The Journal of clinical endocrinology and metabolism最新文献

{"title":"Post-transplant diabetes mellitus requiring insulin identifies high-risk outcomes after solid organ transplantation.","authors":"Rossana Caldara, Davide Catarinella, Chiara Gremizzi, Stefano Tentori, Vera Paloschi, Sarah Williford, Francesca Rusconi, Lorenzo Piemonti","doi":"10.1210/clinem/dgag217","DOIUrl":"10.1210/clinem/dgag217","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>Post-transplant diabetes mellitus (PTDM) is a common complication after solid organ transplantation, but its long-term prognostic significance and the clinical implications of post-transplant antidiabetic treatment patterns remain incompletely understood. We aimed to evaluate PTDM incidence, determinants, treatment patterns, and associated long-term outcomes using large-scale real-world data.</p><p><strong>Methods: </strong>We analyzed adult solid organ transplant recipients without preexisting diabetes within the TriNetX Global Collaborative Network (2006-2024). PTDM incidence and risk factors were assessed using time-to-event analyses. Clinical outcomes were evaluated using propensity score-matched cohorts. Antidiabetic treatment patterns were characterized using treatment pathway analyses and outcomes were compared according to insulin vs non-insulin-based management among recipients with PTDM.</p><p><strong>Results: </strong>Among 263 325 recipients, PTDM incidence increased over time and varied markedly by transplanted organ, transplant era, and geographic region. Older age, male sex, adiposity, baseline dysglycemia, dyslipidemia, reduced renal function, and immunosuppressive exposure were independently associated with PTDM. After matching, PTDM was associated with higher long-term risks of mortality, graft failure, graft rejection, cardiovascular events, infections, malignancies, and renal-metabolic complications, whereas early post-transplant risks were largely comparable. Antidiabetic treatment patterns were heterogeneous and organ-specific. Insulin-treated PTDM recipients experienced substantially worse graft and patient outcomes than non-insulin-treated recipients, despite similar long-term glycemic control, indicating that insulin requirement identifies a high-risk metabolic phenotype. Findings were consistent in single organ transplant-specific sensitivity analyses.</p><p><strong>Conclusion/interpretation: </strong>PTDM acts as a chronic modifier of long-term outcomes after solid organ transplantation. Insulin-treated PTDM identifies a subgroup at particularly high risk, underscoring the need for improved metabolic risk stratification and tailored management strategies in transplant recipients.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"3128-3142"},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148020498","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":"Retatrutide and lipid and metabolite profiles in participants with obesity with or without type 2 diabetes.","authors":"Mackenzie J Pearson, Jill A Willency, Yanzhu Lin, Arkan Abadi, Mark L Hartman, Tamer Coskun, Giacomo Ruotolo, Kevin L Duffin, Axel Haupt, Christopher B Newgard, Valentina Pirro","doi":"10.1210/clinem/dgag201","DOIUrl":"10.1210/clinem/dgag201","url":null,"abstract":"<p><strong>Context: </strong>In phase 2 trials, retatrutide reduced body weight, hemoglobin A1c and improved the lipid profiles of participants living with obesity, with and without T2D.</p><p><strong>Objective: </strong>Assess plasma metabolome and lipidome changes associated with retatrutide treatment.</p><p><strong>Methods: </strong>Metabolomics and lipidomics were performed in fasting samples from 2 randomized, placebo-controlled phase 2 trials as a post hoc exploratory analysis. Participants living with obesity with and without T2D were treated for 36 and 48 weeks, respectively. There were 282 and 213 participants in the obesity and T2D trials, respectively and the intervention(s) received were: Obesity trial: retatrutide (1, 4, 8, and 12 mg) or placebo; T2D trial: retatrutide (0.5, 4, 8, and 12 mg) or placebo or dulaglutide (1.5 mg). The main outcome measure(s) were changes in metabolite and lipid levels with retatrutide treatment against baseline levels and placebo using multiplicity correction.