European Journal of Endocrinology最新文献

{"title":"Soluble alpha klotho-impact of biological variables and reference intervals for adults.","authors":"Júnia Ribeiro de Oliveira Longo Schweizer, Katharina Schilbach, Michael Haenelt, Anica Gagliardo, Annette Peters, Barbara Thorand, Sylvère Störmann, Jochen Schopohl, Martin Reincke, Michael Lauseker, Martin Bidlingmaier","doi":"10.1093/ejendo/lvaf093","DOIUrl":"10.1093/ejendo/lvaf093","url":null,"abstract":"<p><strong>Objective: </strong>Concentrations of soluble alpha klotho (sαKL) are higher in active acromegaly compared with healthy controls. However, reference intervals based on large population-based samples are lacking, and the impact of many biological variables is unclear.</p><p><strong>Design: </strong>Cross-sectional study.</p><p><strong>Methods: </strong>We measured sαKL concentrations in samples from an adult population (20-89 years, 435 males, 455 females). Associations with sex, age, body mass index, waist-hip-ratio, estimated glomerular filtration rate (eGFR), IGF-I and IGFBP 3, glucose-, lipid-, calcium- and liver-metabolism, fasting, and estrogen status were analyzed. Reference intervals were calculated using LMS quantile regression with a Box-Cox transformation to normality. We also analyzed sαKL in patients with non-functioning pituitary adenoma (NFPA, n = 18) and prolactinoma (n = 65).</p><p><strong>Results: </strong>Across all ages, sαKL concentrations (pg/mL, median [interquartile ranges]) were slightly, but significantly higher in females compared with males (678 (537-859) vs. 651 (537-812), P = .01), suggesting an impact of estrogens. SαKL exhibited a weak negative correlation with age, and positive correlations with eGFR and IGF-I (P < .001 for both). Correlations to other biological factors including glucose, liver and calcium metabolism and duration of fasting were negligible (P > .05 for all). Compared with sαKL, IGF-I more often was correlated significantly to other biological variables. SαKL was not different in patients with NFPA, but slightly higher in patients with prolactinoma (P < .05).</p><p><strong>Conclusion: </strong>Our findings suggest sαKL is a stable GH-sensitive biomarker that may be less impacted by biological variables compared with IGF-I and IGFBP 3. Our reference intervals will facilitate the potential use of sαKL in GH-related diseases.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"631-640"},"PeriodicalIF":5.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thyroid axis adaptations to moderate short-term energy restriction in healthy, young women.","authors":"Skand Shekhar, Joselyne Tessa Tonleu, Chinelo C Okigbo, Helen Leka, Anne E Kim, Bona P Purse, Katie R Hirsch, Brian R Stolze, John A McGrath, Abbie E Smith-Ryan, Steven J Soldin, Janet E Hall","doi":"10.1093/ejendo/lvaf083","DOIUrl":"10.1093/ejendo/lvaf083","url":null,"abstract":"<p><strong>Objective: </strong>Short-term dieting has gained popularity in women. We studied thyroid hormone change after short-term, moderate energy restriction.</p><p><strong>Methods: </strong>Nineteen, healthy women aged 23.36 ± 2.08 yr (mean ± SD) without obesity and thyroidal disease underwent a neutral (NEA, ±0%) and a deficient (DEA, -55%) diet for 5 days each in the early follicular phases of successive menstrual cycles. Blood was sampled every 10 min between 8 AM and 4 PM and analyzed for TSH, GH, and cortisol every 30 min, total T3 (TT3), reverse T3 (rT3), and total T4 (TT4) hourly and free T3 (fT3), free T4 (fT4), and TBG at the beginning and end of the studies. Liquid chromatography-tandem mass spectrometry (LCMS) assessed all thyroid hormones except TSH and TBG. Data shown as mean difference or least squared (ls) mean (±SEM).</p><p><strong>Results: </strong>There was a small decrease in body mass index and body weight after DEA (0.4 ± 0.08 kg/m2; P < .001 and 1.1 ± 0.21 kg; P < .001, respectively), with unchanged fat mass. Compared to NEA, TT3 (ls mean ± SEM; 95.55 ± 2.89 ng/dL vs. 89.15 ± 2.89; P < .0001), and TSH (1.03 ± 0.07 vs. 0.92 ± 0.07 μIU/mL; P < .0001) declined while TT4 (6.06 ± 0.25 vs. 6.26 ± 0.25 μg/dL; P = .005), fT4 (1.71 ± 0.07 vs. 1.83 ± 0.07 ng/dL; P = .0052) and rT3 (9.02 ± 0.56 vs. 12.04 ± 0.56 ng/dL; P < .0001) increased after DEA with no change in TBG, GH and cortisol.