Journal of the Endocrine Society最新文献

{"title":"Unraveling the natural history of lipodystrophy syndromes: insights from the prospective LD-Lync study.","authors":"Merve Celik Guler, Maria Cristina Foss-Freitas, Ilgin Yildirim Simsir, Matheos Yosef, Michelle Ashmus, Shokoufeh Khalatbari, Donatella Gilio, Demircan Guler, Diarratou Kaba, Anabela Dill Gomes, Trinity Neal, Becca Tuska, Maiah Brush, Andra Stratton, Rasimcan Meral, Ozge Besci, Michael Hwang, Britney Tracey, Drake Stanton Rosenberg, Chika Divine Uwandu, Marinna Okawa, Brianna Brite, Marissa Lightbourne, Yingying Luo, Deanna Jones, Kaneesha Wallace, Cathie Spino, Natalia Prado Boris, Abdelwahab Jalal Eldin, Cynthia M Valerio, Virginia Oliveira Fernandes, Renan Magalhães Montenegro Junior, Baris Akinci, Rebecca J Brown, Elif A Oral","doi":"10.1210/jendso/bvag155","DOIUrl":"10.1210/jendso/bvag155","url":null,"abstract":"<p><strong>Context: </strong>Lipodystrophy syndromes represent a diverse group of rare disorders characterized by deficiency and abnormal distribution of adipose tissue that may be generalized (GL) or partial (PL), leading to significant metabolic abnormalities.</p><p><strong>Objective: </strong>To elucidate the natural history of critical comorbidities of lipodystrophy.</p><p><strong>Methods: </strong>Ongoing, prospective, multicenter, registry study (LD Lync; NCT03087253). This analysis reports 266 patients with lipodystrophy enrolled until October 11, 2023.</p><p><strong>Results: </strong>The median age was 39 years ([28-54], range: 6-76 years; male/female: 50/216). Hypertriglyceridemia (<i>n</i> = 202, 75.9%) was the most common comorbidity, followed by diabetes (<i>n</i> = 190, 72.0%), hepatic steatosis (<i>n</i> = 182, 68.4%), and hypertension (<i>n</i> = 130, 48.8%). Pancreatitis was detected in 21.8% of patients (<i>n</i> = 58), and cirrhosis in 7.1% of patients (<i>n</i> = 19). The median age at diagnosis was significantly earlier in patients with GL compared to those with PL for both diabetes (16 [14-32] years in GL vs 35 [25-50] years in PL) and hypertriglyceridemia (20 [15-26] years in GL vs 30 [22-49] years in PL) (<i>P</i> < .0001). Seven (2.6%) patients died during follow-up. Multiple medications were used to treat metabolic disease. Eighty-one (30.4%) patients received at least one dose of metreleptin during clinical studies or commercially during follow-up.</p><p><strong>Conclusion: </strong>Our findings confirm that patients with lipodystrophy face a significant risk of comorbidities, with an earlier onset of diabetes, hypertriglyceridemia, and hepatic steatosis in those with GL compared to PL. This registry will serve as a crucial resource for gaining insights into the burden of disease in lipodystrophy.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 8","pages":"bvag155"},"PeriodicalIF":4.4,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13409154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620666","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":"Rare germline variants in canonical and candidate genes in apparently sporadic bilateral primary aldosteronism.","authors":"Lucas S Santana, Débora K Alves-Fernandes, Jose Antonio B Lima Sobrinho, Felipe Freitas-Castro, Lucas B Rossetti, Jessica Okubo, Gustavo F C Fagundes, Eduardo Z Kawahara, Thiago S Mendes, Luiz A Bortolotto, Andrea Pio-Abreu, Giovanio V Silva, Luciano F Drager, Ana Claudia Latronico, Madson Q Almeida","doi":"10.1210/jendso/bvag167","DOIUrl":"10.1210/jendso/bvag167","url":null,"abstract":"<p><strong>Background: </strong>The germline genetic basis of bilateral primary aldosteronism (PA) remains poorly understood, particularly in apparently sporadic disease. We investigated rare germline variants in canonical and candidate genes in patients with bilateral PA associated with resistant hypertension and/or hypertension diagnosed before 40 years of age.</p><p><strong>Methods: </strong>We studied 53 individuals with bilateral PA after exclusion of familial PA types 1 and 3. Whole-exome sequencing was performed in 52 probands and 1 affected relative. Variant prioritization was restricted to genes with direct or indirect evidence linking them to PA using a virtual panel approach. Clinical, biochemical, and imaging data were compared between carriers and noncarriers.