The Journal of clinical endocrinology and metabolism最新文献

{"title":"Stress-Associated Testosterone Suppression: Central Adaptation or Hypogonadism?","authors":"Karl E Friedl, Bradley C Nindl, Adam W Potter","doi":"10.1210/clinem/dgag181","DOIUrl":"https://doi.org/10.1210/clinem/dgag181","url":null,"abstract":"<p><p>Low circulating testosterone in physically stressed populations is frequently interpreted as evidence of hypogonadism or intrinsic gonadal dysfunction. However, convergent data from military field studies, endurance athletes, and competitive stress models demonstrate that testosterone suppression during sustained stress is commonly a centrally mediated, reversible adaptation rather than intrinsic testicular failure. Severe energy deficit, sleep disruption, and uncontrollable psychogenic stress suppress hypothalamic gonadotropin-releasing hormone and luteinizing hormone pulsatility, reduce testicular androgen production, and frequently increase sex hormone-binding globulin (SHBG), thereby disproportionately lowering free testosterone. Human chorionic gonadotropin stimulation studies confirm preserved Leydig cell responsiveness under these conditions, supporting hypothalamic-pituitary inhibition as the dominant mechanism. In contrast, high mechanical loading in resistance-trained men does not suppress basal testosterone when energy availability is maintained, underscoring energetic sufficiency, not exercise modality, as the principal determinant of androgen tone. Acute competitive stress produces rapid, appraisal-dependent modulation of testosterone independent of SHBG, further demonstrating central regulation. Across contexts, androgen suppression tracks energetic and psychological constraint and is reversible with restoration of energy balance and recovery. Recognition of this adaptive endocrine phenotype is essential to distinguish functional central suppression from pathological hypogonadism and to guide appropriate clinical evaluation.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147795829","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":"Endocrine Characteristics in Bardet Biedl Syndrome from a Large Single-Centre Paediatric Multidisciplinary Clinic.","authors":"Rachel S Varughese, Divya Pujari, Elizabeth Hatton, Theodora Dyakova, Kathryn Sparks, Sarah Flack, Antonia Dastamani, Harshini Katugampola, Sinead McGlacken-Byrne, Catherine Peters, Dillon Schoeneberg, Jennifer Whitehead, Elizabeth Forsythe, Philip L Beales, Alexander D Chesover","doi":"10.1210/clinem/dgag184","DOIUrl":"https://doi.org/10.1210/clinem/dgag184","url":null,"abstract":"<p><strong>Objective: </strong>Bardet-Biedl syndrome (BBS) is a rare genetic ciliopathy characterised by obesity, rod-cone dystrophy, polydactyly, hypogonadism, cognitive impairment and renal abnormalities. Additional endocrine associations include short stature and hypothyroidism. The endocrine characteristics in children are not well described.</p><p><strong>Methods: </strong>A retrospective analysis of prospectively collected data in paediatric patients with genetically confirmed BBS from a single multidisciplinary BBS service. Data related to endocrine function were extracted from the electronic patient record. Height was reported for patients ≥4 years old and ≥15 years old. Short stature was defined as a height Z-score (standard deviation score, SDS) <-2 or height >1.6 SDS below the mid-parental height.</p><p><strong>Results: </strong>135 patients were included: 69 (51%) were female, ranging from 1.2-19.4 years old. At ≥15 years, 21.1% (12/57) had short stature and 77.6% (45/58) had obesity. On average, BMI worsened over time. Triglycerides were raised in 55.5% (66/119). No patients demonstrated biochemical or clinical evidence of persistent primary or secondary hypogonadism, and none required pubertal induction or sex steroid replacement therapy. Primary hypothyroidism and subclinical hypothyroidism were identified in 1.7% (2/121) and 0.8% (1/121), respectively. Type 1 diabetes, Type 2 diabetes and impaired glucose tolerance were identified in 1.5% (2/135), 2.2% (3/135) and 1.5% (2/135), respectively.</p><p><strong>Conclusions: </strong>This is the largest analysis of endocrine characteristics in paediatric patients with BBS. Short stature and obesity are characteristic of paediatric BBS. However, hypogonadism, hypothyroidism, and insulin resistance are less prevalent compared with adult BBS populations. Longitudinal studies spanning paediatric and adult populations may further characterise the natural history of these endocrine conditions associated with BBS.