European Journal of Endocrinology最新文献

{"title":"Real-life experience on efficacy and safety of setmelanotide treatment in prepubertal children.","authors":"Ahmet Kahveci, Ilknur Kurt, Serap Turan, Tulay Guran, Abdullah Bereket, Belma Haliloglu","doi":"10.1093/ejendo/lvaf008","DOIUrl":"10.1093/ejendo/lvaf008","url":null,"abstract":"<p><p>Monogenic obesity, characterized by severe, early-onset obesity due to single-gene defects, often resists traditional weight management strategies. This report presents real-life experiences on the efficacy and safety of setmelanotide, an MC4R agonist, in 4 prepubertal children (ages 3-9) with LEPR and POMC deficiencies. Findings indicate that setmelanotide is effective at lower doses in our patients with POMC deficiency (0.3-0.5 mg/day) than the patients with LEPR deficiency (2.5 mg/day). Treatment was generally well-tolerated, with injection site reactions and hyperpigmentation as common side effects. As novel findings, gonadotropin-related effects such as hypothalamo-pituitary-gonadal axis activation and testicular descent were observed in 2 patients. Growth deceleration was noted in 2 children, and recovery from central hypothyroidism in 1 patient with POMC deficiency. Overall, setmelanotide appears to be effective and well-tolerated in young children with monogenic obesity. However, further studies are necessary to evaluate the long-term effects of early intervention on growth and pubertal development.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"192 2","pages":"K15-K18"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074178","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":"Body composition and cardiometabolic risks of patients with adrenal tumours in relation to hormonal activity: a large cross-sectional single-centre study.","authors":"Jung Hee Kim, Han Na Jang, Seung Shin Park, Jeong Hee Yoon, Young Min Cho, Sang Joon Park, Jeong Min Lee, Ji Won Yoon","doi":"10.1093/ejendo/lvae167","DOIUrl":"10.1093/ejendo/lvae167","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to examine how different types of adrenal hormone excess influence body composition.</p><p><strong>Design: </strong>A retrospective, cross-sectional, single-centre study.</p><p><strong>Methods: </strong>We retrospectively enrolled 2971 consecutive adults with adrenal tumours and age-, sex-, and body mass index-matched controls at a 1:3 ratio. The area and attenuation of skeletal muscle and fat at the L3 vertebrae were measured using computed tomography-based analysis software. Prevalence ratios of cardiometabolic outcomes were calculated using the Poisson regression.</p><p><strong>Results: </strong>Patients with non-functioning adenoma (n = 1354) and mild autonomous cortisol secretion (MACS; n = 786) showed similar body compositions. Patients with overt Cushing's syndrome (CS) had the highest visceral fat (VF) area to skeletal muscle area ratio (1.14), while pheochromocytoma (PHEO) patients had the lowest (0.52). Muscle attenuation was lowest in CS and highest in PHEO (32.6 vs 41.5 Hounsfield units, P < .001). Mild autonomous cortisol secretion patients had higher risks of hypertension and dyslipidaemia than non-functioning adenoma patients. Non-functioning adenoma and MACS patients had higher VF area and lower muscle/fat attenuation compared with controls, while primary aldosteronism patients had body compositions similar to controls, except for higher fat attenuation.</p><p><strong>Conclusions: </strong>Adrenal tumours are associated with altered body composition. Even patients with non-functioning adenoma and MACS had increased VF area and lower muscle and fat attenuation compared with controls, indicating potential cardiometabolic risks.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"192 2","pages":"141-149"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556169","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":"Levothyroxine supplementation trials in preconception and pregnant women.","authors":"Rebecca Man, Rima Dhillon-Smith, Tim I M Korevaar","doi":"10.1093/ejendo/lvaf012","DOIUrl":"10.1093/ejendo/lvaf012","url":null,"abstract":"<p><p>Thyroid disorders are common in women of childbearing age, representing the second most prevalent endocrine disorder in this population. Low thyroid function preconception and during pregnancy has been associated with a range of adverse outcomes including subfertility, miscarriage, preterm birth, and ongoing health problems in the neonate. Levothyroxine (LT4) treatment is routinely used in women with overt