The Journal of clinical endocrinology and metabolism最新文献

{"title":"Skeletal muscle is a critical site of disrupted lipid metabolism in male hypogonadism: an in vivo interventional study.","authors":"Clare Miller, Leanne Cussen, Tara McDonnell, Marie McIlroy, Amar Agha, Catherine L Winder, Wanchang Lin, Warwick B Dunn, Jerome Coffey, Oleksandr Boychak, Brian O'Neill, Mark Sherlock, Michael W O'Reilly","doi":"10.1210/clinem/dgag432","DOIUrl":"https://doi.org/10.1210/clinem/dgag432","url":null,"abstract":"<p><strong>Context: </strong>Male hypogonadism is associated with adverse cardiometabolic outcomes, however tissue-specific metabolic mechanisms underlying this phenotype remain poorly characterised. Metabolomic profiling in hypogonadism to date has been confined to plasma, with limited insights into skeletal muscle.</p><p><strong>Objective: </strong>To characterise the impact of testosterone replacement therapy (TRT) and androgen deprivation (ADT) on the plasma and skeletal muscle metabolome.</p><p><strong>Design: </strong>Parallel prospective interventional studies examined men initiating TRT for organic hypogonadism (n=15) and ADT for prostate cancer (n=15). Participants underwent metabolic phenotyping, plasma sampling and vastus lateralis muscle biopsies pre and post intervention (6 months TRT; 3 months ADT), with untargeted metabolomic profiling of both tissues at each timepoint.</p><p><strong>Results: </strong>TRT significantly increased serum testosterone (p<0.001) and muscle mass (p<0.05); ADT significantly reduced serum testosterone (p<0.001) and muscle mass (p<0.05) while simultaneously increasing fat mass (p<0.05). TRT significantly altered a total of 118 plasma metabolites, reflecting predominant suppression of circulating lipid species, whereas ADT altered only two. In skeletal muscle, TRT perturbed 89 metabolites and was characterised by expansion of intramuscular lipid species, while ADT altered 109 metabolites, with predominant depletion of intramuscular lipid classes. Following TRT, eight lipid classes showed divergent responses between plasma and skeletal muscle. In skeletal muscle, nine lipid classes responded differentially to TRT and ADT, including fatty acids, triacylglycerides and ceramides.</p><p><strong>Conclusion: </strong>This study provides the first untargeted metabolomic characterisation of skeletal muscle in response to androgen manipulation in humans. Distinct plasma and skeletal muscle responses demonstrate tissue-specific regulation that is incompletely captured by plasma profiling alone. These findings highlight skeletal muscle as a key site of androgen-sensitive metabolic regulation, providing evidence for tissue-specific lipid partitioning that may contribute to the cardiometabolic consequences of hypogonadism.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149241173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tests of the testes: markers of testicular function after treatment for pediatric hematological malignancies.","authors":"Harry J Hirsch","doi":"10.1210/clinem/dgag429","DOIUrl":"https://doi.org/10.1210/clinem/dgag429","url":null,"abstract":"","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149241166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulation of Growth Hormone Axis after Roux-en-Y Gastric Bypass.","authors":"Lei Pei, Cameron Cummings, Hamayle Saeed, Alessandra Amore, Maryam Farahmandsadr, Amanda Sheehan, Rafael Ferraz-Bannitz, Donald C Simonson, Mary-Elizabeth Patti","doi":"10.1210/clinem/dgag428","DOIUrl":"https://doi.org/10.1210/clinem/dgag428","url":null,"abstract":"<p><strong>Context: </strong>Bariatric metabolic surgery has potent effects on glucose metabolism, with increases in insulin sensitivity and insulin secretion contributing to both improved glycemia and/or remission of type 2 diabetes (T2D) and development of hypoglycemia (post-bariatric hypoglycemia, PBH). Previous studies suggest GH secretion and/or action are altered after bariatric surgery and may mediate early post-surgical improvements in glycemic control. Given the importance of GH signaling in glucose metabolism, we hypothesized that reductions in GH signaling and/or action could also contribute to PBH.