Journal of Clinical Endocrinology & Metabolism最新文献

{"title":"The Risk of Adrenal Insufficiency After Treatment With Relatlimab in Combination With Nivolumab is Higher Than Expected.","authors":"Natalia Chamorro-Pareja, Alexander T Faje, Karen K Miller","doi":"10.1210/clinem/dgaf122","DOIUrl":"10.1210/clinem/dgaf122","url":null,"abstract":"<p><strong>Context: </strong>Adrenal insufficiency from hypophysitis is a complication of immune checkpoint inhibitor (ICI) therapy. However, the risk associated with relatlimab, a lymphocyte-activation gene 3 inhibitor, is unknown. Relatlimab was approved in 2022 in combination with nivolumab for the treatment of unresectable or metastatic melanoma.</p><p><strong>Objective: </strong>To determine the prevalence, identify risk factors, and characterize the clinical presentation of central adrenal insufficiency in patients receiving relatlimab-nivolumab compared to nivolumab alone.</p><p><strong>Methods: </strong>Retrospective analysis of Mass General Brigham healthcare system patients who received relatlimab-nivolumab from 2015 to 2023 matched by age, sex, and race to individuals receiving monotherapy with nivolumab, an ICI with a risk of hypophysitis of <1%.</p><p><strong>Results: </strong>Adrenal insufficiency was diagnosed in 10 patients (8%) after relatlimab-nivolumab administration and in 1 patient (<1%) after nivolumab monotherapy (P = .00056). Within the relatlimab-nivolumab group, median age and sex were comparable in patients who developed adrenal insufficiency compared to those who did not. The median number of doses received by subjects who developed adrenal insufficiency was 7 (4-10) compared to 3 (2-6) in those who did not (P = .03). The most common presenting symptoms were fatigue, anorexia, nausea, and vomiting. No patients were diagnosed with additional anterior pituitary hormone deficiencies or arginine vasopressin deficiency, though not all patients were evaluated for these diagnoses.</p><p><strong>Conclusion: </strong>This study is the first cohort analysis of hypophysitis in patients treated with relatlimab-nivolumab compared to nivolumab monotherapy. Combination treatment with relatlimab-nivolumab confers a significantly higher risk of developing adrenal insufficiency, likely secondary to hypophysitis, compared to nivolumab alone.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e3827-e3831"},"PeriodicalIF":5.1,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143505729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Menopause Has a Beneficial Influence on the Evolution of Prolactinomas. A Study of 99 Patients.","authors":"Stefan Matei Constantinescu, Caterina Maria Nava, Fanny Chasseloup, Orsalia Alexopoulou, Philippe Chanson, Dominique Maiter","doi":"10.1210/clinem/dgaf152","DOIUrl":"10.1210/clinem/dgaf152","url":null,"abstract":"<p><strong>Context: </strong>Menopause is thought to have beneficial effects in women with prolactinoma, potentially offering a higher chance for successful dopamine agonist (DA) withdrawal. However, strong evidence supporting this remains limited.</p><p><strong>Objective: </strong>To assess the impact of menopause on prolactinoma evolution and recurrence after DA withdrawal.</p><p><strong>Design: </strong>Retrospective study.</p><p><strong>Setting: </strong>Two tertiary academic hospitals.</p><p><strong>Patients: </strong>We retrospectively analyzed data from 99 women undergoing menopause (Mp, defined as 12 months of amenorrhea, low estradiol, and FSH > 25 U/L) while still on DA treatment for a prolactinoma (mean age at diagnosis: 37.9 ± 8.1 years). The tumors were microadenomas in 67 cases and macroadenomas in 32 (12 invasive).