hypothyroidism (OH) to achieve a euthyroid status and consequently reduce the risk of these adverse outcomes. However, in other groups, such as those with subclinical hypothyroidism (SCH) or thyroid autoimmunity, the evidence is less clear and subsequently guidelines differ in their recommendations. Here we explore key trials exploring the use of LT4 in different types of thyroid disorder, including OH, SCH, isolated hypothyroxinemia, and thyroid autoimmunity. We examine how these disorders are defined in different trials, the specifics of the populations included, and the varying timing and dosage of LT4. By exploring the limitations of these trials and the interactions between results, we highlight issues for future research and practical considerations for policy-makers and clinicians caring for women with low thyroid function during preconception and pregnancy.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"R7-R15"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406462","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":"KDM1A genetic alterations, a rare cause of primary bilateral macronodular adrenal hyperplasia, strongly associated with food-dependent Cushing's syndrome: results of its systematic germline screening in 301 index cases and genotype/phenotype correlation.","authors":"Lucas Bouys, Patricia Vaduva, Anne Jouinot, Florian Violon, Anna Vaczlavik, Maxime Barat, Helaine Charchar, Fanny Chasseloup, Crystal Kamilaris, Stéphanie Espiard, Magalie Haissaguerre, Gérald Raverot, Matthias Kroiss, Annabel Berthon, Karine Perlemoine, Igor Tauveron, Laurence Guignat, Rossella Libé, Lionel Groussin, Guillaume Assié, Eric Pasmant, Martin Reincke, Françoise Borson-Chazot, Amandine Ferrière, Marie-Christine Vantyghem, Constantine A Stratakis, Peter Kamenický, Maria Candida Barisson Villares Fragoso, Albain Chansavang, Bruno Ragazzon, Jérôme Bertherat","doi":"10.1093/ejendo/lvaf016","DOIUrl":"10.1093/ejendo/lvaf016","url":null,"abstract":"<p><strong>Objective: </strong>ARMC5 is the most prevalent gene predisposing to primary bilateral macronodular adrenal hyperplasia (PBMAH), but germline KDM1A variants have been identified in the rare PBMAH associated with food-dependent Cushing's syndrome (FDCS). The purpose of this work was to assess the frequency of KDM1A variants in a large series of PBMAH patients.</p><p><strong>Design: </strong>A total of 301 consecutive PBMAH index cases from 8 international endocrinology departments were included. Clinical, biological, and imaging data were collected retrospectively.</p><p><strong>Results: </strong>Ten (3.3%) patients carried a germline KDM1A pathogenic or likely pathogenic variant, 60 (19.9%) carried a germline ARMC5 alteration, and 231 (76.8%) had no identified genetic predisposition. Food-dependent Cushing's syndrome was present in all patients with KDM1A variants and absent in the 2 other groups. KDM1A patients had a higher 24-h urinary free cortisol (3.0-fold upper limit of normal vs 1.36 for ARMC5 patients and 0.66 for wild-type patients, respectively, P = .0001). In accordance with FDCS pathophysiology, patients with KDM1A variants had a lower morning fasting plasma cortisol (192 nmol/L vs 407 and 428, respectively, P = .0003) and a higher midnight plasma cortisol (487 nmol/L vs 297 and 171.96, respectively, P = .0004). Morning/midnight plasma cortisol ratio below 0.65 holds 100% sensitivity and specificity for the detection of FDCS. All patients with KDM1A variants were women, vs 65% of ARMC5 patients and 67% of wild-type patients (P = .0337).</p><p><strong>Conclusions: </strong>KDM1A germline pathogenic variants are rare in PBMAH and account for <5% of index cases. KDM1A seems constantly associated with FDCS, which can be evoked in front of a morning/midnight plasma cortisol ratio below 0.65.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"119-127"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373810","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":"The effect of first intervention on cardiac parameters in patients with acromegaly: a systematic review.","authors":"Kevin A Huynh, Jin Al-Gully, José M Montero-Cabezas, Linda E Scheffers, Marco J T Verstegen, Nienke R Biermasz, Eva C Coopmans","doi":"10.1093/ejendo/lvaf009","DOIUrl":"10.1093/ejendo/lvaf009","url":null,"abstract":"<p><strong>Objective: </strong>Cardiovascular disease in acromegaly patients remains a major cause of morbidity and all-cause mortality. This systematic review investigates the effect of the first growth hormone-lowering intervention on cardiac parameters.