</p><p><strong>Results: </strong>At both primary and study endpoints for both populations, higher doses of retatrutide were associated with changes in a cluster of metabolites comprising 3-hydroxybutyrate, acetylcarnitine, free carnitine, and fatty acid-derived long-chain acylcarnitines. Mediation analyses suggested that changes in these biomarkers mediated 23.2% of the weight reduction response in participants without T2D and that this mediation was blunted to 12.7% in participants with T2D. Retatrutide treatment was also associated with changes in metabolites associated with insulin resistance, including branched-chain amino acids and their catabolic products, 2-aminoadipic acid, 2-hydroxybutyrate, urate, and triglycerides enriched in short-chain and saturated acyl side chains. These changes were found in both study populations and sustained across study endpoints.</p><p><strong>Conclusion: </strong>Retatrutide was associated with changes in 2 metabolic clusters related to fatty acid oxidation and insulin resistance in a direction associated with improved metabolic health and reduced cardiovascular risk.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"3217-3228"},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147944764","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 Chertok Shacham: \"Approach to the patient with thyroid storm\".","authors":"Peter A Kopp, Ilaria Giordani, Ulla Feldt-Rasmussen, Aurélie Forget-Renaud","doi":"10.1210/clinem/dgag305","DOIUrl":"10.1210/clinem/dgag305","url":null,"abstract":"","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"e2443-e2444"},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148633448","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: \"BRAF-induced EHF Expression Affects TERT in Aggressive Papillary Thyroid Cancer\".","authors":"","doi":"10.1210/clinem/dgag353","DOIUrl":"10.1210/clinem/dgag353","url":null,"abstract":"","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"e2445-e2447"},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148877068","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":"The extra X chromosome and autoimmune susceptibility in Klinefelter syndrome.","authors":"Elisa Gatta, Andrea Delbarba, Virginia Maltese, Caterina Buoso, Carlo Cappelli","doi":"10.1210/clinem/dgag268","DOIUrl":"10.1210/clinem/dgag268","url":null,"abstract":"<p><strong>Objective: </strong>To systematically evaluate and quantitatively synthesize the association between Klinefelter syndrome (KS) (47,XXY karyotype) and autoimmune susceptibility.</p><p><strong>Methods: </strong>PubMed/MEDLINE, Scopus, and Web of Science were systematically searched from database inception to April 30, 2026, for studies evaluating autoimmune diseases or autoimmune serological markers in individuals with KS. The protocol was registered in PROSPERO (CRD420261399097). Random-effects models were prespecified, summary data were extracted from published reports, and pooled effect estimates were expressed as odds ratios (ORs) with 95% CIs. Subgroup analyses were performed according to outcome definition (isolated autoantibody positivity vs clinically manifest autoimmune disease). Risk of bias was assessed using the Newcastle-Ottawa Scale.</p><p><strong>Results: </strong>Eight studies were included in the qualitative synthesis and six studies (8 datasets) in the quantitative analysis, comprising 2289 individuals with KS and 51 250 114 controls. KS was associated with markedly increased autoimmune susceptibility compared with control populations (OR 23.25, 95% CI 9.96-54.31), with moderate-to-substantial between-study heterogeneity (I2 = 66.4%). Associations were stronger for clinically manifest autoimmune diseases (OR 48.46, 95% CI 17.68-132.87) than for isolated autoantibody positivity (OR 9.99, 95% CI 1.18-84.77). The autoimmune spectrum predominantly involved female-predominant and interferon-associated disorders, including systemic lupus erythematosus, Sjögren syndrome, systemic sclerosis, autoimmune thyroid disease, and type 1 diabetes mellitus.</p><p><strong>Conclusion: </strong>KS is associated with increased autoimmune susceptibility, particularly for clinically overt autoimmune diseases. These findings support a potential contribution of sex chromosome complement to immune dysregulation and reinforce the importance of clinical awareness of autoimmune comorbidities in individuals with KS.