</p><p><strong>Results: </strong>In postmenopausal women continuing DA at stable doses, median prolactin levels decreased significantly from 18.0 µg/L before Mp to 9.8 µg/L 3 to 6 months after Mp (n = 71, P = .05) and to 7.9 µg/L after 24 months (n = 45, P < .001). Coronal surface also decreased significantly from 16.5 to 8.2 mm² at 24 months (n = 34, P < .01). DA treatment was successfully discontinued in 56 women, all meeting stringent criteria for discontinuation, with 41 (73%) remaining in remission over a median follow-up of 29 months. Recurrence occurred in 15 women (27%), mostly within the first year after DA withdrawal. Prolactin concentration measured 3 to 6 months after DA discontinuation was the only independent predictor of recurrence. Estrogen-progestin replacement therapy, given in 23 women, did not influence prolactinoma outcome.</p><p><strong>Conclusion: </strong>We confirm that menopause has a beneficial effect on the evolution of prolactinomas. When fulfilling stringent criteria for DA withdrawal, two-thirds of postmenopausal women can expect sustained remission, and recurrences are generally mild and asymptomatic.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e3701-e3708"},"PeriodicalIF":5.1,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship of Carbohydrate Intake Proportion to Cardiovascular Events in Japanese People With Type 2 Diabetes Mellitus.","authors":"Tomoya Mita, Yusuke Osonoi, Yuki Someya, Takeshi Osonoi, Miyoko Saito, Shiho Nakayama, Hidenori Ishida, Ryota Ishii, Masahiko Gosho, Hirotaka Watada","doi":"10.1210/clinem/dgaf179","DOIUrl":"10.1210/clinem/dgaf179","url":null,"abstract":"<p><strong>Background: </strong>It remains largely unknown whether a low-carbohydrate diet is associated with cardiovascular disease and all-cause mortality, and also if low-carbohydrate diets consisting of different nutrients could have different effects on these outcomes in people with type 2 diabetes.</p><p><strong>Objective: </strong>This prospective observational study investigated which lifestyle habits were associated with an increased risk of health outcomes.</p><p><strong>Methods: </strong>The study participants comprised 731 Japanese outpatients with type 2 diabetes and no evident cardiovascular disease history. Lifestyle habits, including diet, were assessed with questionnaires at baseline and at years 2 and/or 5, and their mean values were calculated using the average value of lifestyle factors from baseline to the date of onset of an event or the end of follow-up. A multivariable Cox proportional hazards model was used to determine the relationships between each lifestyle habit and the primary endpoint events, comprising cardiovascular events and all-cause mortality.</p><p><strong>Results: </strong>During the mean follow-up period of 7.5 ± 2.4 years, composite primary endpoint events occurred in 55 participants. Multivariate Cox models showed a significant positive association between the mean proportion of carbohydrate intake and the primary endpoint incidence (hazard ratio = 1.06; 95% CI, 1.02-1.10; P = .005); in addition, the mean total low-carbohydrate diet score, animal low-carbohydrate diet score, and mean proportion of saturated fatty acid intake showed significant inverse associations with the incidence of the primary endpoint.</p><p><strong>Conclusion: </strong>Our data demonstrated that a higher proportion of carbohydrate intake, particularly with reduced consumption of animal-derived fat/protein, was correlated with an increased risk of cardiovascular disease and all-cause mortality. These data underscore the need to consider dietary components in people with type 2 diabetes.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e3587-e3595"},"PeriodicalIF":5.1,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kisspeptin Administration Stimulates Reproductive Hormones but Does Not Affect Anxiety in Humans.","authors":"Edouard G Mills, Layla Thurston, Lisa Yang, Tia Hunjan, Maria Phylactou, Bijal Patel, Sophie A Clarke, Chioma Izzi-Engbeaya, Jovanna Tsoutsouki, Megan Young, Paul Bech, Natalie Ertl, Matthew B Wall, Ali Abbara, Alexander N Comninos, Waljit S Dhillo","doi":"10.1210/clinem/dgaf128","DOIUrl":"10.1210/clinem/dgaf128","url":null,"abstract":"<p><strong>Context: </strong>Kisspeptin is a critical endogenous activator of the reproductive system, with escalating clinical interest as a novel therapeutic for common reproductive and psychosexual disorders. However, conflicting animal data suggest that kisspeptin can have anxiolytic, neutral, or anxiogenic effects.