</p><p><strong>Objective: </strong>Assessment of GH responses to two distinct stimuli: (1) experimental hypoglycemia induced by hyperinsulinemic hypoglycemic clamp and (2) glucagon stimulation.</p><p><strong>Setting: </strong>Academic medical center.</p><p><strong>Participants: </strong>Individuals with history of Roux-en-Y gastric bypass (RYGB) with PBH (n=20), without hypoglycemia (n=20), and weight-matched non-surgical controls (n=10).</p><p><strong>Main outcomes: </strong>GH responses were assessed (1) during experimental hypoglycemia and (2) after glucagon stimulation. Plasma GH receptor (GHR) and insulin-like growth factors and binding proteins were also measured.</p><p><strong>Results: </strong>Glucagon-stimulated GH levels were 5-6 times higher in both post-RYGB groups vs. controls at 120 minutes: control: 481±137 pg/ml; RYGB non-hypo 2521 ± 678 pg/ml; PBH: 3018 ±137pg/ml (control vs RYGB non-hypo p=0.02; control vs PBH; p=0.005). In contrast, PBH participants showed lower GH responses to experimental hypoglycemia. Additionally, plasma GHR and IGF-1 levels were reduced in PBH vs. controls.</p><p><strong>Conclusions: </strong>We find that plasma GH response to 2 distinct experimental stimuli differed in participants with a history of bariatric surgery. However, these patterns did not differ in those with and without PBH. Further studies will be required to determine if tissue-level alterations in GH action contribute to improved glycemic control after bariatric surgery.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149241169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of setmelanotide on metabolic syndrome risk in patients with proopiomelanocortin or leptin receptor deficiencies.","authors":"Martin Wabitsch, I Sadaf Farooqi, Wendy K Chung, Erica van den Akker, Peter Kühnen, James Swain, Jill C Garrison, Nicolas Touchot, Jesús Argente, Karine Clément","doi":"10.1210/clinem/dgag345","DOIUrl":"https://doi.org/10.1210/clinem/dgag345","url":null,"abstract":"<p><strong>Introduction: </strong>Patients with severe obesity due to proopiomelanocortin (POMC) or leptin receptor (LEPR) deficiencies resulting in impaired melanocortin-4 receptor (MC4R) signaling may be at risk for obesity-related comorbidities. Here, we report metabolic parameters and metabolic syndrome severity in patients before and after treatment with the MC4R agonist setmelanotide.</p><p><strong>Methods: </strong>Patients from phase 3 studies of setmelanotide for POMC (NCT02896192) or LEPR (NCT03287960) deficiencies with complete metabolic parameter data were included in this analysis. Metabolic parameters and metabolic severity Z scores based on body mass index (MetS-Z-BMI scores) were reported at baseline and following ∼1 year of setmelanotide treatment in these patients; subgroup analyses were conducted by sex, age, genotype, and response to treatment.</p><p><strong>Results: </strong>Metabolic parameters were evaluated in 18 of 21 patients enrolled in phase 3 trials. Group means for most parameters were within the normal range at baseline, excluding weight-related measures, fasting glucose, and triglycerides. The overall baseline mean (standard deviation [SD]) MetS-Z-BMI score was 1.49 (1.33). Most patients saw improvement in ≥1 metabolic parameter at week 52. The overall mean (SD) change in MetS-Z-BMI score after ∼1 year of treatment was -1.05 (0.88). Among subgroup analyses, MetS-Z-BMI score reductions were significantly greater in achievers of weight-based thresholds compared with nonachievers (P = .0187) and in patients with deficiencies in POMC compared with LEPR (P = .0278).</p><p><strong>Conclusion: </strong>Setmelanotide was associated with a reduction in specific metabolic parameters and metabolic syndrome severity (MetS-Z-BMI scores) in patients with POMC or LEPR deficiencies.