</p><p><strong>Results: </strong>Nine of 53 patients (17%) harbored at least one rare germline candidate variant. Variants in canonical PA genes were identified in 5 patients (9.6%), including <i>CACNA1H</i> (<i>n</i> = 4) and <i>CACNA1D</i> (<i>n</i> = 1). In 4 patients (7.5%), rare variants were identified in plausible candidate genes (<i>ANO1, KCNK3, CASZ1,</i> and <i>STRN</i>). All prioritized variants were classified as variants of uncertain significance. Compared with noncarriers, carriers showed a lower frequency of hypokalemia (<i>P</i> < .0001), higher prevalence of family history of hypertension (<i>P</i> < .0001), higher frequency of resistant hypertension (<i>P</i> < .0001), required more antihypertensives (<i>P</i> = .0264), and had more frequent adrenal computed tomography abnormalities, particularly bilateral involvement (<i>P</i> < .0001).</p><p><strong>Conclusion: </strong>Rare germline variants in canonical and candidate genes were identified in a subset of patients with apparently sporadic bilateral PA. Variants in established genes, particularly <i>CACNA1H</i>, were relatively frequent, with additional variants in biologically plausible candidates.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 9","pages":"bvag167"},"PeriodicalIF":4.4,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13453528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148707002","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":"Real-world outcomes in patients with tumor-induced osteomalacia treated vs not treated with burosumab.","authors":"María Belén Zanchetta, Kathryn M Dahir, Erik A Imel, Thomas O Carpenter, Kerry Sandilands, Ben Johnson, Zhiyi Li, Lucinda Camidge, Elke Rottier, Emma Wilkes, Emily Vinall, Soraya Sader, Suzanne M Jan de Beur","doi":"10.1210/jendso/bvag165","DOIUrl":"10.1210/jendso/bvag165","url":null,"abstract":"<p><strong>Context: </strong>Tumor-induced osteomalacia (TIO) is an ultra-rare condition caused by tumors secreting fibroblast growth factor-23, leading to chronic hypophosphatemia, pain, muscle weakness, fractures, and impaired physical function. Burosumab is a monoclonal antibody indicated for treatment of TIO when tumors cannot be curatively resected.</p><p><strong>Objective: </strong>This study compares clinical and patient-reported outcomes in patients with TIO treated vs not treated with burosumab in a real-world setting.</p><p><strong>Design: </strong>This interim analysis reports outcomes at enrollment in the prospective, observational Tumor-Induced Osteomalacia Disease Monitoring Program (NCT04783428), stratified by burosumab treatment status at enrollment.</p><p><strong>Setting: </strong>Tertiary care centers in the United States and Argentina.</p><p><strong>Patients: </strong>Patients with TIO from the Disease Monitoring Program.</p><p><strong>Exposure: </strong>Burosumab treatment.</p><p><strong>Main outcome measures: </strong>Biochemistry measurements and patient-reported health-related quality of life (pain, fatigue, and physical function).</p><p><strong>Results: </strong>21 patients with TIO (61.9% female, median [Q1, Q3] age 49.7 years [41.6, 57.3]) were included. At enrollment, 11 (52.4%) patients were treated with burosumab, for a median (Q1, Q3) duration of 4.1 years (0.8, 7.0). Burosumab-treated patients had significantly higher serum phosphate and 1,25-dihydroxyvitamin D levels, and nonsignificantly lower alkaline phosphatase levels, compared with patients not treated with burosumab. Patients treated with burosumab reported significantly lower median Brief Pain Inventory scores, nonsignificantly lower Brief Fatigue Inventory scores, and nonsignificantly higher Patient-Reported Outcomes Measurement Information System Physical Function and Short-Form-36 scores, indicating lower symptom severity and better health-related quality of life.</p><p><strong>Conclusion: </strong>This study suggests favorable biochemical and patient-reported outcomes in patients with TIO treated with burosumab.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 9","pages":"bvag165"},"PeriodicalIF":4.4,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13453538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148707059","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":"Genotype-refined 17OHP cut-offs diagnosing nonclassical CAH due to 21OH deficiency in children with premature pubarche.","authors":"Nathalia Bordeira Chagas, Ayrton C Moreira, Margaret de Castro, Sonir R Antonini","doi":"10.1210/jendso/bvag162","DOIUrl":"10.1210/jendso/bvag162","url":null,"abstract":"<p><strong>Context: </strong>Premature pubarche (PP) is a frequent reason for endocrine evaluation. Between 5% and 20% of children presenting with PP may have 21OHD nonclassic congenital adrenal hyperplasia (21OHD-NCAH).