</p><p><strong>Objective: </strong>Given the rapid development of kisspeptin-based therapeutics, it is important to comprehensively investigate the effects of kisspeptin administration on behavioral, biochemical, and physiological measures of anxiety in humans.</p><p><strong>Methods: </strong>Ninety-five participants (N = 63 male, N = 32 female) completed a double-blind, randomized, placebo-controlled, crossover protocol (mean age ± SEM 30.9 ± 0.9 y, body mass index 24.0 ± 0.4), attending both for a 75-minute intravenous kisspeptin-54 infusion (1 nmol/kg/h) and rate-matched placebo (in random order). Behavioral, biochemical, and physiological measures of anxiety were compared between kisspeptin and placebo visits, using a state-anxiety psychometric questionnaire before and at the end of the infusions, and blood sampling (for reproductive hormones and cortisol) and heart rate measurements at 15-minute intervals. Blood pressure assessment took place before and at the end of the infusions.</p><p><strong>Results: </strong>Kisspeptin administration robustly increased serum luteinizing hormone to similar levels previously described using this administration protocol, confirming that the dose was biologically active (P < .001). State anxiety was not significantly altered by kisspeptin, compared to placebo (P = .13). Moreover, kisspeptin had no significant effects on circulating cortisol (P = .73), systolic (P = .74) or diastolic blood pressure (P = .90), or heart rate (P = .52).</p><p><strong>Conclusion: </strong>This is the first study demonstrating that a biologically active dose of kisspeptin to men and women does not affect behavioral, biochemical, or physiological measures of anxiety. Given that animal studies have yielded contradictory results, this provides key clinical data and reassurance that kisspeptin does not induce anxiety in humans and so informs the current development of kisspeptin-based therapeutics for common reproductive and psychosexual disorders.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"3133-3141"},"PeriodicalIF":5.1,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12527446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Race-neutral Pediatric Reference Ranges for Bone Mineral Density Predict Prospective Fractures in Childhood.","authors":"Babette S Zemel, Karen K Winer, Andrea Kelly, David S Freedman, Jonathan A Mitchell, David R Weber, Shana E McCormack, Tara McWilliams, Joan M Lappe, Sharon E Oberfield, John A Shepherd, Struan F A Grant, Heidi J Kalkwarf","doi":"10.1210/clinem/dgaf183","DOIUrl":"10.1210/clinem/dgaf183","url":null,"abstract":"<p><strong>Introduction: </strong>Race-specific reference ranges for pediatric areal bone mineral density (BMD) are widely used, but the value of race-based clinical algorithms has been questioned. We developed race-neutral pediatric reference ranges for areal BMD and bone mineral apparent density (BMAD) and compared race-specific vs race-neutral Z-scores in their ability to predict prospective fractures.</p><p><strong>Material and methods: </strong>This secondary analysis of the Bone Mineral Density in Childhood Study used longitudinal BMD data of the spine, hip, forearm, and total body less head and BMAD from dual-energy x-ray absorptiometry (DXA) scans. Race/ethnicity, dietary calcium, physical activity, and prospective fractures were assessed by questionnaire. Race-neutral reference ranges and height-for-age Z-score adjustment equations were created using the lambda-sigma-mu method. Race-neutral and race-specific Z-scores were compared using linear mixed-effect modeling. Cox proportional hazard modeling was used to test whether race-neutral Z-scores associated with fracture.</p><p><strong>Results: </strong>Race-neutral BMD and BMAD Z-scores were 0.5 to 0.7 SD greater than race-specific Z-scores for Black children but only ∼0.1 SD lower for children from other race/ethnicity groups. Growth and lifestyle factors modified group differences. One SD increase in race-neutral Z-scores was associated with a 12% to 18% reduced risk of fracture.