Journal of the Endocrine Society最新文献

{"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":"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":4.4,"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":"Clinical characteristics, disease course, and clinical subgroups of young adults with type 2 diabetes.","authors":"Anu Sharma, Jose M Lazaro-Guevara, Devorah Stucki, Sanjiv Anand, Corrine K Welt, Marcus G Pezzolesi","doi":"10.1210/jendso/bvag100","DOIUrl":"10.1210/jendso/bvag100","url":null,"abstract":"<p><strong>Context: </strong>Type 2 diabetes (T2D) in young adults is an emerging entity distinct from that in older adults.</p><p><strong>Objective: </strong>To identify unique clinical subgroups among young adults using clinical variables.</p><p><strong>Methods: </strong>Utilizing the Utah Diabetes Database, a retrospective cohort study was performed with data from 56 327 individuals with T2D as defined by International Classification of Diseases codes and analyzed by predefined groups: young adults (18-44 years) and older adults (≥45 years). De novo k-means clustering was performed.</p><p><strong>Results: </strong>Young adults with T2D (yT2D) were more likely to be female (51%), self-identify as racial/ethnic minorities (24%), and have obesity (68%). Compared to older adults, yT2D at baseline had worse glycemic control (hemoglobin A1c [HbA1c] 7.8 ± 2.5% vs 7.3 ± 2.0%, <i>P</i> < .001), higher body mass index (BMI; 34 ± 9 vs 32 ± 7 kg/m², <i>P</i> < .001) and higher estimated glomerular filtration rate (eGFR; 100 ± 25 vs 73 ± 23 mL/min/1.73 m², <i>P</i> < .001). Over time, the increase in HbA1c and BMI was greater in yT2D compared with older adults (<i>P</i> < .01) with no difference in eGFR change. Three unique clusters were determined: cluster 1 had higher BMI and lower HbA1c; cluster 2 had a higher HbA1c and was more likely to need insulin; and cluster 3 had a lower eGFR and more diabetes-related comorbidities.</p><p><strong>Conclusion: </strong>yT2D have worse glycemic control, greater obesity, and similar renal decline compared with older adults with T2D. A high-risk subgroup of yT2D presents with a significantly lower eGFR. More research is needed to determine whether targeted therapy to high-risk groups will reduce diabetes-related complications.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 6","pages":"bvag100"},"PeriodicalIF":4.4,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13168882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147941884","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":"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":4.4,"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":"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":"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":4.4,"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":"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":"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":4.4,"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":"Pharmacodynamics of sustained levels of PTH following palopegteriparatide treatment in adults with hypoparathyroidism.","authors":"Aliya A Khan, Lars Rejnmark, Rajesh Jain, Susanne Pihl, Vibeke Miller Breinholt, Carol Zhao, Bryant Lai, Jenny Ukena, Christopher T Sibley, Aimee D Shu","doi":"10.1210/jendso/bvag098","DOIUrl":"10.1210/jendso/bvag098","url":null,"abstract":"<p><strong>Purpose: </strong>Palopegteriparatide is a prodrug of parathyroid hormone (PTH) (1-34), administered once daily. It is designed to provide active PTH within the physiologic range for 24 hours/day. The effects of palopegteriparatide on serum and urine markers were explored to determine if the pharmacodynamic profile of palopegteriparatide reflects continuous disease control in adults with hypoparathyroidism.</p><p><strong>Methods: </strong>A 24-hour sub-study was conducted during the PaTH Forward trial. Eligible participants were those who completed the Week 58 visit and received stable doses of palopegteriparatide for the prior week. Upon admission to the clinical research unit, participants received their usual dose of palopegteriparatide. Plasma PTH, serum calcium (albumin-adjusted), and serum phosphate concentrations were evaluated at 4-hour intervals. Urinary calcium, phosphate, and citrate concentrations were determined from each of six 4-hour collection periods. Descriptive statistics were performed.</p><p><strong>Results: </strong>Palopegteriparatide doses ranged from 12 to 33 µg/day and resulted in continuous exposure to active PTH within the estimated normal range over 24 hours. Mean serum calcium and serum phosphate were maintained near or within the normal ranges. Median urine calcium concentration was stable in the normal range for all 4-hour collection periods. Urine phosphate concentrations showed minor variability across collection intervals, and urine citrate was maintained above the lower limit of normal.