</p><p><strong>Conclusion: </strong>Adaptive central and peripheral changes in thyroid hormones occur after short-term, moderate dieting in young women without obesity.</p><p><strong>Clinicaltrials.gov: </strong>NCT02858336.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"192 5","pages":"568-576"},"PeriodicalIF":5.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic variation underlies the heterogeneous risk of metabolic dysfunction-associated steatotic liver disease for subsequent chronic diseases.","authors":"Jialong Wu, Gonghua Wu, Jiawei Li, Bo Yi, Qingyi Jia, Ke Ju, Qingyang Shi, Zixuan Wang, Xiong Xiao, Bing Guo, Huan Xu, Xing Zhao","doi":"10.1093/ejendo/lvaf103","DOIUrl":"10.1093/ejendo/lvaf103","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a heterogeneous condition. Whether and how the plasma proteome underlies the heterogeneous associations between MASLD and subsequent health outcomes remain unclear.</p><p><strong>Methods: </strong>This study included 42 508 participants from the UK Biobank. Steatosis was defined by the fatty liver index. Individuals' MASLD-related proteomic signature was derived from 2911 plasma proteins. Cox models were used to assess the associations of the proteomic signature with 8 chronic diseases: liver fibrosis, cardiovascular disease (CVD), chronic kidney disease (CKD), chronic respiratory disease (CRD), dementia, depression, anxiety, and cancers. Adjusted survival curves were fitted to compare the cumulative incidence rate of diseases across quantiles of the proteomic signature; we further adjusted for the steatosis degree and cardiometabolic factors to test whether the association was independent of them. Mediation analyses were performed to identify mediating proteins.</p><p><strong>Results: </strong>The proteomic signature was significantly associated with liver fibrosis, CVD, CKD, CRD, and depression in the MASLD population, with adjusted hazard ratios ranging from 1.30 to 4.94. Survival curves showed that individuals with the highest proteomic signature had the highest risk for these 5 diseases. These risk differences by signature persisted after adjustment for steatosis degree and cardiometabolic factors, except for depression. Proteins including ADM, ASGR1, and FABP4 were identified as common mediators of the association between MASLD and multiple diseases. Mediators of liver fibrosis showed specificity, with CDHR2 being the key protein.</p><p><strong>Conclusions: </strong>Metabolic dysfunction-associated steatotic liver disease patients with the same steatosis severity but different proteomic responses may have different risks for future outcomes. Several key proteins may contribute to the progression of MASLD-related diseases.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"691-703"},"PeriodicalIF":5.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of hydrocortisone vs prednisone therapy on postsurgical recovery in patients with endogenous hypercortisolism: a prospective cohort study.","authors":"Rashi Sandooja, Jasmine Saini, Elio Ferreira Taveras, Raul Gregg-Garcia, Catherine D Zhang, Vanessa Fell, Anina Peersen, Sara J Achenbach, Elizabeth J Atkinson, Jamie J Van Gompel, William F Young, Irina Bancos","doi":"10.1093/ejendo/lvaf092","DOIUrl":"10.1093/ejendo/lvaf092","url":null,"abstract":"<p><strong>Objective: </strong>Glucocorticoid withdrawal syndrome (GWS) may develop in patients following successful surgery for endogenous hypercortisolism. Effective strategies to minimize GWS and improve quality of life (QoL) are currently lacking. We aimed to determine the impact of hydrocortisone vs prednisone therapy on GWS and QoL during the first 12 weeks postsurgery.</p><p><strong>Methods: </strong>Single-center prospective cohort study (2019-2024) of adults with endogenous hypercortisolism who developed postoperative adrenal insufficiency and treated with either prednisone or hydrocortisone. Quality of life was assessed with Short Form-36 (SF-36) and Cushing QoL questionnaires at baseline and at 12 weeks postsurgery. GWS was assessed using weekly AddiQoL questionnaires for the first 12 weeks postsurgery.