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the Editor from Latupeirissa et al: \"Maternal TSH-receptor antibodies predict fetal/neonatal hyperthyroidism in pregnancies with a history of Graves disease\".","authors":"K M Latupeirissa, A Boelen, E Bruinstroop, J J Hillebrand, N KoK, A S van Trotsenburg, N Zwaveling-Soonawala, A C Heijboer","doi":"10.1210/clinem/dgag427","DOIUrl":"https://doi.org/10.1210/clinem/dgag427","url":null,"abstract":"","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149221329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"12,13-diHOME Is Increased During Targeted Temperature Management And Correlates With Survival After Cardiac Arrest Resuscitation.","authors":"Carolina Cora, Teresa L May, Breanna Page, Rika Goto, Margaret Mahoney, Ryan Reno Ba, James Reilly, Vlada Chekirka, Joanne T deKay, Mary S Weatherbee, Patience Mudjgiwa, Juan J Aristizabal-Henao, Michael A Kiebish, David Gagnon, Richard Riker, Sergey Ryzhov, David B Seder, Matthew D Lynes","doi":"10.1210/clinem/dgag415","DOIUrl":"https://doi.org/10.1210/clinem/dgag415","url":null,"abstract":"<p><strong>Context: </strong>Trials of targeted temperature management (TTM) after cardiac arrest (CA) have had conflicting results. Brown adipose tissue (BAT) is a thermogenic organ activated by cold temperature to regulate body temperature, systemic metabolism and the immune system. Approximately 10-30% of adult patients have BAT and this heterogeneity may explain variable treatment to TTM.</p><p><strong>Objective: </strong>This study sought to measure differences in outcome, metabolic and immune activation between patients treated with TTM following CA with varying BAT activity, measured through BAT-associated lipid 12,13-diHOME concentrations in circulation.</p><p><strong>Design: </strong>BAT biomarker 12,13-diHOME was quantified using liquid chromatography-mass spectrometry (LC-MS) on plasma from 74 patients at various time points starting at 6 hours and up until 7 days after return of spontaneous circulation (ROSC). Additionally, circulating glucose, C-peptide and fatty acids were measured by glucometer, ELISA and LC-MS, respectively. Peripheral blood mononuclear cells were analyzed by flow cytometry.</p><p><strong>Results: </strong>12,13-diHOME was increased in patients treated with TTM at 33°C and positively correlated with favorable outcomes. 12,13-diHOME levels peaked in the first 12 to 48 hours and decreased below the first post-ROSC level by 7 days. Glucose homeostasis was not associated with 12,13-diHOME levels. In a subset of patients, we could detect a specific phospholipid signature in patients with higher 12,13-diHOME. Patients with higher 12,13-diHOME also had increased mature neutrophils and lower immature neutrophils.</p><p><strong>Conclusions: </strong>Circulating 12,13-diHOME levels are increased in some patients undergoing targeted temperature management after cardiac arrest, which may be indicative of increased BAT activity. 12,13-diHOME is associated with survival, alterations of phospholipid metabolism, and a profile of less activated immune system. BAT may mediate the effects of temperature management on outcome after cardiac arrest.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum androgen profile of elite athletes.","authors":"David J Handelsman, Stephane Bermon","doi":"10.1210/clinem/dgag196","DOIUrl":"10.1210/clinem/dgag196","url":null,"abstract":"<p><strong>Introduction: </strong>The binary sex classification protects elite female athletes from the male physical advantages arising from puberty; however, mutations causing XY disorders of sex development (DSD) challenge the binary sex classification. Hormonal features of the most frequent XY DSDs in sports, androgen insensitivity syndrome (AIS) and 5α-reductase type 2 deficiency (5ARD) are not well described.</p><p><strong>Aims: </strong>To define serum androgen profiles in elite athletics (track and field) events.</p><p><strong>Methods: </strong>Serum samples from elite athletes (n = 1689; male 889, female 800; n = 5516 samples, median 3 per person) were analyzed by liquid chromatography-mass spectrometry (LCMS) for serum testosterone (T), dihydrotestosterone (DHT), and androstenedione in 19 World Anti-Doping Agency (WADA)-accredited laboratories. Serum steroids and ratios were analyzed by linear mixed model for repeated measures with adjustment for multiple comparisons and imputation for left-censored (dihydrotestosterone [DHT]) data. Among females, XY DSD identified by adult male serum T concentrations, had clinical diagnosis of 5ARD, AIS, or unclassified (UNCL).</p><p><strong>Results: </strong>XY DSD comprised 12 individuals with 5ARD with 2 with AIS (1 complete). Excluding pregnancy or androgen doping samples, men had higher serum T (n = 2671, 19.7 ± 0.1 nmol/L) and T/DHT ratio (n = 1903, 14.4 ± 0.2) than women (n = 2793, 1.1 ± 0.1 nmol/L; n = 1809, 3.7 ± 0.12, respectively) with XY DSD featuring male-like results (n = 52, 28.9 ± 0.8 nmol/L; n = 39; 32.0 ± 1.3).