The Journal of clinical endocrinology and metabolism最新文献

{"title":"Reproductive Hormones During Minipuberty Suggest Subtle Testicular Impairments in Boys With Hypospadias.","authors":"Tina L Leunbach, Andreas Ernst, Trine Holm Johannsen, Agnethe Berglund, Jakob Albrethsen, Hanne Frederiksen, Anders Juul, Yazan F Rawashdeh","doi":"10.1210/clinem/dgaf618","DOIUrl":"10.1210/clinem/dgaf618","url":null,"abstract":"<p><strong>Context: </strong>The ontogeny of hypospadias and its implications remain incompletely understood.</p><p><strong>Objective: </strong>To examine whether fetal outcomes and reproductive hormone concentrations in boys with hypospadias differ from reference standards during minipuberty.</p><p><strong>Design: </strong>Prospective cohort study (May 2021-January 2023).</p><p><strong>Setting: </strong>Tertiary hypospadias center.</p><p><strong>Patients: </strong>Infants presenting with hypospadias (n = 139), of whom 113 were enrolled following parental consent (median postnatal age: 0.28 years).</p><p><strong>Interventions: </strong>Examination of hypospadias grade, external masculinization score (EMS), placental and birth weight, and blood sampling (reproductive hormones).</p><p><strong>Main outcome measures: </strong>Fisher's exact test assessed gestational age (GA)-specific birth weight and placental centiles by hypospadias severity. GA-specific reproductive hormone concentrations were converted to SD scores (SDSs) according to an established reference standard for healthy Danish boys. The 1-sample Wilcoxon signed-rank test compared concentrations to 0 SDS.</p><p><strong>Results: </strong>Eighty-nine boys (79%) had distal hypospadias with a median EMS of 11 while median EMS was 9 in boys with proximal hypospadias. Birth weight and placental centiles were lower in boys with proximal hypospadias (P = .014 and P = .038). The median concentrations of FHS (0.83 SDS), testosterone (0.71 SDS), and free testosterone (0.83 SDS) were higher in boys with hypospadias compared to 0 SDS (P < .001). The median concentrations of inhibin B (-0.38 SDS), anti-Müllerian hormone (AMH) (-0.23 SDS), insulin-like factor 3 (INSL3) (-0.31 SDS), androstenedione (-0.52 SDS), and dehydroepiandrosterone sulfate (-0.50 SDS) were significantly lower. LH, SHBG, 17-hydroxyprogesterone, and dihydrotestosterone were not statistically different. Hormone SDS did not differ significantly by hypospadias severity.</p><p><strong>Conclusion: </strong>Hypospadias severity was significantly associated with birth and placental weight centiles. Testicular Sertoli cell markers (AMH and inhibin B) and the Leydig cell-derived INSL3 were reduced, suggesting subtle testicular dysfunction in boys with hypospadias during minipuberty. Further research to identify implications for future reproductive health is warranted.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"1329-1336"},"PeriodicalIF":5.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145508289","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":"Brown Adipose Tissue and Metabolic Markers Differ Between Greenlanders and Danes With Cold Activation.","authors":"Mette Motzfeldt Jensen, Charlotte Elberling Almasi, Benedict Kjærgaard, Bodil Steen Rasmussen, Mette Korre Andersen, Mikkel Schubert, Torben Hansen, Christina Ellervik, Camilla Schéele, Marit Eika Jørgensen, Stig Andersen","doi":"10.1210/clinem/dgaf615","DOIUrl":"10.1210/clinem/dgaf615","url":null,"abstract":"<p><strong>Context: </strong>Brown adipose tissue (BAT) is a thermogenic tissue that converts energy into heat in response to cold exposure, and is therefore a promising target for improving cardiometabolic health. Habitually cold-exposed Arctic people represent a unique model of metabolic adaptation to cold.</p><p><strong>Objective: </strong>We investigated cold-induced BAT activation in Greenlanders in comparison to Danes.</p><p><strong>Methods: </strong>A comparative crossover study was conducted of 13 Greenlanders and 11 Danes, with 2 experimental sessions conducted 2 weeks apart: A, a thermoneutral session; and B, a cooling session. BAT volume and activity were assessed using 2-deoxy-2-[18F]-fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) imaging. Serial measurement of metabolic markers associated with BAT activity was performed by blood sampling.