</p><p><strong>Objective: </strong>To define optimal basal and ACTH-stimulated 17OHP cutoffs for diagnosing 21OHD-NCAH in children with PP, using <i>CYP21A2</i> genotyping as the gold standard.</p><p><strong>Design setting and patients: </strong>A diagnostic accuracy study including 203 children with PP (median age: 7.5 years [6.4-8.3]; 85% female) who underwent ACTH stimulation testing. Biallelic pathogenic variants upon <i>CYP21A2</i> genotyping defined 21OHD-NCAH.</p><p><strong>Main outcome measures: </strong>Diagnostic performance of basal and post-ACTH 17OHP levels assessed by ROC curve analysis and thresholds defined according to the Youden index.</p><p><strong>Results: </strong>21OHD-NCAH was confirmed in 32 children (15.7%; 7.1 years [6.1-8.6]; 78% female). Basal 17OHP demonstrated excellent diagnostic accuracy (AUC = 0.98). A cutoff of 170 ng/dL (5.1 nmol/L) provided the best diagnostic balance, with 97% sensitivity and 91% specificity. A higher threshold of 410 ng/dL (12.4 nmol/L) achieved 100% specificity but reduced sensitivity (75%), whereas a lower cutoff of 118 ng/dL (3.5 nmol/L) yielded 100% sensitivity at the expense of specificity (84%). A post-ACTH 17OHP > 1104 ng/dL (33.4 nmol/L) yielded 100% sensitivity and specificity. Androgen levels overlapped substantially, and no clinical feature reliably distinguished 21OHD-NCAH from PP.</p><p><strong>Conclusion: </strong>Basal 17OHP provides excellent diagnostic accuracy for 21OHD-CAH in children with PP. A dual-threshold strategy is supported: 170 ng/dL (5.1 nmol/L) as optimal screening cutoff and 410 ng/d (12.4 nmol/L) as highly specific diagnostic threshold, obviating ACTH testing. These genotype-anchored, RIA-derived cutoffs are readily applicable in clinical settings using comparable assays.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 8","pages":"bvag162"},"PeriodicalIF":4.4,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13425647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148654117","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":"Frequent antecedent nodules and diagnostic gaps in adrenocortical carcinoma.","authors":"Dipika R Mohan, Cody Weimholt, L Michael Brunt, Taylor C Brown, Sina Jasim","doi":"10.1210/jendso/bvag161","DOIUrl":"10.1210/jendso/bvag161","url":null,"abstract":"<p><strong>Context: </strong>Adrenocortical carcinoma (ACC) is a rare and often fatal malignancy currently only cured by surgery. Large-scale studies have failed to capture benign to malignant transition events, and patients often present with metastatic disease. These observations suggest ACC develops rapidly without a measurable precursor lesion, forming the basis of widely implemented adrenal incidentaloma guidelines.</p><p><strong>Objective: </strong>We aimed to characterize the prevalence of antecedent adrenal nodules, quality of preoperative diagnostic workup, and the impact on survival for adults with ACC.</p><p><strong>Methods: </strong>We analyzed clinical data from 108 consecutive patients referred to a single tertiary academic medical center from 2000 to 2025.</p><p><strong>Results: </strong>Median follow-up was 86.7 months. Strikingly, 31.7% harbored antecedent nodules, indolent for a median 4.68 years before ACC presentation, and ultimately associated with a higher risk of death (adjusted hazard ratio [HR], 2.9; 95% CI, 1.39-6.0). Regarding preoperative evaluation, 46.4% were referred to endocrinology, associated with more complete hormonal assessment; 31.4% had adrenal biopsy, accompanied by increased risk of progression (adjusted HR, 2.53; 95% CI, 1.24-5.2) and death (adjusted HR, 2.22; 95% CI, 1.07-4.6). Patients with high-grade disease received more interventions; those who received mitotane and/or locoregional therapies had improved survival (adjusted HR, 0.31; 95% CI, 0.14-0.71, and adjusted HR, 0.47; 95% CI, 0.23-0.98, respectively).</p><p><strong>Conclusion: </strong>The unexpectedly high prevalence of indolent antecedent adrenal nodules suggests a prolonged, clinically premalignant phase in a subset of ACC. Initial diagnostic evaluation was often incomplete or inappropriately invasive, compromising the preoperative window and patient survival. These findings challenge current surveillance paradigms, revealing an extended but vulnerable window for surgical cure.