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"3296-3305"},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148383537","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":"Cardiovascular effects of metyrapone treatment in patients with mild autonomous cortisol secretion: a secondary analysis.","authors":"Helena Niziolek, Ivica Just, Clemens Baumgartner, Anna Tosin, Hansjörg Habisch, Paul Fellinger, Hannes Beiglböck, Michael Poledniczek, Luise Bellach, Anton Luger, Alexandra Kautzky-Willer, Siegfried Trattnig, Maximilian Zeyda, Thomas Scherer, Marie Helene Schernthaner-Reiter, Florian W Kiefer, Greisa Vila, Andreas Kammerlander, Tobias Madl, Michael Leutner, Martin Krssak, Michael Krebs, Peter Wolf","doi":"10.1210/clinem/dgag228","DOIUrl":"10.1210/clinem/dgag228","url":null,"abstract":"<p><strong>Context: </strong>Mild autonomous cortisol secretion (MACS) is associated with increased mortality, mainly because of cardiovascular disease.</p><p><strong>Objective: </strong>Here we investigated the effects of cortisol-lowering medical treatment on blood pressure regulation, cardiac fat depots, heart function and morphology, and other cardiovascular risk factors.</p><p><strong>Methods: </strong>In this secondary analysis of our prospective, open-label, single-center study at the Medical University of Vienna, we investigated 15 patients with MACS (12 women; age 59 [53-64] years) before and after 12 weeks of treatment with evening doses of metyrapone (500 mg at 6 Pm and 250 mg at 10 Pm). Cardiac fat stores, morphology, and myocardial function were evaluated using cardiac magnetic resonance imaging and spectroscopy. Orthostatic blood pressure regulation was measured by standardized protocols. Lipidomics, renin-angiotensin-aldosterone-system activity and branched-chain amino acid (BCAA) concentrations were assessed.</p><p><strong>Results: </strong>Mean supine systolic (137 [121-139] vs 122 [115-129] mmHg; P = 0.041) and diastolic (89 [80-93] vs 75 [71-86] mmHg; P = .045) blood pressure decreased after treatment in patients without changes in concomitant antihypertensive medication. Epicardial fat was lower at follow-up compared to baseline (1032.70 [894.23-1482.90] vs 929.37 [736.12-1317.15] mm2; P = .022). No changes in paracardial and intramyocardial fat, as well as in cardiac function and morphology were observed. The aldosterone-to-angiotensin II ratio was lower at follow-up (1.56 [0.87-2.82] vs 1.21 [0.98-1.92]; P = .042) and alterations in lipid profiles, but not in BCAA levels, were identified.</p><p><strong>Conclusion: </strong>Treatment with evening doses of metyrapone improved blood pressure and reduced epicardial adipose tissue.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"3050-3061"},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148221664","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":"Approach to the patient with elevated lipoprotein(a).","authors":"Timothy McGinnis, David R Saxon","doi":"10.1210/clinem/dgag286","DOIUrl":"10.1210/clinem/dgag286","url":null,"abstract":"<p><p>Lipoprotein(a) [Lp(a)] is a common, genetically determined lipoprotein that is independently associated with myocardial infarction, stroke, peripheral artery disease, and calcific aortic stenosis. Because Lp(a) levels are stable over time and minimally influenced by lifestyle, the 2026 ACC/AHA/Multisociety Dyslipidemia Guideline now recommends one-time measurement in all adults and cascade screening in high-risk families; as a result, endocrinologists can expect to encounter and manage elevated Lp(a) frequently in routine clinical practice. Despite its clinical importance, no approved drug therapies specifically targeting Lp(a) yet exist; therefore, management should currently focus on aggressive optimization of traditional risk factors, particularly LDL-C lowering with statins and selective use of adjunctive therapies such as PCSK9 inhibitors and lipid apheresis. Emerging evidence suggests a potential benefit of selective aspirin use, while novel therapeutics-antisense oligonucleotides and small interfering RNAs-which robustly lower Lp(a) are currently being tested in phase 3 clinical trials. We present case-based examples to highlight practical approaches to risk assessment and management of elevated Lp(a).</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"3286-3295"},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148475677","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: \"Medical treatments for obesity: what does the future have in store?