</p><p><strong>Results: </strong>Both for Greenlanders and Danes, core temperature decreased 0.5 °C during cooling, and the volume of active BAT increased, yet with a higher increase in active BAT volume of 16 917% in Greenlanders compared to 4541% in Danes (P = .046). Marked differences in glucose levels were seen in Greenlanders and Danes in response to cooling (Danes: 0.30 mmol/L, P = .013; Greenlanders: 0.16 mmol/L, P = .12), insulin (Danes: 2.43 pmol/L, P = .32; Greenlanders: 6.65 pmol/L, P = .001), triglycerides (Danes: -0.59 mmol/L, P < .001; Greenlanders: -0.16 pmol/L, P = .21), and total cholesterol (Danes: 0.39 mmol/L, P < .001; Greenlanders: 0.02 mmol/L, P = .89).</p><p><strong>Conclusion: </strong>The larger increase in BAT activity in response to cooling and the dampened response in metabolic parameters in Greenlanders compared to Danes leads to a hypothesis of preparedness for rapid thermogenic response to cold exposure in populations with active BAT.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"e1331-e1342"},"PeriodicalIF":5.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13099225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145535125","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":"Metabolism and Type 2 Diabetes Across Life Stages in Klinefelter Syndrome: A Population-Based Cohort Study.","authors":"Simon Chang, Lars Pedersen, Anne Skakkebæk, Agnethe Berglund, Claus H Gravholt","doi":"10.1210/clinem/dgaf619","DOIUrl":"10.1210/clinem/dgaf619","url":null,"abstract":"<p><strong>Context: </strong>Klinefelter syndrome (KS) is underdiagnosed, undertreated, and associated with metabolic dysfunction.</p><p><strong>Objective: </strong>We compared incidences of metabolic disorders among men with KS, either undiagnosed (U-KS), diagnosed and untreated (D-KS), or treated with testosterone replacement therapy (T-KS).</p><p><strong>Methods: </strong>This was a national Danish registry-based study from January 1994 to December 2022. We computed hazard ratios (HR) for incidence and severity of metabolic disorders between risk set matched strata of U-KS, D-KS, and T-KS and male control individuals. We evaluated the effect of parenteral vs transdermal testosterone supplementation on incidence of metabolic disorders in T-KS, applying inverse probability weighting.</p><p><strong>Results: </strong>We included 508 age-matched strata of U-KS, D-KS, and T-KS, and included 46 241 male controls. Incidence of metabolic conditions was more than 2-fold increased in KS, including type 2 diabetes (HR 2.56 [1.85-3.44]). U-KS presented with the most severe metabolic phenotype, with more obesity and more late-stage diabetes complications compared with T-KS (HR 2.83 [1.33-6.02]). All-cause mortality following diagnosis of type 2 diabetes was increased in D-KS compared with controls (HR 1.77 [1.28-2.45]), but nondifferential for T-KS and controls (HR 1.30 [0.68-2.48]). We saw a pattern of less obesity and type 2 diabetes, but more hypertension and hypercholesterolemia, with parenteral vs transdermal testosterone supplementation in T-KS.</p><p><strong>Conclusion: </strong>The metabolic profile in men with KS is dependent on diagnosis and treatment status, with pronounced metabolic dysfunction in U-KS. Better diagnosis and treatment of KS are needed to alleviate metabolic dysfunction and improve survival in men with KS.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"1311-1318"},"PeriodicalIF":5.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13099193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145524986","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":"Response to Letter to the Editor from Ting and Chen: \"Impact of Growth-Promoting Therapies on Puberty, Growth, and Final Height in Classical 21-Hydroxylase Deficiency\".","authors":"Zehra Yavas Abali, Abdullah Bereket, Tulay Guran","doi":"10.1210/clinem/dgag029","DOIUrl":"10.1210/clinem/dgag029","url":null,"abstract":"","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"e1474-e1475"},"PeriodicalIF":5.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146230323","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":"RNF216 Variants Found in Patients With Dementia, Hypogonadotropic Hypogonadism, and Severe Ataxia Deregulate Autophagy.","authors":"Jacques Young, Inès Abdennebi, Marion Le Saëc, Françoise Magnin, Larbi Amazit, Peter Kamenický, Luigi Maione, Jérôme Bouligand, Isabelle Beau","doi":"10.1210/clinem/dgaf640","DOIUrl":"10.1210/clinem/dgaf640","url":null,"abstract":"<p><strong>Context: </strong>Hypogonadotropic hypogonadism (HH) with severe ataxia, impotence, and dementia has been reported in a handful of patients carrying RNF216 gene variants. However, the underlying molecular mechanism explaining this complex phenotype remains unclear to date. RNF216 encodes a \"RING-between-RING\"(RBR)-class E3 ubiquitin ligase. Among the targets of RNF216 is Beclin-1, a pivotal regulator of autophagy, particularly within the central nervous system.