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 9","pages":"bvag161"},"PeriodicalIF":4.4,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13458147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713055","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":"Influence of body mass index on disease severity and treatment outcomes in primary aldosteronism.","authors":"Marta Araujo-Castro, Jessica Goi, Jacopo Burrello, Silvia Monticone, Paolo Mulatero, Elena Bersano, Holger Schneider, Erik Johann Petersenn, Stephanie Zopp, Virginia Capuzzo, Ana María García Cano, Elena Mena Ribas, Alicia Sanmartín Sánchez, Patricia Martín Rojas-Marcos, Miguel Paja Fano, Patricia Díaz Guardiola, Ángel Rebollo Román, Alicia Rizo Gellida, Marga González-Boillos, Jorge Gabriel Ruiz-Sanchez, Emilia Gómez-Hoyos, Mònica Recasens, Rebeca Barahona San Millan, María José Picón César, Carolina M Perdomo, Cristina Robles Lázaro, José María Recio, María Calatayud, Cesar Gonzalvo Diaz, Cristina Lamas, Joaquín Serrano, Theodora Michalopoulou, Susana Tenes Rodrigo, Fernando Jaén Aguila, Nuria Muñoz Rivas, Eva María Moya Mateo, Rogelio García Centero, Ana Torres, Sonsoles Gutiérrez-Medina, Aster Adel Gamil, Martin Reincke, Paola Parra Ramírez","doi":"10.1210/jendso/bvag142","DOIUrl":"10.1210/jendso/bvag142","url":null,"abstract":"<p><strong>Purpose: </strong>To assess the impact of body mass index (BMI) on disease severity, cardiac remodeling, and clinical and biochemical outcomes after surgical and medical treatment in patients with primary aldosteronism (PA).</p><p><strong>Methods: </strong>This international retrospective study included patients diagnosed with PA in Germany, Italy, and Spain. Patients with available BMI, serum potassium, blood pressure, and basal plasma aldosterone concentration at diagnosis were included. PA severity was classified using the Primary Aldosteronism Severity Classification.</p><p><strong>Results: </strong>A total of 1752 patients were analyzed at baseline; 604 (34.5%) had obesity (BMI ≥30 kg/m²). Patients with obesity were older, more frequently male, and had a higher prevalence of cardiometabolic comorbidities, including type 2 diabetes, cardiovascular disease, left ventricular hypertrophy, and obstructive sleep apnea. PA severity according to the Primary Aldosteronism Severity Classification did not differ significantly between patients with and without obesity; however, the prevalence of severe PA increased progressively across BMI categories (MH test for linear trend: χ²(1) = 3.70, <i>P</i> = .054). Following adrenalectomy, the probability of complete hypertension resolution decreased with increasing BMI, whereas biochemical cure rates were similar. Among patients treated with mineralocorticoid receptor antagonists, obesity was associated with a lower likelihood of complete clinical response, without significant differences in biochemical response.</p><p><strong>Conclusion: </strong>In patients with PA, obesity is associated with a higher burden of cardiometabolic comorbidities and increased prevalence of left ventricular hypertrophy at baseline, as well as with less favorable clinical outcome after both surgical and medical treatment.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 8","pages":"bvag142"},"PeriodicalIF":4.4,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13373475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471518","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":"Low testosterone is a phenotype of visceral adiposity.","authors":"Karl E Friedl, Adam W Potter","doi":"10.1210/jendso/bvag160","DOIUrl":"10.1210/jendso/bvag160","url":null,"abstract":"<p><strong>Context: </strong>Low testosterone in men is associated with obesity. However, body mass index (BMI) and waist circumference (WC), the most common measures of obesity, do not account for fat distribution. Visceral adipose tissue (VAT) may be the more precise metabolic determinant of androgen suppression.</p><p><strong>Objective: </strong>To determine if visceral adiposity better explains variations in testosterone levels than BMI or WC.</p><p><strong>Design and participants: </strong>This was a cross-sectional analysis of 4948 US men, aged 20-59, from the 2011-2016 National Health and Nutrition Examination Survey (NHANES). All participants had morning total testosterone measurements and 4492 had valid VAT measures from dual-energy X-ray absorptiometry. VAT discordance phenotypes were defined as the lowest vs highest quartile of VAT within BMI and (WC) categories.