</p><p><strong>Conclusion: </strong>Palopegteriparatide provided continuous exposure to active PTH within the physiological range. The expected pharmacodynamic effects of continuous PTH exposure on serum and urine chemistries were consistent with the efficacy and safety of palopegteriparatide demonstrated in the published PaTH Forward and PaTHway clinical trials.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 7","pages":"bvag098"},"PeriodicalIF":4.4,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13334101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148437035","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":"Estrogenic activity in tampon products.","authors":"Emma S Sutherland, Gihani Manodara, Ashley Gillon, Kelsey L Stevens, Alexia Kauff, Alison K Heather","doi":"10.1210/jendso/bvag094","DOIUrl":"10.1210/jendso/bvag094","url":null,"abstract":"<p><p>Tampons are widely used menstrual products with prolonged mucosal contact, raising questions about their potential role in exposing females to endocrine-disrupting chemicals (EDCs). This study evaluated estrogenic activity in tampon extracts using a cell-based estrogen receptor reporter bioassay. Synthetic and organic tampons sourced from domestic and international markets were tested for estrogenic bioactivity. Of the 18 brands analyzed, estrogenic activity was detected in nearly half, independent of material type. Comparative chemical analysis of one estrogenic-active brand vs one nonactive brand via high-resolution mass spectrometry tentatively identified various plasticizers, surfactants, and fragrance agents, that were present in higher concentrations in the estrogenic-active brand. The list of chemicals included known EDCs, such as phthalates and alkylphenols, that may be responsible for the observed estrogenic activity. Notably, estrogenic activity varied by brand, suggesting formulation-dependent risk. Although the detected in vitro activity levels were low, the findings demonstrate that compounds capable of activating estrogen receptors can leach from tampons. These results highlight the importance of including endocrine bioactivity assays in tampon safety assessments and suggest that safer formulations are achievable. Further investigation is warranted to assess long-term health implications of low-level EDC exposure from menstrual products.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 6","pages":"bvag094"},"PeriodicalIF":4.4,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13155100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147868644","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":"Effects of saccharin on insulin sensitivity in adult, overweight individuals without diabetes: a real-world pilot study.","authors":"Kenny Kalin, Karin Rådholm, Lisa Olsson, Valentina Tremaroli, Mark Woodward, Maria Wennberg, Fredrik Bäckhed, Olov Rolandsson","doi":"10.1210/jendso/bvag096","DOIUrl":"10.1210/jendso/bvag096","url":null,"abstract":"<p><strong>Context: </strong>It has been suggested that consumption of saccharin, a widely used artificial sweetener, decreases insulin sensitivity in rodents and humans, but studies show conflicting results.</p><p><strong>Objective: </strong>To investigate if saccharin affects insulin sensitivity in a proof-of-concept study in humans using hyperinsulinemic-euglycemic clamp.</p><p><strong>Methods: </strong>In an open-label pilot study, we recruited 14 overweight participants without diabetes who were mean 60.5 (SD 4.1) years of age and had a body mass index of 27.6 (SD 0.7). Insulin sensitivity, assessed by hyperinsulinemic-euglycemic clamp, was determined before and after consumption of 5 mg/kg saccharin/day for 3 months. Blood was collected for analysis of diabetes-related biomarkers. Stool samples were collected before, during, and after saccharin consumption for microbiota profiling by 16S rRNA gene sequencing.</p><p><strong>Results: </strong>Thirteen of the 14 participants (6 men, 7 women) completed the study. There was no change in insulin sensitivity (mean M value difference [ΔM] -0.1, <i>P</i> = .85) or body weight (mean difference -0.1 kg, <i>P</i> = .70) after consumption of saccharin. However, the mean glycated hemoglobin decreased from 38.7 mmol/mol (SD 3.0) at visit 1 to 36.8 (SD 3.4) at visit 4 (<i>P</i> = .003). Overall, there was no change in composition or richness of the gut microbiota at the end of the study.</p><p><strong>Conclusion: </strong>This study did not demonstrate an association between saccharin intake and impaired insulin sensitivity in adult, overweight participants without diabetes assessed by hyperinsulinemic-euglycemic clamp.