</p><p><strong>Objectives: </strong>(i) To assess the prevalence of RN216 mutations in a large cohort of patients with HH. (ii) To examine the impact on autophagy of identified RNF216 pathogenic variants.</p><p><strong>Methods: </strong>Exome analysis in a monocentric cohort of patients with HH. In vitro functional analysis of RNF216 variants in the regulation of autophagy and cell viability.</p><p><strong>Results: </strong>Among 1476 patients, we identified a unique NM_207111.4:c.2056C>T:p.(Arg686*) RNF216 variant in the homozygous state in one family with 2 affected patients presenting with HH associated with late-onset ataxia and dementia. We observed that in cells expressing this RNF216 variant, the regulation of autophagy was disrupted, indicating a loss-of-function effect. We demonstrated that inhibiting RNF216 expression decreased cell viability. Z-VAD, a pan-caspase inhibitor, did not protect cells from death, whereas 3-MA, an autophagy inhibitor, prevented cell death. Interestingly, we found that other RNF216 variants reported to be associated with this form of HH had a similar functional impact on autophagy.</p><p><strong>Conclusion: </strong>Our results suggest that alteration of RNF216 function leads to cell death through an autophagy-mediated mechanism which contributes to combined HH and ataxia and dementia in affected patients.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"1278-1286"},"PeriodicalIF":5.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145575208","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":"HMGCR and Rosuvastatin Regulates GLP-1 Secretion and Expression-A Translational Study.","authors":"Michael G Miskelly, Andreas Lindqvist, Amra Jujić, Alexander Hamilton, Elaine Cowan, Sweta Raikundalia, Anna-Maria Dutius Andersson, Bent J Nergård, Rita Del Giudice, Dmytro Kryvokhyzha, Peter M Nilsson, Jens Juul Holst, Signe Sørensen Torekov, Jens O Lagerstedt, Maria F Gomez, Lena Eliasson, Hindrik Mulder, Jan Hedenbro, Martin Magnusson, Nils Wierup","doi":"10.1210/clinem/dgaf608","DOIUrl":"10.1210/clinem/dgaf608","url":null,"abstract":"<p><strong>Context: </strong>Statin use is associated with increased risk of type 2 diabetes (T2D) and mild hyperglycemia. The underlying mechanisms are not well studied, and the effect of statin treatment on glucagon-like peptide 1 (GLP-1) secretion or production is unknown.</p><p><strong>Objective: </strong>This work aimed to assess the effects of rosuvastatin on GLP-1 secretion and production.</p><p><strong>Methods: </strong>We performed association studies in the Malmö Diet and Cancer study cardiovascular cohort (MDCS-CC) reexamination cohort, in vitro investigations using GLUTag cells and acute and chronic studies in female, normoglycemic C57Bl/6j mice.</p><p><strong>Results: </strong>Studies in the MDCS-CC reexamination cohort (n = 3734) revealed that in individuals without T2D, statin usage was associated with higher fasting glucose-dependent insulinotropic peptide (GIP), insulin, glucose, glucagon, and homeostatic model assessment of insulin resistance, but not GLP-1. However, in patients with T2D, statin usage was associated with higher fasting GLP-1 levels. Rosuvastatin treatment or 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (Hmgcr) knockdown (KD) reduced GLP-1 secretion and increased Gcg messenger RNA in GLUTag cells. Rosuvastatin acutely reduced postprandial GLP-1 secretion, whereas chronic rosuvastatin treatment in mice caused hyperglycemia and increased postprandial GLP-1 levels. The acute effect of Hmgcr KD on GLP-1 secretion could be mimicked by targeting intracellular cholesterol using a PCSK9 inhibitor. Finally, transcriptomic alterations induced by rosuvastatin were limited to genes involved in cholesterol biosynthesis.</p><p><strong>Conclusion: </strong>We have established HMGCR as a regulator of GLP-1 secretion and provide a plausible explanation for the clinically observed mild hyperglycemia associated with statin use. Given the negative acute effect on GLP-1 secretion, monitoring of blood glucose levels is recommended after prescribing rosuvastatin.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"e1343-e1355"},"PeriodicalIF":5.