</p><p><strong>Conclusion: </strong>We present the first race-neutral pediatric reference ranges for BMD and BMAD that are weighted to be representative of the US population and demonstrate that these Z-scores associate with fracture risk. Adoption of these new reference ranges should be considered, with thoughtful implementation for patients previously monitored with race-specific reference ranges, especially among children who identify as Black.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"3034-3048"},"PeriodicalIF":5.1,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12527452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silver-Russell Syndrome in 2025: Is It Still a Distinct Diagnostic Entity?","authors":"Eloïse Giabicani, Amélie Perriere, Irène Netchine","doi":"10.1210/clinem/dgae902","DOIUrl":"10.1210/clinem/dgae902","url":null,"abstract":"","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e3905-e3906"},"PeriodicalIF":5.1,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142923816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipodystrophy Severity Score to Assess Disease Burden in Lipodystrophy.","authors":"Rebecca J Brown, Baris Akinci, Matheos Yosef, Helen Phillips, Shokoufeh Khalatbari, Ekaterina Sorkina, Ferruccio Santini, Corinne Vigouroux, Maiah Brush, Rasimcan Meral, Giovanni Ceccarini, Mujdat Zeybel, Flavia Prodam, Julia von Schnurbein, Gian P Sorice, Merve C Guler, Nivedita Patni, Seher Tanrikulu, Saif Alyaarubi, Basak S Ozgen, Maria C Foss-Freitas, Secil Ozisik, Benerice Segrestin, Busra Ozcan, Suleyman C Adiyaman, Gianluca Musolino, Hilal Sekizkardes, Carla Musso, Yael Lebenthal, Samim Ozen, Vinaya Simha, Ilgin Y Simsir, Anna Stears, Thomas Scherer, Alessandra Gambineri, Josivan G Lima, Robert Semple, Martin Wabitsch, David Araujo-Vilar, Robert A Hegele, Elif A Oral","doi":"10.1210/clinem/dgaf103","DOIUrl":"10.1210/clinem/dgaf103","url":null,"abstract":"<p><strong>Context: </strong>Lipodystrophy syndromes are rare disorders characterized by deficient adipose tissue, leading to insulin resistance, dyslipidemia, and organ system abnormalities.</p><p><strong>Objective: </strong>Our goal was to develop a lipodystrophy severity score (LDS) to holistically capture the diverse manifestations of lipodystrophy into a numerical score to aid in prediction of clinical outcomes and/or treatment impact.</p><p><strong>Design: </strong>An 8-domain LDS was developed by 8 disease experts in consultation with patient organizations. The LDS was rated for feasibility and content validity by 28 additional clinicians and 9 patient representatives. LDS was compared to the Clinical Global Impression (CGI) of severity for 20 putative patient profiles, each at 2 different time points, and by comparing change in LDS to global impression of change. For external validation, LDS was calculated in 2 cohorts of patients with lipodystrophy treated with metreleptin.</p><p><strong>Results: </strong>LDS domains include Diabetes/Insulin Resistance, Microvascular Complications of Diabetes, Lipids, Cardiovascular, Liver, Kidney, Reproductive, and Other. Each domain is assessed by 1 or more questions assessing both lifetime and recent complications of lipodystrophy. The LDS had high content validity and feasibility and high reliability by intraclass correlation coefficients (>0.95). Global and domain-specific LDS were strongly correlated with CGI, as were changes in scores across visits (R = 0.79-0.99, P < .001 for all). In generalized lipodystrophy, metreleptin significantly reduced LDS (from 46 to 26 at 12 months, P < .001). The reductions were smaller in partial lipodystrophy (from 65 to 61 at 12 months, P = .04).</p><p><strong>Conclusion: </strong>The LDS can reflect the severity of diverse manifestations of lipodystrophy and monitor changes following interventions.