</p><p><strong>Main outcome measures: </strong>Serum total testosterone and sex hormone-binding globulin.</p><p><strong>Results: </strong>Visceral adiposity was strongly and inversely associated with total testosterone. Although VAT, BMI, and WC showed similar overall explanatory value, visceral adiposity identified substantial differences in testosterone among men with similar BMI or WC. Within each BMI category (normal-weight, overweight, and obese), men with high VAT had 33-36% lower testosterone than men with low VAT. Within WC strata, corresponding reductions were 25-39%. Normal-weight men with high VAT had testosterone levels comparable to obese men with low VAT.</p><p><strong>Conclusion: </strong>Visceral adiposity, rather than BMI- or WC-defined obesity, is the primary adiposity correlate of low testosterone in US men. Testosterone deficiency in some men appears to be a phenotype of visceral fat biology rather than obesity per se.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 8","pages":"bvag160"},"PeriodicalIF":4.4,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549618","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":"Fluid regimens for diabetic ketoacidosis in children and adolescents: systematic review and meta-analysis.","authors":"Ridwa Alam, Fozia Memon, Aparna Haryani, Aqsa Ishaq, Hiba Idrees, Fatima Amjad, Eddy Lang, Sajid Bashir Soofi, Shabina Ariff","doi":"10.1210/jendso/bvag148","DOIUrl":"10.1210/jendso/bvag148","url":null,"abstract":"<p><strong>Background: </strong>Diabetic ketoacidosis (DKA), a life-threatening complication of type 1 diabetes, requires prompt fluid resuscitation to restore circulatory volume and correct metabolic abnormalities. However, the optimal fluid type, volume, and tonicity remain unclear due to concerns regarding cerebral injury and electrolyte imbalances.</p><p><strong>Methods: </strong>We searched PubMed, CINAHL, Cochrane, Scopus, Clinicaltrials.gov, and WHO International Clinical Trials Registry Platform without date restrictions for randomized controlled trials (RCTs) evaluating fluid regimens in children with DKA. Risk of bias was assessed using the Cochrane RoB-2 tool, and certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. Meta-analysis was conducted using RevMan 5.4.</p><p><strong>Results: </strong>The review included 10 RCTs (n = 2291). Children receiving a 20 mL/kg bolus followed by 0.9% saline exclusively for rehydration may have a higher risk of adverse events (AEs) than those receiving 10 mL/kg (risk ratio [RR] = 1.11, 95% CI = 1.01-1.23, low certainty of evidence). However, in children given 0.9% saline exclusively for rehydration, there was a significantly lower risk of hypoglycemia in the 20 mL/kg bolus group compared to the 10 mL/kg group (RR = 0.78, 95% CI = 0.62-0.99, high certainty). For rehydration fluid, compared to 0.45% saline, 0.9% saline (48-72 hours) was associated with a higher risk of hypoglycemia (RR = 1.35, 95% CI = 1.06-1.72, high certainty) and AEs (RR = 1.18, 95% CI = 1.05-1.31, low certainty). Over 36 hours, 0.9% saline may be associated with more AEs (RR = 1.15, 95% CI = 1.03-1.27, low certainty).</p><p><strong>Conclusion: </strong>Smaller bolus volumes may be safer than larger ones, and prolonged use of 0.9% saline may increase the risk of hypoglycemia and AEs, although the certainty of evidence was low.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 8","pages":"bvag148"},"PeriodicalIF":4.4,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13370832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148456188","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":"Associations of urinary phthalate metabolite and replacement chemical concentrations with gestational blood pressure.","authors":"Kimberly L Parra, Emma V Preston, Marlee R Quinn, Paige L Williams, Michele R Hacker, Thomas F McElrath, David E Cantonwine, Antonia M Calafat, Julianne Cook Botelho, Blair J Wylie, Camille E Powe, Ellen W Seely, Tamarra James-Todd","doi":"10.1210/jendso/bvag158","DOIUrl":"10.1210/jendso/bvag158","url":null,"abstract":"<p><strong>Introduction: </strong>Some phthalates and their replacements are endocrine disrupting chemicals (EDCs) found in consumer products and linked to hypertensive disorders of pregnancy (HDP). Few studies have evaluated associations between EDCs and gestational blood pressure.</p><p><strong>Objective: </strong>To evaluate associations between EDC biomarkers with gestational blood pressure.