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13099218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145476706","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":"Altered Glucagon Response to Oral Glucose in Individuals at Different Stages of Type 1 Diabetes Development.","authors":"Helena Kontola, Luís Crisóstomo, Eliisa Löyttyniemi, Jaakko J Koskenniemi, Riitta Veijola, Jorma Toppari, Jukka Kero","doi":"10.1210/clinem/dgaf601","DOIUrl":"10.1210/clinem/dgaf601","url":null,"abstract":"<p><strong>Context: </strong>Autoimmune destruction of β cells and their functional decline precedes the clinical onset of type 1 diabetes. However, altered α-cell function and hyperglucagonemia may contribute to the development of hyperglycemia and ketoacidosis at onset.</p><p><strong>Objective: </strong>In this cross-sectional study, we analyzed glucagon concentrations during an oral glucose tolerance test (OGTT) in individuals at the early stages of type 1 diabetes to understand the role of α-cell function in the disease process.</p><p><strong>Methods: </strong>We recruited 47 participants, aged 4 to 25 years, from the Finnish Diabetes Prediction and Prevention (DIPP) study, and categorized them into the following groups: islet autoantibody (IAb) negative, single IAb positive, and stages 1 to 3 of type 1 diabetes. Glucagon levels were measured during a 6-point OGTT using a conventional radioimmunoassay, alongside insulin, C-peptide, glucose, and glucagon-like peptide-1 (GLP-1).</p><p><strong>Results: </strong>Fasting plasma glucagon levels increased with disease progression. The longitudinal patterns of glucagon concentrations during the OGTT differed significantly between groups, with a paradoxical 15-minute glucagon increase observed only in individuals at early stage 3 of type 1 diabetes.</p><p><strong>Conclusion: </strong>These findings highlight the need for prospective studies to further elucidate the role of α cells in disease progression and support testing pharmacotherapies aimed at improving both α- and β-cell functions during disease development.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"1431-1437"},"PeriodicalIF":5.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13099181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145423866","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":"Hair Mercury Levels, Serum n-3 Fatty Acids, and Pregnancy Glucose Outcomes Among Women From a Fertility Center.","authors":"Xinxiu Liang, Han Han, Xilin Shen, Paige L Williams, Tamarra James-Todd, Yazeed Allan, Roe P Keshet, Jennifer B Ford, Kathryn M Rexrode, Jorge E Chavarro, Russ Hauser, Lidia Mínguez-Alarcón","doi":"10.1210/clinem/dgaf594","DOIUrl":"10.1210/clinem/dgaf594","url":null,"abstract":"<p><strong>Background: </strong>Mercury (Hg) exposure has been linked to gestational diabetes mellitus, but findings are inconclusive. Fish, the main source of nonoccupational Hg exposure, is also rich in long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs), which may offer metabolic benefits. The joint impact of Hg and n-3 PUFAs on maternal glucose metabolism remains unclear.</p><p><strong>Objective: </strong>To examine the association between prepregnancy Hg exposure and glucose metabolism during pregnancy and evaluate whether serum eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) modify this relationship.</p><p><strong>Design: </strong>We included 430 women from the Environment and Reproductive Health Study with prepregnancy hair Hg and mid- to late-pregnancy glucose levels. Of these, 182 had prepregnancy serum EPA and DHA. Generalized linear models were used to assess associations of log-transformed Hg with glucose and impaired glucose tolerance (IGT). Stratified analyses were performed by EPA + DHA levels and prepregnancy body mass inde (BMI).</p><p><strong>Results: </strong>Higher Hg was associated with elevated glucose (per SD: β = 0.09, 95% confidence interval: 0.002-0.19) and 2.05-fold increased odds of IGT (Q4 vs Q1). Similar associations were observed among women with lower circulating EPA + DHA, and stronger associations were seen among those with prepregnancy BMI ≥25 kg/m2.</p><p><strong>Conclusion: </strong>Higher prepregnancy Hg exposure was associated with increased IGT odds, potentially modified by BMI and n-3 PUFA status.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"e1427-e1434"},"PeriodicalIF":5.