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"3243-3255"},"PeriodicalIF":5.1,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Does Adjuvant Mitotane Impact Cure Rates in Adrenocortical Carcinoma? Insights From the ICARO-GETTHI/SEEN Registry.","authors":"Alberto Carmona-Bayonas, Cristina Álvarez-Escolá, Inmaculada Ballester Navarro, Jorge Hernando Cubero, Miguel Ángel Mangas Cruz, Rogelio Garcia-Centeno, Clara Iglesias, Jesús García-Donas, María José Picón, Miguel Paja, Lorena González Batanero, Lourdes García, Teresa Alonso Gordoa, Carlos López, Felicia Hanzu, Javier Martínez-Trufero, Beatriz Febrero, Patricia Saiz-López, Concepción Blanco Carrera, Teresa Ramón Y Cajal, Brenda Veiguela, Oswaldo Gressani, Nuria Valdés, Paula Jimenez-Fonseca","doi":"10.1210/clinem/dgaf082","DOIUrl":"10.1210/clinem/dgaf082","url":null,"abstract":"<p><strong>Context: </strong>Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy with a high risk of postoperative recurrence. Although adjuvant mitotane is commonly used, its potential for achieving cure rather than simply postponing inevitable recurrence remains uncertain.</p><p><strong>Objective: </strong>This study investigates whether mitotane impacts ACC recurrence patterns by preventing or delaying recurrence.</p><p><strong>Methods: </strong>This retrospective analysis used data from the ICARO-GETTHI/SEEN registry, which includes 36 Spanish hospitals. Recurrence in nonmetastatic ACC patients after resection was analyzed using Cox models, flexible longitudinal models, and mixture cure models to evaluate the impact of mitotane.</p><p><strong>Results: </strong>Among 244 patients, 133 (52%) received adjuvant mitotane, with therapeutic levels monitored in 84%. Findings suggest a possible \"cure fraction\" with a 32.5% estimated 30-year cure rate (95% CI, 23.4%-45.0%). Cox regression indicated a 39% reduced recurrence risk (HR 0.61; 95% CI, 0.39-0.95) for mitotane-treated patients, with effects diminishing over 24 months. Mixture cure models suggest mitotane primarily delays rather than prevents recurrence. Effect modification analysis showed significant benefit in male patients (HR 0.33; 95% CI, 0.16-0.69), younger patients, tumors with higher Ki-67% (modeled as a continuous variable), and those with venous invasion (HR 0.47; 95% CI, 0.27-0.82), with potential synergy when combined with radiotherapy.</p><p><strong>Conclusion: </strong>This study underscores the intriguing possibility that adjuvant mitotane delays recurrence, yet questions remain as to its curative capacity. The early benefit suggests a cytostatic effect, but certain subgroups-especially males, younger individuals, and those with high-risk tumors-may experience a more durable outcome. Further research is needed to explore mitotane's curative potential in ACC management.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"3155-3167"},"PeriodicalIF":5.1,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platelet Function and Markers of Atherothrombotic Risk in Individuals With Parathyroid Disorders.","authors":"Anda Mihaela Naciu, Annunziata Nusca, Andrea Palermo, Francesco Piccirillo, Gaia Tabacco, Alessandra D'Amico, Alfonso Maria Di Tommaso, Giulia Sterpetti, Michele Mattia Viscusi, Federico Bernardini, Maurizio Forte, Luca D'Ambrosio, Giacomo Frati, Cristina Nocella, Nicola Napoli, Roberto Carnevale, Sebastiano Sciarretta, Francesco Grigioni","doi":"10.1210/clinem/dgaf138","DOIUrl":"10.1210/clinem/dgaf138","url":null,"abstract":"<p><strong>Context: </strong>Both primary hyperparathyroidism (PHPT) and chronic hypoparathyroidism (HypoPT) are associated with the onset and development of cardiovascular diseases (CVDs). However, the molecular mechanisms underlying the effects of parathyroid disorders on endothelial dysfunction and platelet aggregation, two main determinants of CVDs, are not completely understood.</p><p><strong>Objective: </strong>This work aimed to evaluate the effects of PHPT and HypoPT on oxidative stress and endothelial and platelet function.