</p><p><strong>Methods: </strong>The Environmental Reproductive and Glucose Outcomes study (<i>N</i> = 338) measured urinary concentrations of 18 phthalate and replacement metabolites and systolic (SBP) and diastolic (DBP) blood pressure at 3 pregnancy study visits (median: 12, 19, and 26 weeks' gestation). Individual metabolite concentrations and summary measures based on common source or mechanism (eg, ΣPersonal care products [ΣPCP]) were log₂-transformed, specific-gravity corrected, and modeled continuously and in quartiles. We estimated covariate-adjusted associations of individual metabolites and, summary measures with blood pressure using linear regression, and with HDP using log-binomial regression, assessing metabolite mixtures using Bayesian Kernel Machine Regression.</p><p><strong>Results: </strong>HDP prevalence was 12.7%. Higher concentrations of monoethyl phthalate (MEP) and ΣPCP were most consistently associated with SBP and DBP elevations at visit 3. Higher concentrations of MEP (Q4 vs Q1) were associated with 4.59 mmHg higher SBP (95% CI: 0.04, 9.15), and higher ΣPCP (Q3 vs Q1) were associated with 5.78 mmHg (95% CI: 1.59, 9.97). Higher MEP and ΣPCP (Q4 vs Q1) were positively linked to DBP elevations of 4.51 to 4.70 mmHg. Other phthalate biomarkers were associated with blood pressure at specific time points.</p><p><strong>Discussion: </strong>Certain urinary phthalate biomarkers, particularly MEP and ΣPCP, were associated with higher blood pressure levels in pregnancy, with implications for HDP.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 9","pages":"bvag158"},"PeriodicalIF":4.4,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13456086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148706992","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":"Anthropometry-adjusted TyG indices predict diabetes, graft failure, and mortality in kidney transplant recipients.","authors":"Jiachuan Xiong, Tamas Szili-Torok, Ömer Tarik Özyilmaz, Weiwei Xu, Juul S Daamen, Jip Jonker, Dion Groothof, Daan Kremer, Antonio Gomes Neto, Robert A Pol, Martin H de Borst, Stephan J L Bakker","doi":"10.1210/jendso/bvag157","DOIUrl":"10.1210/jendso/bvag157","url":null,"abstract":"<p><strong>Context: </strong>The triglyceride-glucose (TyG) index is a widely used surrogate marker of insulin resistance and associated with cardiometabolic outcomes. However, the comparative prognostic value of TyG-derived indices, particularly those incorporating anthropometric measures or long-term variability, for adverse outcomes after kidney transplantation remains unclear.</p><p><strong>Objective: </strong>To compare the prognostic performance of 15 TyG-derived indices for predicting new-onset diabetes after transplantation (NODAT), graft failure, and all-cause mortality in kidney transplant recipients (KTRs).</p><p><strong>Design: </strong>This prospective observational study was conducted within the TransplantLines Biobank and Cohort study and included 464 KTRs (median age, 56.9 years; 65.1% male) followed for a median of 71 months. Fifteen TyG-derived indices were classified into metabolic, anthropometry-adjusted, and variability-based domains. Their prognostic performance was assessed using an analytical framework integrating machine learning with conventional statistical methods.</p><p><strong>Results: </strong>Comparative analyses identified 4 indices, TyG-WWI, TyG-WHR, TyG mean, and TyG-BMI, as having superior predictive performance. Among them, anthropometry-adjusted indices (TyG-WHR and TyG-WWI) showed the most stable associations across 3 outcomes. In multivariable analyses, TyG-WHR independently predicted NODAT (HR 2.30, 95% CI 1.21-4.39), graft failure (HR 2.22, 95% CI 1.18-4.18), and mortality (HR 1.87, 95% CI 1.19-2.96), while TyG-WWI independently predicted mortality (HR 2.07, 95% CI 1.11-3.86). Cross-validation showed no consistent advantage of combined models over single well-performing indices.</p><p><strong>Conclusion: </strong>Among adult KTRs from the TransplantLines cohort with a functioning graft, TyG-WWI and TyG-WHR showed the most consistent associations with adverse post-transplant outcomes. Their potential role as complementary metabolic risk markers requires validation in larger and more diverse transplant cohorts.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 8","pages":"bvag157"},"PeriodicalIF":4.4,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549627","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}