The Journal of clinical endocrinology and metabolism最新文献

{"title":"Debate About the Free Testosterone Hypothesis: Useful Tool or Misguided Mirage?","authors":"Bradley D Anawalt, David J Handelsman","doi":"10.1210/clinem/dgaf370","DOIUrl":"10.1210/clinem/dgaf370","url":null,"abstract":"<p><p>In this debate, 2 clinicians discuss the merits and demerits of the free testosterone hypothesis. Although most clinical guidelines recommend the measurement of free testosterone in the evaluation for male hypogonadism (at least in men with suspected low serum sex hormone-binding globulin), there remains controversy about the underlying hypothesis that serum free testosterone is a significant contributor to androgen effect. In this debate, Dr. Anawalt presents evidence to support the free testosterone hypothesis and advocates for the usefulness of accurate assessment of free testosterone in the evaluation of male hypogonadism. Dr. Handelsman argues that the evidence is unconvincing, the hypothesis is flawed and biologically invalid, and free testosterone cannot be accurately assessed in clinical practice.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"e3536-e3540"},"PeriodicalIF":5.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532928","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":"Correction to: \"The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline\".","authors":"","doi":"10.1210/clinem/dgaf445","DOIUrl":"10.1210/clinem/dgaf445","url":null,"abstract":"","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"e3549"},"PeriodicalIF":5.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144839940","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":"Response to Letter to the Editor From Raschi et al: \"Endocrine Adverse Reactions of Tyrosine Kinase Inhibitors in Combination With Immune Checkpoint Inhibitors\".","authors":"Wen Shao, Kaiwei Yang, Difei Lu, Ying Gao, Junqing Zhang, Yang Zhang","doi":"10.1210/clinem/dgaf344","DOIUrl":"10.1210/clinem/dgaf344","url":null,"abstract":"","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"e3545-e3546"},"PeriodicalIF":5.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304399","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 Raschi et al: \"Endocrine Adverse Reactions of Tyrosine Kinase Inhibitors in Combination With Immune Checkpoint Inhibitors\".","authors":"Emanuel Raschi, Monia Donati, Francesco Salvo, Charles Khouri","doi":"10.1210/clinem/dgaf343","DOIUrl":"10.1210/clinem/dgaf343","url":null,"abstract":"","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"e3541-e3542"},"PeriodicalIF":5.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304398","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":"Efficacy of GLP-1-based Therapies on Metabolic Dysfunction-associated Steatotic Liver Disease and Metabolic Dysfunction-associated Steatohepatitis: A Systematic Review and Meta-analysis.","authors":"Yahao Wang, Yue Zhou, Zhihong Wang, Yunzhi Ni, Gerald J Prud'homme, Qinghua Wang","doi":"10.1210/clinem/dgaf336","DOIUrl":"10.1210/clinem/dgaf336","url":null,"abstract":"<p><strong>Objective: </strong>New therapies are urgently needed for the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). We conducted this systematic review and meta-analysis to evaluate the therapeutic effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on MASLD/MASH.</p><p><strong>Methods: </strong>We searched PubMed, Embase, and Cochrane Library databases to identify randomized controlled trials (RCTs) that compared GLP-1RAs with placebo or active agents with respect to the efficacy in patients with MASLD/MASH. The effects of GLP-1RAs on liver fat content (LFC) by imaging, liver histology, serum liver enzymes, and noninvasive fibrosis indexes [Fibrosis-4, nonalcoholic fatty liver disease fibrosis score, cytokeratin 18, procollagen III, and liver stiffness) were evaluated. Mean differences and risk ratios with 95% confidence intervals were pooled using a random-effect model.