</p><p><strong>Methods: </strong>This monocentric cross-sectional study at an outpatient clinic included 40 individuals with HypoPT, 40 with PHPT, and 40 age- and sex-matched control participants. Main outcome measures included circulating levels of markers of oxidative stress, endothelial function, and platelet activation, calcium metabolism parameters, flow-mediated vasodilation (FMD), and carotid intimal-media thickness (IMT).</p><p><strong>Results: </strong>HypoPT and PHPT patients showed increased oxidative stress markers as compared to control participants (P < .001). Among patients with parathyroid disorders, those with PHPT demonstrated the highest reduction of nitric oxide (P < .001 vs HypoPT and controls) and FMD (P < .001 and P = .001) and a marked increase of IMT (P < .001 and P = .001). We also observed an increased platelet aggregation in patients with parathyroid disorders, with the highest values in PHPT patients (P < .001, PHPT vs controls; P = .006, HypoPT vs controls; P < .001, PHPT vs HypoPT), along with increased levels of soluble P selectin and thromboxane B2.</p><p><strong>Conclusion: </strong>PHPT and HypoPT patients have increased markers of atherothrombotic risk due to endothelial and platelet function alterations. Our results suggests that parathyroid hormone may influence platelet reactivity. Further research is needed to determine if personalized antiplatelet therapy is necessary in individuals with parathyroid disorders.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e3745-e3755"},"PeriodicalIF":5.1,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of Leydig Cell Dysfunction in Previous Illicit Androgen Users.","authors":"Yeliz Bulut, Niels Brandt-Jacobsen, Rasmus Madsen, Mario Thevis, Jan Frystyk, Jakob Albrethsen, Niels Jørgensen, Anders Juul, Caroline Kistorp, Jon Jarløv Rasmussen","doi":"10.1210/clinem/dgaf157","DOIUrl":"10.1210/clinem/dgaf157","url":null,"abstract":"<p><strong>Background and objectives: </strong>A few studies have explored the impairment of pituitary gonadotroph and Leydig cell function in men who recently ceased illicit androgen use, as assessed by stimulation tests. However, the capacity of the pituitary-testis axis in previous users who discontinued androgen use years ago remains unclear. This study evaluated the pituitary-testis-axis capacity in previous illicit androgen users and nonusers.</p><p><strong>Methods: </strong>We conducted a cross-sectional study of recreational strength training men with (n = 30) and without (n = 26) a history of illicit androgen use. Previous users were subdivided into 2 subgroups based on detectable (group 1, n = 17) and undetectable (group 2, n = 13) performance-enhancing drugs in the urine.We performed gonadotropin-releasing hormone and human chorionic gonadotropin (hCG) stimulation tests. Serum LH was measured with immunoassay, total testosterone, and insulin-like factor 3 with liquid chromatography-tandem mass spectrometry. Sexual function was assessed using the 15-question International Index of Erectile Function questionnaire.</p><p><strong>Results: </strong>Elapsed duration since androgen cessation, geometric mean (95% confidence interval), was 1.9 (1.2; 3.0) years in previous androgen users. The mean (SD) age of all participants was 33 (8) years.Testosterone secretion after hCG injection was lower in previous users than nonusers: group 1 difference, -6.4 (-11.3; -1.5) nmol/L, (P = .031); group 2 difference, -14.2 (-19.5; -8.8) nmol/L, (P < .001). LH secretion did not differ between the groups.Multivariate linear regressions using erectile function as a dependent variable revealed that higher testosterone secretion during the hCG test (P = .046) was independently associated with better erectile function, whereas baseline serum testosterone (P = .780) and estradiol (P = .405) were not.</p><p><strong>Conclusion: </strong>Previous illicit androgen users exhibited decreased Leydig cell capacity 2 years after androgen cessation, which potentially influences erectile function.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e3709-e3718"},"PeriodicalIF":5.1,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}