</p><p><strong>Results: </strong>Of 165 patients, 101 (61%) were treated with hydrocortisone and 64 (39%) with prednisone. At baseline, no group differences were found in the hypercortisolism subtype, comorbidities, or QoL assessments. At follow-up, no group differences in final total daily hydrocortisone equivalent dose were seen.When adjusting for the baseline QoL assessment, patients treated with prednisone demonstrated a higher degree of improvement in their QoL, particularly in the SF-36 mental component score (estimate 0.33, 95% CI, 0.04-0.63), SF-36 role-emotional limitation (estimate 0.52, 95% CI, 0.2-0.84), and SF-36 body pain (estimate 0.31, 95% CI, 0.07-0.56) subcomponents. In the multivariable analysis of age, sex, body mass index, glucocorticoid type, baseline clinical severity score, and baseline QoL assessment, prednisone therapy was an independent predictor of better SF-36 mental component at 12 weeks postsurgery.</p><p><strong>Conclusions: </strong>Prednisone therapy was associated with better mental health QoL than hydrocortisone at 12 weeks postsurgery in patients with hypercortisolism.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"621-630"},"PeriodicalIF":5.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating immune cell profile in patients with acromegaly: results from the PROMISE, a prospective clinical trial.","authors":"Tiziana Feola, Dario De Alcubierre, Giulia Puliani, Alessia Cozzolino, Francesca Sciarra, Ludovica Vincenzi, Valeria Hasenmajer, Valentina Sada, Marialuisa Appetecchia, Elisa Giannetta, Emilia Sbardella, Marie-Lise Jaffrain-Rea, Mary Anna Venneri, Andrea M Isidori","doi":"10.1093/ejendo/lvaf085","DOIUrl":"10.1093/ejendo/lvaf085","url":null,"abstract":"<p><strong>Objective: </strong>Although GH and IGF-1 have long been proposed to play a role in immune-modulation, the circulating immune cell phenotype in acromegaly (ACRO) is poorly understood.</p><p><strong>Design: </strong>This observational, prospective, single-site clinical trial (NCT05069324) analyzed peripheral blood mononuclear cell (PBMC) subpopulations in ACRO, investigating the role of disease control, pharmacological treatments, and metabolic profile.</p><p><strong>Methods: </strong>Sixty consecutive patients with ACRO (34 males, mean age 54.7 ± 15) attending an outpatient visit between July 2020 and December 2024 were enrolled. Patients were compared with two populations: 40 healthy controls (CTRL) and 40 patients with type 2 diabetes (T2DM), with no significant differences in age or sex. An 8-week follow-up evaluation was performed and compared among patients according to the introduction or changes in their pharmacological treatment.</p><p><strong>Results: </strong>Compared with CTRL, ACRO patients had lower total monocytes with a decreased percentage of classical and an increased proportion of non-classical subsets. There were fewer NK cells, with higher CD56dim and lower CD56bright subpopulations, and similar T and B lymphocytes. Compared with T2DM, ACRO showed lower total monocytes, with higher classical and lower non-classical subsets, as well as lower NK cells and B lymphocytes. In the short-term, treatment appeared unable to restore immune cell profile but partially affected the distributions of innate immune cells subpopulations.</p><p><strong>Conclusions: </strong>This is the first evidence of a distinct immunological pattern in ACRO that is independent of glucose metabolism. The immune signature may contribute to the persistence of cardio-metabolic and oncological risk observed in ACRO, even when the disease is adequately controlled by medical treatment.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"192 5","pages":"577-589"},"PeriodicalIF":5.