</p><p><strong>Results: </strong>Twenty-five RCTs involving 2600 patients who used GLP-1RAs including liraglutide, exenatide, dulaglutide, semaglutide, tirzepatide, efinopegdutide, survodutide, and retatrutide were included. Overall, GLP-1RAs treatment for a median of 24 weeks demonstrated a significant reduction in LFC by 5.21%, with retatrutide displaying the most obvious treatment effects. GLP-1RAs treatment induced significant histological improvements in steatosis, hepatocellular ballooning, and lobular inflammation but nonsignificantly improved fibrosis, with the evidence for tirzepatide more robust than that for semaglutide and liraglutide. GLP-1RAs treatment significantly decreased serum alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transferase compared with control. GLP-1RAs also significantly improved liver stiffness, with semaglutide displaying the most obvious treatment effect. No drug-related adverse effects involving the liver were observed.</p><p><strong>Conclusion: </strong>GLP-1RAs decreased liver fat deposition and improved histological steatosis, hepatocellular ballooning, and lobular inflammation, without worsening of fibrosis in MASLD and MASH.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"2964-2979"},"PeriodicalIF":5.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259944","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":"Correction to: \"Temple Syndrome: Comprehensive Clinical Study in Genetically Confirmed 60 Japanese Patients\".","authors":"","doi":"10.1210/clinem/dgaf398","DOIUrl":"10.1210/clinem/dgaf398","url":null,"abstract":"","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"e3555"},"PeriodicalIF":5.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144639607","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":"Incretin Receptor Agonism, Fat-free Mass, and Cardiorespiratory Fitness: A Narrative Review.","authors":"Zhenqi Liu, Nathan R Weeldreyer, Siddhartha S Angadi","doi":"10.1210/clinem/dgaf335","DOIUrl":"10.1210/clinem/dgaf335","url":null,"abstract":"<p><strong>Context: </strong>Individuals with obesity often exhibit low muscle quality and are at risk of reduced muscle mass and diminished cardiorespiratory fitness (CRF). Glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RA) and dual GLP-1 and glucose-dependent insulinotropic polypeptide receptor agonist (GLP-1/GIPRA) promote significant loss in adipose tissue but are also associated with notable reductions in fat-free mass (FFM). It is not yet understood how these drugs affect CRF, which is an independent predictor of all-cause and cardiovascular mortality.</p><p><strong>Evidence description: </strong>People with obesity frequently have low CRF, which is defined by the Fick principle-the product of cardiac output and peripheral oxygen extraction. Cardiovascular dysfunction and reduced muscle quality, due to lipid infiltration, relatively low muscle mass, and dysfunctional microvasculature, work in concert to affect the determinants of the Fick equation and cause low CRF in this population. Weight loss interventions, including GLP-1RAs and dual GLP-1/GIPRA, may improve these measures. However, recent trials show GLP-1RAs and dual GLP-1/GIPRA therapy accelerates FFM loss. Evidence indicates that approximately 25% to 40% of weight loss attributed to GLP-1RAs and dual GLP-1/GIPRA comes from FFM loss, a rate far exceeding the annual age-related decline of FFM in adults. While these therapies have revolutionized obesity and glycemic management by inducing significant weight loss, reducing blood glucose levels, and demonstrating cardiovascular benefits in individuals with or without type 2 diabetes, clinical studies have failed to show improvements in CRF, a critical determinant of long-term cardiovascular health, and the long-term implications of FFM loss in these individuals remain unknown.</p><p><strong>Conclusion: </strong>GLP-1RAs and dual GLP-1/GIPRA significantly reduce body weight and adiposity, along with a substantial FFM loss but with no clear evidence of CRF enhancement. Further research is needed to elucidate the complex interplay among GLP-1 and dual GLP-1/GIP receptor agonism, FFM, direct cardiovascular measures, and determinants of CRF to optimize clinical outcomes in obesity and type 2 diabetes.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"2709-2717"},"PeriodicalIF":5.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251924","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":"Overnight Dexamethasone Suppression Test: Enhanced Accuracy with Late-Afternoon Cortisol and Morning/Late-Afternoon ACTH.","authors":"Anuj Ban, Saba Samad Memon, Anurag Ranjan Lila, Manjiri Karlekar, Rohit Barnabas, Chethan Y, Anima Sharma, Aditya Phadte, Vijaya Sarathi, Tukaram Jamale, Nalini Shah, Tushar Bandgar","doi":"10.1210/clinem/dgaf513","DOIUrl":"https://doi.org/10.1210/clinem/dgaf513","url":null,"abstract":"<p><strong>Context: </strong>Overnight dexamethasone suppression test (ODST) is precise and highly sensitive; however, its specificity ranges from 80-90%.