</p><p><strong>Conclusion: </strong>The prevalence of XY DSD in elite female athletes greatly exceeds that of the community with a high proportion of androgen-sensitive 5ARD. Serum T/DHT ratio by LCMS to characterize 5ARD can be extended to elite athletes.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"3262-3268"},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147849365","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":"Comprehensive analysis of disease spectrum and mortality in Sanjad-Sakati syndrome: an international rare disease registry study.","authors":"Angham Almutair, Katharina Karas, Abdulmajeed Al Subaihin, Omar Al Dibasi, Maali Melha, Hadeel Al-Ghamdi, Bijesh Yadav, Suliman Al Ghanam, Aisha Alanazi, Abdulaziz AlSaedi, Enad Althobaiti, Aisha Al Senani, Hanan Al Azkawi, Ayed Al Enezi, Ayman Bakkar, Ahmed Ali, Fahad Al Juraibah, Saif Alyaarubi, Afaf Al Sagheir, Wolfgang Högler","doi":"10.1210/clinem/dgag226","DOIUrl":"10.1210/clinem/dgag226","url":null,"abstract":"<p><strong>Context: </strong>Sanjad-Sakati syndrome (SSS), also known as hypoparathyroidism-intellectual disability-dysmorphism syndrome, is a rare autosomal recessive disorder caused by a TBCE founder mutation. The full disease spectrum remains poorly understood.</p><p><strong>Objectives: </strong>To comprehensively analyze growth, phenotype, endocrine manifestations, and mortality in a large multicenter SSS cohort.</p><p><strong>Methods: </strong>Clinical and genetic data were collected from 135 individuals across centers in the Gulf region using a REDCap survey.</p><p><strong>Results: </strong>The median age at inclusion was 9.1 years (range: birth-30 years; 50.3% female). The homozygous TBCE founder mutation (c.155_166del; p.Ser52_Gly55del) was detected in all genetically tested individuals (n = 68). Intrauterine growth restriction (mean birth weight -3.0 SD, length -3.3 SD) and dysmorphic features were universal. Postnatal growth showed severe failure to thrive during infancy, followed by persistently low height z-scores (-7 to -8). Endocrine features included hypoparathyroidism in all patients, primary hypothyroidism (16.5%), hypoglycemia (27.8%), nonautoimmune insulin-dependent diabetes (1.6%) and pituitary hormone deficiencies. Other findings included developmental delay (100%), hypocalcemic seizures (64.2%), tetany (53.3%), nephrocalcinosis (62.1%), gastroesophageal reflux (29.1%), and recurrent respiratory (63.7%) and bacterial infections (53.8%). Antibiotic prophylaxis was used in 35% of patients. Kaplan-Meier analysis estimated a median survival of 27.2 years, with respiratory failure causing 84% of deaths (21/25). The estimated overall survival at an age of 18 years was 62.4%.</p><p><strong>Conclusion: </strong>This largest reported SSS cohort highlights the high prevalence of associated endocrine, respiratory, and gastrointestinal manifestations, with respiratory failure as the leading cause of death. These data support the need for multidisciplinary care guidelines.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"3075-3084"},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148214219","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":"Ersodetug for refractory hypoglycemia due to malignant insulin-secreting tumors.","authors":"Jonathan Strosberg, Sean M Brown, Shagufta Shaheen, Marilyn Tan, Jairo Arturo Noreña, Armen I Yerevanian, Linda Lester, Leah M Wilson, Ole-Petter R Hamnvik, Johannes Hofland, Jasmine K Sidhu, Gopal Saha, Davelyn E Hood, Brian K Roberts, Jonathan M Dreyfuss, Mary-Elizabeth Patti","doi":"10.1210/clinem/dgag318","DOIUrl":"10.1210/clinem/dgag318","url":null,"abstract":"<p><strong>Background: </strong>Refractory hypoglycemia is common in malignant insulin-secreting tumors and is associated with substantial morbidity. Ersodetug is a fully human monoclonal antibody that allosterically attenuates insulin receptor signaling with the potential to treat various forms of hyperinsulinism (HI). We retrospectively report outcomes from compassionate use of ersodetug in 8 individuals with refractory hypoglycemia due to tumor HI.