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147795898","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":"Deterioration Of Blood Lipids During Early Postoperative Remission Of Cushing's Syndrome: A Longitudinal Cohort Study.","authors":"Moritz Schrenk, Michael Haenelt, Matthias Oettle, Markus Kroiss, Stephanie Zopp, Leah T Braun, German Rubinstein, Katrin Ritzel, Isabel Stüfchen, Ulrich Stifel, Katharina Schilbach, Martin Bidlingmaier, Daniel Teupser, Felix Beuschlein, Martin Reincke, Frederick Vogel, Elisabeth Nowak","doi":"10.1210/clinem/dgag178","DOIUrl":"https://doi.org/10.1210/clinem/dgag178","url":null,"abstract":"<p><strong>Context: </strong>Cushing´s syndrome (CS) is associated with an unfavorable lipid profile. However, data on lipid alterations during early postoperative remission, a particularly cardiovascular vulnerable period, are lacking.</p><p><strong>Objective: </strong>Evaluation of lipid profiles during active CS and the early postoperative period.</p><p><strong>Patients and methods: </strong>In this single-center cohort study at LMU Hospital Munich, we analyzed lipid profiles (Total cholesterol, LDL, HDL, ApoA1, ApoB, Lipoprotein (a), Triglycerides and Non-esterified fatty acids) and metabolic markers in 26 patients with endogenous CS before surgery and 1, 3, 6, 12 and 24 months (n=23) after curative surgery, and compared them with 26 age-, BMI-, and sex-matched controls without hypercortisolism at baseline.</p><p><strong>Results: </strong>Paradoxically most lipid parameters postoperatively worsened. One month postoperatively, HDL (1mo postoperative 38 mg/dL [35-46] vs. active CS 49.5 mg/dL [45-61.3], p<0.0001) and ApoA1 concentrations (1mo postoperative 160 mg/dL [147-168] vs. active CS 193 mg/dL [169-211], p<0.0001) were significantly lower compared to preoperative levels. Similarly one month following surgery triglycerides concentrations (1mo postoperative 185 mg/dL [154-218] vs. active CS 129 mg/dL [89.3-186] preoperatively, p<0.0001) were higher. These changes remained evident until 6 months post-surgery. The triglyceride-glucose index increased during early remission and showed a positive correlation with inflammatory markers CRP and IL-6. Non-esterified fatty acids displayed three distinct postoperative trajectories depending on BMI at baseline.</p><p><strong>Conclusion: </strong>During the early remission phase following curative surgery, we observed a further deterioration in lipid parameters. This can affect cardiovascular health and provides the basis for targeted therapy.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147795775","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":"Pituitary Adenoma Imaging as a Determinant of Acromegaly Diagnosis and Outcomes.","authors":"Linus Haberbosch, James MacFarlane, Daniel Gillett, Sophie Howarth, Jonathan Jones, Heok Cheow, Vanessa Hubertus, Güliz Acker, Leontine Bakker, Marco Verstegen, Lenka Pereira Arias-Bouda, Nienke Biermasz, Michael Buchfelder, Christian J Strasburger, Mark Gurnell","doi":"10.1210/clinem/dgag179","DOIUrl":"https://doi.org/10.1210/clinem/dgag179","url":null,"abstract":"<p><p>In the majority (> 95%) of patients with acromegaly, the underlying cause is a somatotroph adenoma. Pituitary-targeted surgery and radiotherapy can achieve long-term disease control but carry a significant adverse risk to the remaining normal gland, especially if undertaken outside a Pituitary Tumor Center of Excellence or when repeat surgery is performed. Maximizing benefits and minimizing risks of pituitary surgery and radiotherapy is critically dependent on high-quality imaging that allows accurate localization of site(s) of either de novo, residual or recurrent disease. Macroadenomas continue to predominate among somatotroph tumors (70%), but more widespread use of intracranial imaging is leading to the earlier detection of smaller adenomas, which pose new challenges for imaging diagnostics. Despite several comprehensive guidelines on the management of acromegaly, there is little consensus regarding optimal imaging and current scanning protocols remain heterogeneous. This serves as a barrier to optimal patient management and constrains comparison between centers, with inevitable consequences for research within the field. Here, based on a comprehensive review of previous studies and focusing on recent advances in magnetic resonance and molecular (functional) imaging techniques, we propose a standardized, tiered approach to pituitary imaging in patients with acromegaly, guided by individual patient features and tailored to the anticipated therapeutic approach. An online tool, which can be adapted to the clinical context, is provided as an aid to decision-making.