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13040445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145403588","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":"Graves' disease: a new era of pathophysiology-guided therapeutics.","authors":"Marius N Stan, David Toro-Tobon","doi":"10.1210/clinem/dgag010","DOIUrl":"10.1210/clinem/dgag010","url":null,"abstract":"<p><p>Graves' disease (GD) is an autoimmune entity that had an unchanged treatment paradigm for more than half a century with radioactive iodine, antithyroid drugs (ATDs), and surgery representing the mainstay of therapy, with variation in their use over time and geographic location. Hypothyroidism has been an accepted tradeoff in many cases, though recently there are increased concerns about altered quality of life in these patients. Fortunately, the last decade has seen an intense pursuit of GD's immunological mechanisms and a recalibration of classic treatment modalities focusing on thyroid preservation, as reflected in the preference for ATD as primary therapy, including its use in long-term protocols. The immune targets currently explored aim to address this gap by intervening in the TRAb lifecycle: minimizing production (eg, B-cell targeting), enhancing clearance (eg, neonatal Fc receptor inhibitors), or neutralizing its target-the TSH receptor (eg, receptor blockade). While these approaches are going through the necessary clinical trials evaluation, we are starting to see the potential for technology and artificial intelligence to make an impact on how we identify, treat, and monitor patients with GD. The combination of these approaches will likely lead to a significant individualization of GD management that will take us from the goal of normalization of thyroid levels to that of inducing long-term remission and prevention of the associated autoimmune phenomena that GD is associated with. While time is needed for these aspects to mature, the future looks bright for our GD patients and maybe soon these lessons will open new doors for our patients with Hashimoto's thyroiditis as well.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"1212-1224"},"PeriodicalIF":5.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145968248","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":"Adolescent \"Lean PCOS\" Is Characterized by Higher Insulin Resistance and Adverse Adipokine Profile.","authors":"Rachel C Whooten, Sheryl L Rifas-Shiman, Izzuddin M Aris, Wei Perng, Jorge E Chavarro, Emily Oken, Marie-France Hivert","doi":"10.1210/clinem/dgaf606","DOIUrl":"10.1210/clinem/dgaf606","url":null,"abstract":"<p><strong>Objective: </strong>Although polycystic ovary syndrome (PCOS) is associated with high body mass index (BMI), less is known about the cardiometabolic manifestations of PCOS without excess adiposity. Among female adolescents enrolled in the Project Viva longitudinal prebirth cohort, we characterized growth, adiposity, and cardiometabolic biomarkers among those with vs without PCOS, stratified by BMI category.</p><p><strong>Methods: </strong>We defined PCOS at the mid-teen visit (mean age 17.7 years) as self-reported diagnosis or oligo-anovulation with clinical/biochemical hyperandrogenism. We obtained anthropometric and dual x-ray absorptiometry measurements. Within each BMI category (≥85th percentile vs < 85th percentile), we used unadjusted linear regression to compare growth trajectories, adiposity, and cardiometabolic biomarkers among those with vs without PCOS. We used mixed effects models to visually represent estimated BMI and linear growth trajectories.</p><p><strong>Results: </strong>Among 358 females with data at the mid-teen visit, n = 51 (14%) participants met our criteria for PCOS. Among females with BMI <85th percentile, those with PCOS (n = 27) had earlier age at peak height velocity [β = -.57 years; 95% confidence interval (CI) -0.96, -0.18], higher Homeostatic Model Assessment of Insulin Resistance (β = .77, 95% CI 0.23, 1.30), and lower adiponectin-leptin ratio (β = -.35, 95% CI -0.65, -0.06) vs without PCOS. Females with BMI ≥85th percentile had similar biomarkers by PCOS status. Adiposity measures did not differ by PCOS status within either BMI category.</p><p><strong>Conclusion: </strong>Within this population-based cohort, adolescents with PCOS and BMI <85th percentile had greater insulin resistance and adipose tissue dysfunction vs without PCOS. PCOS-associated metabolic dysfunction exist even among adolescents with BMI <85th percentile.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"e1364-e1372"},"PeriodicalIF":5.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12867335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145703742","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}