</p><p><strong>Methods: </strong>Ersodetug was administered intravenously at 6 or 9 mg/kg every 1-2 weeks initially, followed by a frequency of every 2-5 weeks, as appropriate. Glycemic, functional, and safety outcomes were analyzed.</p><p><strong>Results: </strong>Eight adults (4M/4F; 24-74 years; Eastern Cooperative Oncology Group [ECOG] 1-3) received ersodetug for insulin-secreting tumors (metastatic insulinoma, n = 7; cervical neuroendocrine carcinoma, n = 1). No drug-related serious adverse events were observed. Most patients experienced improved glycemic control, including discontinuation of parenteral glucose in 6 of the 7 applicable patients (median, 4.5 days) and a 35.6% relative reduction from baseline in time in hypoglycemia (<70 mg/dL) by continuous glucose monitoring (mean 12.4-8.0%; pseudo-median paired change of -3.8 percentage points [90% CI, -8.2 to -1.1]; P = .02). These glycemic improvements permitted hospital discharge and reductions in other antihypoglycemic therapies beyond glucose infusion rate (pseudo-median change, -2.5; 90% CI, -3.5 to -1.0; P = .02), with associated improvements in ECOG status. The median treatment duration with ersodetug (11.5 months, range 5-17) tended to correspond to patient lifespan in the setting of metastatic disease.</p><p><strong>Conclusion: </strong>Ersodetug therapy resulted in reduced hypoglycemia burden, ability to discontinue parenteral glucose infusion, allowing discharge from hospital, use of fewer antihypoglycemic therapies, and improved ECOG performance status in individuals with severe, refractory tumor HI.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"e2382-e2391"},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148682032","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":"Sleeve gastrectomy in pediatric and transition age patients with Prader-Willi syndrome: a 5-year longitudinal study.","authors":"Alessia Aureli, Francesco Carlomagno, Antonino Crinò, Sarah Bocchini, Sonia Battaglia, Daniela Camanni, Emanuela Ceriati, Michela Mariani, Stefano Delli Noci, Melania Manco, Francesco De Peppo, Andrea M Isidori, Stefano Cianfarani, Danilo Fintini","doi":"10.1210/clinem/dgag210","DOIUrl":"10.1210/clinem/dgag210","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the long-term effectiveness of laparoscopic sleeve gastrectomy (LSG) in pediatric and transition age patients with Prader-Willi syndrome (PWS).</p><p><strong>Design: </strong>Single-center, longitudinal, retrospective cohort study.</p><p><strong>Methods: </strong>We reviewed the electronic health records of 110 patients with PWS and 268 subjects undergoing LSG. We included 16 patients with PWS and severe obesity (PWS-LSG) and 32 matched non-syndromic patients with obesity (OB-LSG), both undergoing LSG, and 16 patients with PWS receiving lifestyle intervention only (PWS-LS). The primary endpoint was ΔBMI-SDS% at 5 years.</p><p><strong>Results: </strong>In PWS-LSG, BMI-SDS decreased from 5.18 to an early nadir at 1-2 years (median ΔBMI-SDS% ∼-26%), then partially rebounded to 4.75 at 5 years, with ΔBMI-SDS% -16.9% (P = .012). Conventional metrics confirmed this attenuated response, with %BMI change -2.8% and absolute ΔBMI-SDS -1.10 at 5 years. In OB-LSG, BMI-SDS declined from 4.95 to 2.24, with larger and more sustained improvement (ΔBMI-SDS% -57.4%; P < .001 within-group; P = .002 vs PWS-LSG), corresponding to a %BMI change -40.1% and absolute ΔBMI-SDS -2.81 at 5 years. In PWS-LS, BMI-SDS increased from 2.25 to 3.19 (ΔBMI-SDS% + 36.4%, P = .003). The mean number of obesity-related comorbidities decreased in PWS-LSG (2.69 ± 1.66 to 1.94 ± 1.18; P = .041) and in OB-LSG (1.25 ± 0.88 to 0.56 ± 0.76; P < .001), but increased in PWS-LS (1.56 ± 0.96 to 2.44 ± 1.32; P = .004).</p><p><strong>Conclusion: </strong>In PWS, LSG produces clinically relevant early weight loss with partial maintenance at 5 years, but markedly attenuated long-term benefit compared with non-syndromic peers. Nevertheless, when interpreted against the progressive worsening of obesity and cardiometabolic comorbidities observed with lifestyle intervention alone, LSG appears to modify disease trajectory in PWS.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"3143-3153"},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148020495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}