\"","authors":"","doi":"10.1210/clinem/dgag413","DOIUrl":"https://doi.org/10.1210/clinem/dgag413","url":null,"abstract":"","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":"149198860","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":"Parathyroid carcinoma: from molecular pathogenesis to multidisciplinary management.","authors":"Jia-Xi Song, Yu-Ying Yang, Jin-Xin Zhou, Jing Xie, Hao-Ji Gao, Min-Ting Zhu, Bei Tao, Xi Chen, Li-Hao Sun, Jian-Min Liu","doi":"10.1210/clinem/dgag266","DOIUrl":"10.1210/clinem/dgag266","url":null,"abstract":"<p><p>Parathyroid carcinoma (PC) is a rare malignancy accounting for <1% of primary hyperparathyroidism cases. This review summarizes current knowledge on its molecular pathogenesis, diagnosis, imaging, management and prognosis. PC is driven primarily by CDC73 mutations with loss of parafibromin expression, with emerging roles for PI3K/AKT/mTOR and Wnt pathway alterations. Its diagnosis remains challenging. Clinical suspicion should arise with marked hypercalcemia, elevated PTH, palpable neck mass or recurrent laryngeal nerve palsy. Imaging modalities including cervical ultrasound, 99mTc-sestamibi, 4D-CT, and [18F]fluorocholine PET/CT aid localization and metastasis detection. En bloc resection with ipsilateral thyroid lobectomy is the standard approach. Traditional medical therapies are helpful in reducing serum calcium level. Radiotherapy and chemotherapy have limited efficacy. Targeted therapies and immunotherapy show promise in advanced disease, however, the such evidence is weak. Recurrence rates of 23% to 65% mandate lifelong follow-up. Prognostic factors include surgical approach, postoperative remission, Ki-67 index, as well as parafibromin status and mTOR activation. Multidisciplinary management in specialized centers is critical for optimizing outcomes.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"3012-3031"},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148383544","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":"Medical treatments for obesity: what does the future have in store?","authors":"Aya Bassatne, Ivania Rizo","doi":"10.1210/clinem/dgag274","DOIUrl":"10.1210/clinem/dgag274","url":null,"abstract":"<p><strong>Context: </strong>Obesity is a chronic relapsing disease associated with substantial morbidity, mortality, and health care costs. Contemporary obesity pharmacotherapies extend beyond weight reduction, with evidence for improvements across multiple obesity-related complications, supporting a shift toward phenotype-guided, complication-centric care.</p><p><strong>Evidence acquisition: </strong>A systematic literature search of the Medline database using MeSH terms and keywords related to new-generation obesity pharmacotherapy was conducted to identify articles published between 2021 and 2026. Reference lists of relevant reviews were screened to identify additional eligible studies. Phase 2 and 3 clinical trials evaluating emerging obesity pharmacotherapies in adults and reporting outcomes, including weight loss and obesity-related complications, were included.</p><p><strong>Evidence synthesis: </strong>Entero-pancreatic hormone-based therapies targeting glucagon-Like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide, amylin, and glucagon pathways demonstrate substantial efficacy beyond weight reduction. These hormones act through complementary mechanisms regulating appetite, energy balance, and metabolic homeostasis. GLP-1 based agents achieve approximately 10-15% weight loss, whereas agents targeting multiple pathways demonstrate greater efficacy. Tirzepatide, CagriSema, and amycretin achieved weight reductions exceeding 20% and the triple agonist retatrutide produced reductions exceeding 25%. Beyond weight loss, these agents improve glycemia, support diabetes prevention, and produce organ-specific benefits, including reduced cardiovascular events, improved heart failure symptoms, decreased obstructive sleep apnea severity, improvement of metabolic dysfunction-associated steatohepatitis, slowing chronic kidney disease progression, and reduced osteoarthritis-related pain.</p><p><strong>Conclusion: </strong>Next-generation obesity pharmacotherapies represent a major advance in obesity management and support a treat-to-target approach prioritizing improvement in obesity-related complications and metabolic health. Effective implementation will require individualized therapy and attention to long-term safety, access, and equitable delivery of care.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"e2327-e2346"},"PeriodicalIF":5.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148440674","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}