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of 24-week concurrent training on bone parameters and plasma levels of osteoglycin and sclerostin in young, sedentary adults: secondary analyses from the ACTIBATE randomized controlled trial.","authors":"Juan J Martin-Olmedo, Lucas Jurado-Fasoli, Francisco J Osuna-Prieto, Cristina García-Fontana, Beatriz García-Fontana, Luis Gracia-Marco, Manuel Muñoz-Torres, Jonatan R Ruiz","doi":"10.1093/ejendo/lvaf087","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf087","url":null,"abstract":"<p><strong>Objective: </strong>To examine the effects of 24-week moderate (MOD-EX) and vigorous-intensity concurrent training (VIG-EX) on bone parameters and plasma levels of osteoglycin and sclerostin and their interplay with body composition and cardiometabolic risk factors in young, sedentary men and women.</p><p><strong>Design: </strong>Secondary study from the ACTIBATE randomized controlled trial (ClinicalTrials.gov ID: NCT02365129).</p><p><strong>Methods: </strong>This study was performed at the Sport and Health University Research Institute and the Virgen de las Nieves University Hospital of the University of Granada. Bone parameters were measured by dual-energy X-ray absorptiometry, and osteoglycin and sclerostin levels, by enzyme-linked immunosorbent assay.</p><p><strong>Results: </strong>145 young sedentary adults were assigned to a control (CON, n = 54), a MOD-EX (n = 48), or a VIG-EX (n = 43). 106 participants were included in the per-protocol analyses (CON, n = 42; MOD-EX, n = 33; and VIG-EX, n = 31). After 24 weeks of concurrent training, we observed no differences in changes in bone parameters (all P time × group ≥ .300), osteoglycin (P time × group = .250), and sclerostin levels (P time × group = .489). Moreover, we found no correlations between osteoglycin and sclerostin levels with body composition (all P ≥ .639) and cardiometabolic risk factors (all P ≥ .119).</p><p><strong>Conclusion: </strong>24 weeks of concurrent training did not alter bone parameters, and plasma levels of osteoglycin and sclerostin in young, sedentary adults. Moreover, osteoglycin and sclerostin are not related with bone parameters and cardiometabolic risk factors in this population. These findings suggest that longer concurrent training interventions may be needed to enhance bone parameters in young, sedentary adults.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"192 5","pages":"558-567"},"PeriodicalIF":5.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conservatively managed non-functioning pituitary macroadenomas-cohort study from the UK Non-functioning Pituitary Adenoma Consortium.","authors":"Athanasios Fountas, Kirstie Lithgow, Paul Benjamin Loughrey, Efstathios Bonanos, Shah Khalid Shinwari, Kirsten Mitchell, Akash Mavilakandy, Masato Ahsan, Mike Matheou, Kristina Isand, Ross Hamblin, David S McLaren, Hafiz Zubair Ullah, Lydia Grixti, James MacFarlane, Anuradha Jayasuriya, Sumbal Bhatti, Wunna Wunna, Syed Shah, Ziad Hussein, Susan Mathew, Katarina Klaucane, John Ayuk, Andy Toogood, Georgios Tsermoulas, Shahzada Ahmed, Alessandro Paluzzi, Ruchika Batra, Joannis Vamvakopoulos, Amutha Krishnan, Claire Higham, Prakash Abraham, Stephanie E Baldeweg, Tejpal Purewal, Janki Panicker, Niamh Martin, William M Drake, Rupa Ahluwalia, John Newell-Price, Mark Gurnell, Yaasir Mamoojee, Antonia Brooke, Andrew Lansdown, Robert D Murray, Karin Bradley, Aparna Pal, Narendra Reddy, Miles J Levy, Ellen Marie Freel, Biju Jose, Steven J Hunter, Niki Karavitaki","doi":"10.1093/ejendo/lvaf091","DOIUrl":"10.1093/ejendo/lvaf091","url":null,"abstract":"<p><strong>Objective: </strong>Surveillance is often adopted for asymptomatic non-functioning pituitary macroadenomas (macroNFPAs). Due to low-quality evidence, uncertainty remains on optimal frequency of imaging/biochemical monitoring and indications for surgery. We assessed the natural history and outcomes of patients with macroNFPA who had monitoring as initial management choice from the UK NFPA Consortium.</p><p><strong>Design: </strong>This was a multicentre, retrospective, cohort study involving 21 UK endocrine departments.</p><p><strong>Methods: </strong>Clinical, imaging, and hormonal data of 949 patients followed up between January, 1, 2005 and March, 1, 2022 were analysed.