</p><p><strong>Design: </strong>Systematic review.</p><p><strong>Methods: </strong>Studies evaluating cardiac parameters following the first intervention in acromegaly published up to February, 25, 2022 were included in this systematic review. Risk of bias was assessed using a modified Newcastle-Ottawa Scale and Joanna Briggs Institute Critical Appraisal Checklist. Primary treatment modalities included (transsphenoidal) surgery and medical treatment with first-generation somatostatin receptor ligands. Cardiac outcome measures were divided into cardiac structure (left ventricular hypertrophy [LVH], [indexed] left ventricular mass [LVM/LVMi]) and cardiac function (left ventricular ejection fraction [LVEF] and E/A ratio).</p><p><strong>Results: </strong>Twenty-six studies (17 cohort studies and 9 case reports) were included out of 2541 potential studies. The risk of bias analysis categorized, 24 studies as low risk and 2 studies as intermediate risk. Disease-associated changes in cardiac structure and function generally improved in most studies following primary treatment. Left ventricular mass/left ventricular mass index significantly decreased in 9/15 studies and the prevalence of LVH in 3/13 studies. Left ventricular ejection fraction significantly increased in 9/14 studies and the E/A ratio in 6/7 studies. Despite the limited number of studies, cardiac structure improved more in patients achieving biochemical remission than in those failing to achieve biochemical remission.</p><p><strong>Conclusions: </strong>Acromegaly associated structural and functional myocardial changes improve with both medical and surgical treatment. Normalizing or even reducing growth hormone/insulin-like growth factor 1 levels may be key in the prevention of further progression of cardiac involvement in acromegaly and adverse cardiac outcomes.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"S1-S14"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064591","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":"Do adrenal incidentalomas have an impact on mental health? A comprehensive review.","authors":"Darko Kastelan, Tina Dusek","doi":"10.1093/ejendo/lvaf011","DOIUrl":"10.1093/ejendo/lvaf011","url":null,"abstract":"<p><p>Adrenal incidentalomas (AIs) are increasingly detected during imaging performed for conditions unrelated to adrenal pathology. Numerous studies have shown that the presence of AI is associated with a higher frequency of hypertension, type 2 diabetes, dyslipidemia, obesity, and osteoporosis. This increased morbidity is mostly related to mild autonomous cortisol secretion, which is the most common hormonal abnormality in these patients. It is well known that glucocorticoid excess affects the hippocampus and prefrontal cortex, brain structures involved in mood regulation and cognitive processes, leading to a wide range of psychiatric symptoms, including depression. While these effects are well documented in patients with Cushing's syndrome, data on mental health changes in patients with AIs remain scarce. Additionally, the few existing studies have several limitations, leaving important clinical questions unanswered. Consequently, the extent to which AIs are associated with impaired mental health and whether patients would benefit from surgical treatment remains unclear. Addressing these challenges is crucial for developing adequate management strategies. This review explores potential psychological and psychiatric implications of AIs. By synthesizing existing literature, we aim to explain the relationship between AIs and mental health disorders, providing a background for future research and clinical practice guidelines.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"R1-R6"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074172","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":"Association of menopausal hormone therapy with risk of cardiovascular disease in Korean women.","authors":"Jin-Sung Yuk, Gwang Sil Kim, Dong-Gil Kim, Young Sup Byun, Myoung-Hwan Kim, Sang-Hee Yoon, Gwan Hee Han, Byung Gyu Kim","doi":"10.1093/ejendo/lvae161","DOIUrl":"10.1093/ejendo/lvae161","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the association between various regimens and combinations of menopausal hormone therapy (MHT) and the risk of cardiovascular disease (CVD) in clinical practice.</p><p><strong>Design: </strong>This was a population-based cohort study.