frankly low 1,25-dihydroxyvitamin D levels with resultant hypophosphatemia leading to rickets and osteomalacia. Conventional therapy for FGF23-mediated hypophosphatemia consists of multiple daily doses of oral phosphate and active vitamin D.</p><p><strong>Objective: </strong>Burosumab is a fully human immunoglobulin G1 monoclonal antibody that binds to and inhibits the activity of FGF23, leading to an increase in serum phosphorus levels and skeletal healing. Given its efficacy in tumor-induced osteomalacia and X-linked hypophosphatemic rickets, two related disorders of FGF23-mediated hypophosphatemia, we explored treatment with burosumab in a young adult with CSHS.</p><p><strong>Methods: </strong>In this open-label, single-patient trial conducted in the clinical research unit of an academic children's hospital, burosumab was administered subcutaneously every 4 weeks for 3 years. The participant was an 18-year-old woman with CSHS and FGF23-mediated hypophosphatemia. Burosumab was administered subcutaneously every 4 weeks, starting at 0.3 mg/kg/dose and increasing up to 0.9 mg/kg/dose. Main outcome measures included change in blood phosphorus levels.</p><p><strong>Results: </strong>Burosumab therapy was well tolerated with correction of hypophosphatemia and improvement in other measures including renal phosphate loss, alkaline phosphatase, active vitamin D metabolism, skeletal imaging, pain, physical function, and overall quality of life. Adverse events were manageable, with unclear relationship to burosumab treatment.</p><p><strong>Conclusion: </strong>These findings suggest that burosumab may be an effective treatment for CSHS.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 4","pages":"bvag040"},"PeriodicalIF":3.1,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13022826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147574845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}