</p><p><strong>Results: </strong>Incidence rate for tumour enlargement was 9.8 per 100 patient-years (95% CI, 8.8-10.8), with cumulative probabilities 1.6%, 8.1%, 18.4%, 29.2%, and 43.6% at 6-month, 1-year, 2-year, 3-year, and 5-year follow-up, respectively; rates were higher in tumours abutting/displacing optic chiasm than those not in contact with it. Amongst macroNFPAs not in contact with optic chiasm showing enlargement within 6 months, none impacted visual fields. In tumours with enlargement and continued monitoring (median 2.6 years), further growth occurred in 60.5% (33.8% probability at 2 years), stability in 35.5%, and shrinkage in 4.0%. Rates of new pituitary hormone deficits were 4.0%-4.9%, mainly driven by tumour enlargement. After transsphenoidal surgery, rates of hypopituitarism reversal were 12%-17% and those of additional anterior pituitary hormone deficits were 12%-15% (permanent vasopressin deficiency 3.5%).</p><p><strong>Conclusions: </strong>Our data provide evidence for monitoring protocols. MacroNFPAs not in contact with optic chiasm require less frequent imaging, and first follow-up scan can be delayed to 1 year. After first enlargement, variable tumour behaviour can occur. New hypopituitarism in stable tumours is rare, challenging necessity of regular pituitary function assessment.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"680-690"},"PeriodicalIF":5.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overweight/obesity and gastrointestinal disease incidence in Denmark-a cohort study.","authors":"Sigrid Bjerge Gribsholt, Dóra Körmendiné Farkas, Peter Jepsen, Bjørn Richelsen, Henrik Toft Sørensen","doi":"10.1093/ejendo/lvaf077","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf077","url":null,"abstract":"<p><strong>Objective: </strong>Obesity is associated with various gastrointestinal (GI) conditions. Because of the epidemic rise of obesity, we examined associations between overweight/obesity and incidence of individual GI diseases.</p><p><strong>Design: </strong>Cohort study.</p><p><strong>Setting: </strong>Denmark, 1997-2018.</p><p><strong>Participants: </strong>Using nationwide healthcare registries, we identified All Danes ≥18 years with a hospital diagnosis of overweight/obesity. We created an age- and sex-matched general population comparison cohort.</p><p><strong>Exposure: </strong>A diagnosis code of overweight/obesity.</p><p><strong>Main outcomes and measures: </strong>We compared the incidence of hospital-diagnosed GI diseases from 1 year after overweight/obesity diagnosis.</p><p><strong>Results: </strong>We included 129 466 patients with overweight/obesity (70.9% female, median age 49.3 years). Their incidence rate of GI disease was 30.1 per 1000 person years (95% CI: 29.8-30.5) vs 16.7 (95% CI: 16.5-16.8) for comparators, yielding an adjusted hazard ratio (aHR) of 1.7 (95% CI: 1.7-1.7). The aHRs indicated elevated risk of all GI disease sub-types in the overweight/obesity cohort, including cholelithiasis: 2.8 (95% CI: 2.7-2.9), cholecystitis: 2.6 (95% CI: 2.4-2.8), acute pancreatitis: 2.2 (95% CI: 2.0-2.4), stomach ulcer: 2.0 (95% CI: 1.9-2.1), cirrhosis: 1.5 (95% CI: 1.3-1.7), and obesity-associated GI cancer: 1.2 (95% CI: 1.2-1.3). The aHR for any GI disease was 1.4 (95% CI: 1.4-1.5) in men and 1.9 (95% CI: 1.8-1.9) in women. Among patients 18 to <30 years, the aHR was 2.6 (95% CI: 2.5-2.7) vs 1.3 (95% CI: 1.3-1.4) among individuals ≥70 years.</p><p><strong>Conclusions and relevance: </strong>Overweight/obesity is a risk factor for a wide range of GI diseases and is expected to become an even greater clinical challenge in the future.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"192 5","pages":"540-548"},"PeriodicalIF":5.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-recurrent mutations and copy number changes predominate pituitary adenoma genomes.","authors":"Dipika R Mohan, Ticiana Paes, Jacobo Buelvas Mebarak, David M Meredith, Beatriz Soares, Victor Vaz, Rona S Carroll, Ursula B Kaiser, Timothy R Smith, Wenya L Bi, Antonio M Lerario, Ana Paula Abreu","doi":"10.1093/ejendo/lvaf086","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf086","url":null,"abstract":"<p><strong>Objective: </strong>Pituitary adenomas (PAs) are common neoplasms. Our current understanding of the molecular basis of PA formation is incomplete. Routine implementation of targeted genomics has enabled the discovery of rare, potentially clinically actionable events.