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147795878","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 Kaminska et al: \"Overnight Wakefulness Impairs Next-Day Postprandial Glucose in Young Women Independent of Sex Hormones\".","authors":"Halla Kaminska, Michal Pruc, Wojciech Wieczorek, Lukasz Szarpak","doi":"10.1210/clinem/dgag106","DOIUrl":"https://doi.org/10.1210/clinem/dgag106","url":null,"abstract":"","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147795892","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":"Adenoma Receptors and Histologic Characteristics Determining Management Outcomes.","authors":"Luiz Eduardo Wildemberg, Mônica R Gadelha","doi":"10.1210/clinem/dgag180","DOIUrl":"https://doi.org/10.1210/clinem/dgag180","url":null,"abstract":"<p><p>Patient responses to medical therapy for acromegaly are variable. Adenoma features, including histologic characteristics and receptor density, are closely associated with distinct clinical behavior and therapeutic outcomes. Densely granulated pure somatotropinomas respond more favorably to somatostatin receptor subtype 2 (SST2)-selective ligands (octreotide and lanreotide) compared with sparsely granulated adenomas. In contrast, sparsely granulated adenomas may respond more favorably to pasireotide, which has higher affinity for somatostatin receptor subtype 5 (SST5). Expression levels of SST2 receptors are also associated with responsiveness to octreotide and lanreotide, whereas response to pasireotide is linked to higher SST5 expression. Recent prospective studies have highlighted that treatment strategies guided by biomarkers determining therapeutic response are more effective than standard, non-biomarker-based approaches. Current evidence supports the incorporation of biomarkers into decision-making for medical management of acromegaly, while these approaches are being further validated.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147795751","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 Claahsen and Kamrath: \"the importance of disease-Specific growth charts for children with congenital adrenal hyperplasia\".","authors":"Hedi L Claahsen-van der Grinten, Clemens Kamrath","doi":"10.1210/clinem/dgag159","DOIUrl":"https://doi.org/10.1210/clinem/dgag159","url":null,"abstract":"","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147795821","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":"The effectiveness of hormonal treatment to improve reproductive outcomes in normo-gonadotropic men with abnormal semen parameters: Results of two linked systematic reviews.","authors":"Kristin Konnyu, Mari Imamura, Jemma Hudson, James Swingler, Paul Manson, Siladitya Bhattacharya, Channa N Jayasena, Miriam Brazzelli","doi":"10.1210/clinem/dgag185","DOIUrl":"https://doi.org/10.1210/clinem/dgag185","url":null,"abstract":"<p><strong>Context: </strong>Growing numbers of international guidelines recommend hormonal treatment for normogonadotropic men with abnormal semen parameters, despite uncertain effects on fertility outcomes.</p><p><strong>Objective: </strong>Evaluate the efficacy of hormonal treatment, compared with placebo or no treatment, in normogonadotropic men with abnormal semen parameters.</p><p><strong>Data sources: </strong>We searched MEDLINE, Embase, the Cochrane Database of Systematic Reviews, and CENTRAL to February 2025.</p><p><strong>Study selection: </strong>Two linked reviews were conducted simultaneously. Review 1 included randomised and non-randomised controlled studies evaluating hormonal treatments in normogonadotropic men with abnormal semen parameters. Review 2 included the same treatments in men undergoing assisted reproduction. All citations were double-screened.</p><p><strong>Data extractio: </strong>n Primary outcomes were changes in semen quality (in Review 1) and pregnancy (in Review 2). Risk of bias of the included studies was assessed using the Cochrane tool and ROBUST-RCT. Random-effects meta-analyses were performed.</p><p><strong>Data synthesis: </strong>Nine studies (735 men) were included. Follicle-stimulating hormone (FSH) showed modest improvements in sperm count (Mean Difference [MD] 11.0, 95% confidence interval [CI] 7.2, 14.8), concentration (MD 5.6, 95% CI 1.9, 9.3) and motility (MD 3.4, 95% CI 0.7, 6.0) but not morphology (MD 4.7, 95% CI -0.8, 10.3). Studies of combined human chorionic and menopausal gonadotropins, as well as tamoxifen, showed no benefit. Two small studies reported non-significant increases in pregnancy with FSH. No eligible studies evaluated aromatase inhibitors or clomiphene.</p><p><strong>Conclusions: </strong>We cautiously report potential for selective use of FSH in normogonadotropic men. However, the expected benefits are modest and short-term, with uncertain translation to pregnancy or live birth.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147795827","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":"Digenic HNF1A and ABCC8 Variants Provide Mechanistic Insight into Early-Onset Diabetes.","authors":"Makie Honda, Ryo Honda, Teiko Komori Nomura, Yuichi Nishikado, Yoshihiro Takahashi, Kazuyoshi Hosomichi, Shin Tsunekawa, Daisuke Yabe, Yukio Horikawa","doi":"10.1210/clinem/dgag183","DOIUrl":"https://doi.org/10.1210/clinem/dgag183","url":null,"abstract":"<p><strong>Context: </strong>Oligogenic inheritance in maturity-onset diabetes of the young (MODY) remains poorly characterized, and the contribution of multiple candidate variants to disease pathogenesis is incompletely understood.