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 6","pages":"bvag096"},"PeriodicalIF":4.4,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13166871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147930803","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":"Clinical and genetic characteristics of head and neck paragangliomas from China featuring Sino-European comparisons.","authors":"Jun Liu, Yingxian Pang, Jianing Yue, Yanting Shen, Jing Zhang, Minghao Li, Xiaowen Xu, Bin Chen, Jue Yang, Daqiao Guo, Jing Wang, Henri J L M Timmers, Christina Pamporaki, Henricus P M Kunst, Longfei Liu, Zhiqiang Lu, Zhiyin Zhang, Susan Richter, Jingjing Jiang","doi":"10.1210/jendso/bvag062","DOIUrl":"10.1210/jendso/bvag062","url":null,"abstract":"<p><strong>Context: </strong>Head and neck paragangliomas (HNPGLs) are tumors of parasympathetic origin, predominantly associated with pseudohypoxia and pathogenic variants (PVs) in succinate dehydrogenase (SDH) subunits, mainly based on studies in Europeans/Americans.</p><p><strong>Objective: </strong>This work aimed to assess the genetics of HNPGLs in a large Chinese cohort and compare them with European cases.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted of HNPGLs from 2 Chinese tertiary-care centers and 2 European centers. Participants included 222 Chinese and 205 European HNPGL patients. Main outcome measures included clinical presentation and genetic status assessed via next-generation sequencing of tumor/blood samples.</p><p><strong>Results: </strong>The Chinese HNPGL cohort consisted mainly of carotid body HNPGLs (86.9%), fewer jugulotympanic (12.2%), and no vagal HNPGLs. Jugulotympanic HNPGLs showed higher recurrence than carotid body HNPGLs (30.4% vs 8.5%; <i>P</i> = .009). PVs were detected in 62.2% of Chinese patients, predominantly in <i>SDHx</i> genes. PV frequency was higher in carotid body than jugulotympanic HNPGLs (65.8% vs 37%; <i>P</i> = .004), and in more male than female patients (75.9% vs 54.0%; <i>P</i> = .001). Compared to those without <i>SDHx</i> PVs, <i>SDHx</i> PVs carriers were younger (41.0 vs 49.0; <i>P</i> < .001), with more multifocal tumors (20.8% vs 7.6%; <i>P</i> = .007) and less often female (53.1% vs 76.1%; <i>P</i> < .001). Compared with Europeans, Chinese patients were younger (45.0 vs 54.3; <i>P</i> < .001), with fewer multilocal HNPGLs (0.9 vs 13.7%; <i>P</i> < .001), lower rates of recurrence (13.7% vs 28.0%; <i>P</i> = .007), but similar metastasis rates (3.9% vs 5.0%; <i>P</i> = .668).</p><p><strong>Conclusion: </strong>This is the first report of HNPGLs in a large Chinese cohort. Clinical presentation and practice as well as ancestry all likely contribute to the differences observed between Chinese and European patients.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 5","pages":"bvag062"},"PeriodicalIF":4.4,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13079993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147699109","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":"<i>SDHB</i>-associated paraganglioma in Saudi Arabia: High metastatic risk linked to a likely founder mutation.","authors":"Ali S Alzahrani, Balgees Alghamdi, Allianah Benito, Gamal Mohamed","doi":"10.1210/jendso/bvag070","DOIUrl":"10.1210/jendso/bvag070","url":null,"abstract":"<p><strong>Context: </strong><i>SDHB</i>-related pheochromocytoma and paraganglioma (PPGL) are associated with a high risk of metastasis. Minimal data are available on these genetically based tumors from the Middle East.</p><p><strong>Objective: </strong>To characterize the phenotype, genotype, and outcome of <i>SDHB</i>-associated PPGLs in Saudi Arabia.</p><p><strong>Methods: </strong>We retrospectively reviewed a cohort of 37 patients with <i>SDHB</i>-associated PPGL. DNA was isolated from peripheral blood samples, and genetic testing was performed using whole-exome sequencing (WES) and confirmed by Sanger sequencing.</p><p><strong>Results: </strong>We identified 37 patients with <i>SDHB</i> mutations, including 14 (37.8%) females and 23 (62.2%) males, with a median age at diagnosis of 28 years (range, 6-49). Nineteen patients (51.4%) had a positive family history of PPGL, and 18 (48.6%) were apparently sporadic but tested positive for <i>SDHB</i> mutations. The most common presentation was hyperadrenergic symptoms (54%), and the most common tumor location was the upper abdomen (45.9%). The most common <i>SDHB</i> mutation (likely a founder mutation) was the truncating mutation c.268T>C (p.R90*), which occurred in 23/37 patients (62%). This mutation was associated with high rates of locally invasive and/or distant metastasis (56.5%) and mortality (21.7%). At a median follow-up of 7 years (IQR 3.5-15), only 10 patients (27%) achieved remission, 7 (18.9%) died due to PPGL, one patient died due to leukemia, and 19 patients (51.4%) continued to have evidence of locally invasive or metastatic disease.</p><p><strong>Conclusion: </strong>In this Middle Eastern cohort, <i>SDHB</i>-associated PPGLs were characterized by high rates of locally invasive or metastatic disease, frequently associated with a possible founder mutation (p.R90*), and substantial mortality.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 6","pages":"bvag070"},"PeriodicalIF":4.4,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13186189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147982208","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}