</p><p><strong>Objective: </strong>To assess whether late-afternoon ODS cortisol and morning/late-afternoon ODS ACTH measurements improve ODST accuracy.</p><p><strong>Methods: </strong>Prospective, single-centre study included healthy adults (n=60), combined oral contraceptive pill users (COCP, n=29), chronic kidney disease (CKD, n=29), treatment-naïve ACTH-dependent Cushing syndrome (A-CS, n=33), post-treatment Cushing Disease in remission (CD-R, n=23) or persistence (CD-P, n=31). Participants underwent the standard 1-mg dexamethasone suppression test; blood samples were collected at 8-9 AM for cortisol, ACTH, dexamethasone; and at 3-4 PM for cortisol and ACTH.</p><p><strong>Results: </strong>ODS 4-PM cortisol was significantly lower than 8-AM in healthy adults (p=0.003), COCP (p<0.001), CKD (p<0.001), and CD-R (p=0.001), while this difference was not significant in treatment-naïve A-CS and CD-P. ODS 8-AM and 4-PM cortisol (cut-off: 1.8 μg/dL) showed high specificity in healthy adults (95% and 100%), but its specificity was low in COCP (55% and 79%) and CKD (17% and 52%). ODS 8-AM and 4-PM ACTH (cut-off: 10 pg/mL) showed high specificity in healthy adults (95%, 100%), COCP (100%, 100%), and CKD (96.6%, 100%), with 100% sensitivity for diagnosing A-CS. The diagnostic accuracy of ODS 4-PM cortisol, ODS 8-AM ACTH and ODS 4-PM ACTH in differentiating CD-R from CD-P was 98.1%, 81.5% and 81.5%, respectively.</p><p><strong>Conclusion: </strong>Late-afternoon cortisol measurement is a novel modification which enhances ODST specificity. ACTH measurement was particularly useful in COCP and CKD. Before widespread integration in clinical practice, further validation is required.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093470","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":"Response to Letter to the Editor From Mauvais-Jarvis and Dhindsa: \"Approach to the Patient: Low Testosterone Concentrations in Men With Obesity\".","authors":"Christopher A Muir, Gary A Wittert, David J Handelsman","doi":"10.1210/clinem/dgaf334","DOIUrl":"10.1210/clinem/dgaf334","url":null,"abstract":"","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"e3547-e3548"},"PeriodicalIF":5.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236777","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":"Cardiomyopathy in Patients With Acromegaly - Not Truly a Concern Anymore?","authors":"Peter Wolf, Luigi Maione, Peter Kamenický, Philippe Chanson","doi":"10.1210/clinem/dgaf338","DOIUrl":"10.1210/clinem/dgaf338","url":null,"abstract":"<p><p>Acromegaly is associated with increased mortality rates if not adequately treated. Cardiovascular and metabolic comorbidities are highly prevalent and have long been considered the main cause of death among patients with acromegaly. However, substantial advances in GH/IGF-I-lowering treatment, together with increased awareness and optimized management of other risk factors, have led to major improvements in mortality rates in the 2-3 past decades. Here, we review the effects of chronic excessive GH/IGF-I production and the successful treatment of this condition on relevant classical cardiovascular risk factors and on morphological and functional changes in the heart and discuss differences in reported prevalence rates over time according to different imaging methodologies used. Although morphological alterations (ie, myocardial hypertrophy as well as increased atrial and ventricular volumes) are common in patients with acromegaly, overt clinically relevant dysfunction is rare. Valvular cardiac disease and arrhythmia are also reviewed. Clinically relevant cardiomyopathy is currently less common than previously estimated. Recent epidemiological studies have shown that the risk of heart failure is comparable to that of the general population after adjusting for biochemical disease control and other risk factors.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"2718-2728"},"PeriodicalIF":5.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251902","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}