</p><p><strong>Objective: </strong>To investigate the pathogenicity and mechanistic contribution of multiple MODY gene variants identified in a MODY-like family and determine their role in early-onset diabetes.</p><p><strong>Methods: </strong>Comprehensive genetic analysis of known MODY genes was performed in a MODY-like family. Functional effects of HNF1A and HNF1B variants were assessed using luciferase reporter assays in HEK293T cells. Functional characterization of ABCC8 variants included Kir6.2-dependent thallium (Tl+) flux assays, sulfonylurea responsiveness, and channel stability.</p><p><strong>Results: </strong>Four variants in three MODY genes were identified in the proband: novel p.Ser551Lysfs*2, HNF1B p.Glu102Ala, and ABCC8 p.Arg298Cys and p.Arg521Gln. Functional analysis showed that HNF1A p.Ser551Lysfs*2 retained approximately 5% of wild-type transactivation activity, consistent with loss-of-function, whereas HNF1B p.Glu102Ala and ABCC8 p.Arg521Gln exhibited wild-type-like function. In contrast, ABCC8 p.Arg298Cys reduced channel activity to 77% of wild-type levels while preserving sulfonylurea responsiveness. Segregation analysis identified HNF1A p.Ser551Lysfs*2 and ABCC8 p.Arg298Cys in affected parents. The proband, who inherited both pathogenic variants, developed diabetes earlier than either parent and was exposed to maternal hyperglycemia in utero, which may also have contributed to this early onset.</p><p><strong>Conclusions: </strong>Functional characterization distinguishes pathogenic from variants of unknown significance and supports digenic inheritance of HNF1A and ABCC8. Their additive effects, together with intrauterine hyperglycemia, likely accelerated disease onset. This study provides mechanistic evidence for oligogenic contributions to MODY and expands the genetic architecture of early-onset diabetes.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147795883","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":"Implementation of a Spanish-language, direct-to-patient primary aldosteronism testing program.","authors":"Arnaldo Ferrebus, Laura C Tsai, Eva E Abel, Kristen Foote, Andrew J Newman, Stéfanie Parisien-La Salle, Cheng-Hsuan Tsai, Anand Vaidya, Jenifer M Brown","doi":"10.1210/clinem/dgaf663","DOIUrl":"10.1210/clinem/dgaf663","url":null,"abstract":"<p><strong>Context: </strong>Primary aldosteronism (PA) is a common, targetable cause of hypertension and cardiovascular risk, but <2% of eligible patients are tested, and Hispanic/Latino patients are underrepresented in PA research and care.</p><p><strong>Objective: </strong>We expanded a nationwide, direct-to-patient PA testing program to reach Spanish-speaking adults.</p><p><strong>Methods: </strong>Spanish-speaking adults with PA testing indications were recruited from Boston, New York, Miami, Houston, and Los Angeles/San Diego. Participants underwent virtual medical history review in Spanish and local phlebotomy for PA testing, with laboratory interpretations communicated to patients and clinicians. Participants were followed up at 6 months. The primary outcome was the frequency of a positive PA test. Secondary outcomes included clinical PA testing, initiation of aldosterone-targeted therapies, and quality of life.</p><p><strong>Results: </strong>The study population (N = 155) spoke fluent Spanish, with 77.4% reporting limited English proficiency. Of the participants, 30.3% tested positive for PA. Leading PA testing indications were family history of premature hypertension or stroke and sleep apnea. Among participants who tested positive and provided follow-up (n = 29), 10.3% underwent additional testing for PA, and 10.3% started a mineralocorticoid receptor antagonist. Participants cited access to care and clinician dismissal of results as barriers to clinical action; however, study participation was positively rated to enhance health awareness and interest in research participation.</p><p><strong>Conclusion: </strong>This Spanish-language, direct-to-patient PA testing program effectively reached patients for testing, identified possible PA in over 30%, and influenced downstream care. Language-concordant PA testing initiatives can help to address the high prevalence of hypertension and PA in the US Hispanic/Latino population.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":"e1263-e1272"},"PeriodicalIF":5.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13099184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145728307","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}