</p><p><strong>Methods: </strong>We used a cancer-focused gene panel to sequence a cohort of 171 PAs from patients who underwent surgery at Brigham and Women's Hospital from 2012 to 2020.</p><p><strong>Results: </strong>We identified known genetic variants enriched in specific PA subtypes: GNAS (somatotroph) and USP8 (Cushing's disease). Total mutational burden did not vary across adenoma subtypes; most adenomas possessed a few non-recurrent mutations in various established oncogenes and tumor suppressors. In contrast, the burden of copy number alterations varied widely across adenoma subtypes and was associated with higher MIB1 labeling index. We identified frequent deletions spanning MEN1 in prolactinomas and silent corticotroph adenomas, and subtype-specific copy number changes including 16p, 16q alterations in somatotroph adenomas without GNAS mutations. Within the corticotroph lineage, adenomas leading to Cushing's disease had few copy number alterations while silent corticotroph adenomas had numerous.</p><p><strong>Conclusions: </strong>This study highlights a role for individualized genetic events in PA formation and suggests that divergent patterns of genomic instability may facilitate tumorigenesis even within the same lineage. Taken together, we demonstrate how gene panels may illuminate novel biology in endocrine tumors.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"192 5","pages":"590-602"},"PeriodicalIF":5.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy, safety, and insulin-like growth factor I of weekly somapacitan in children with growth hormone deficiency: 3-year results from REAL4.","authors":"Bradley S Miller, Joanne C Blair, Michael Højby Rasmussen, Jan Frystyk, Anders Krogh Lemminger, Aristides Maniatis, Jun Mori, Volker Böttcher, Ho-Seong Kim, Michel Polak, Reiko Horikawa","doi":"10.1093/ejendo/lvaf096","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf096","url":null,"abstract":"<p><strong>Objective: </strong>Somapacitan is a long-acting GH approved for once-weekly treatment of GH deficiency (GHD). This study aims to evaluate the efficacy and tolerability of somapacitan after 3 years of treatment and 2 years after switch from daily GH in children with GHD.</p><p><strong>Design: </strong>Randomized, multi-national, open-labelled, active-controlled parallel-group phase 3 trial, with a 52-week main phase and 3-year safety extension (NCT03811535).</p><p><strong>Methods: </strong>Treatment-naïve children with GHD were randomized (2:1) to continuous somapacitan (0.16 mg/kg/week; \"soma/soma\" group) or daily GH (Norditropin®; 0.034 mg/kg/day) followed by somapacitan (0.16 mg/kg/week; \"switch\" group).</p><p><strong>Results: </strong>Of 200 participants, 188 completed 3 years of treatment. Sustained growth was observed in both groups. At week 156, mean (SD) height velocity (HV) between weeks 104 and 156 was 7.4 (1.5) cm/year in the soma/soma group and 7.8 (1.4) cm/year in the switch group. At week 156, the soma/soma and switch groups had reached a mean (SD) height SD score (HSDS) of -0.95 (0.98) and -1.08 (0.93), respectively, and were approaching the mean mid-parental HSDS of -0.74 (for both groups). Mean total insulin-like growth factor I (IGF-I) SDS during year 3 was similar between groups and within normal range (-2.0 to +2.0). Bioactive IGF-I and bioactive IGF-I to IGF-I ratio were similar between groups. Somapacitan was well tolerated, with low proportions reporting injection-site reactions.</p><p><strong>Conclusions: </strong>Sustained efficacy and tolerability were observed for continuous somapacitan treatment for 3 years, and for 2 years after the switching from daily GH treatment. HSDS in both groups was approaching mean mid-parental HSDS.</p><p><strong>Clinical trial registration: </strong>NCT03811535.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"192 5","pages":"651-661"},"PeriodicalIF":5.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}