</p><p><strong>Methods: </strong>This population-based cohort study used data from the Health Insurance Review and Assessment Service. The data of women who reported entering menopause at ≥40 years of age with no history of CVD in the national health examination between 2011 and 2014 were extracted. A total of 134 298 pairs were included in the MHT and non-MHT groups after 1:1 propensity score matching. The participants were followed until December, 31, 2020.</p><p><strong>Results: </strong>During a median follow-up of 7.9 (IQR 6.9-8.9) years, the incidences of CVD were 146 per 100 000 person/year and 179 per 100 000 person/year for the non-MHT and MHT groups, respectively. After adjusting for covariates, MHT use was associated with an increased CVD risk (hazard ratio [HR], 1.22 [1.14-1.31]) compared with the non-MHT group; the risk was based on an increased risk of stroke and coronary artery revascularization. Tibolone (HR, 1.38, [1.27-1.50]) was associated with increased CVD, but estrogen alone or combined estrogen/progestogen was not. There was no difference in CVD risk, regardless of the type of estrogen agent used. For combined estrogen/progestogen therapy, dydrogesterone was associated with reduced CVD risk.</p><p><strong>Conclusions: </strong>There was an increased risk of CVD in MHT users. By regimen, tibolone use was associated with increased risk of CVD, whereas estrogen either alone or in combination with progestogen was not. There was no difference according to the type of estrogen. The type of progestogen seems to modify the results, since dydrogesterone was associated with reduced CVD risk.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"192 2","pages":"73-80"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079080","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":"Digital quantification of somatostatin receptor subtypes 2 and 5 in growth hormone-secreting pituitary tumors.","authors":"Claudia Campana, Jessica Amarù, Angelo Milioto, Federica Nista, Peter M van Koetsveld, Anand Iyer, Marica Arvigo, Diego Ferone, Leo J Hofland, Federico Gatto","doi":"10.1093/ejendo/lvae170","DOIUrl":"10.1093/ejendo/lvae170","url":null,"abstract":"<p><p>Immunohistochemistry (IHC) of somatostatin receptor subtype 2 can predict response to first-generation somatostatin receptor ligands (fg-SRLs) in acromegaly. Recently, we validated an open-source digital image analysis (DIA) to quantify somatostatin receptor subtype 2 (SSTR2) expression. We aimed to validate the DIA also on somatostatin receptor subtype 5 (SSTR5) in a new cohort of growth hormone (GH)-secreting pituitary tumors, with IHC performed in a different laboratory, and to correlate fg-SRL response with SSTs expression. Somatostatin receptor subtype 2 and SSTR5 were assessed in 42 GH-secreting pituitary tumors, using a semiquantitative immunoreactivity score (IRS) and the DIA by use of the open-access software CellProfiler. The DIA calculates the staining intensity and the percentage of positive cells (%PC). We found a good correlation between IRS and DIA for both SSTR2 and SSTR5 (P < .001), demonstrating the reliability of the DIA in this setting. Response to fg-SRL treatment correlated with SSTR2, but not SSTR5, expression. Somatostatin receptor subtype 2 expression predicted response to fg-SRL. In particular, the identified cut-offs were IRS ≥ 5 (area under the curve [AUC] 0.763; sensitivity 77%; specificity 83%); intensity/area ≥0.106 (AUC 0.833; sensitivity 92%; specificity 83%); and %PC-DIA ≥63.7% (AUC 0.917; sensitivity 92%; specificity 83%). The SSTR2 %PC correlated with treatment response only when evaluated using the DIA, showing a better performance of this method.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"K6-K14"},"PeriodicalIF":5.3,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871693","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 sex hormones on pheochromocytomas, paragangliomas, and gastroenteropancreatic neuroendocrine tumors.","authors":"Katharina Wang, Alessa Fischer, Umberto Maccio, Kathrin Zitzmann, Mercedes Robledo, Michael Lauseker, Jana Bauer, Nicole Bechmann, Simon Gahr, Julian Maurer, Lea Peischer, Astrid Reul, Hanno Nieß, Petra Zimmermann, Matthias Ilmer, Katharina Schilbach, Thomas Knösel, Matthias Kroiss, Martin Fassnacht, Simon A Müller, Gregoire B Morand, Alexander Huber, Diana Vetter, Kuno Lehmann, Zsolt Kulcsar, Hermine Mohr, Natalia S Pellegata, Constanze Hantel, Martin Reincke, Felix Beuschlein, Karel Pacak, Ashley B Grossman, Christoph J Auernhammer, Svenja Nölting","doi":"10.1093/ejendo/lvae163","DOIUrl":"10.1093/ejendo/lvae163","url":null,"abstract":"<p><strong>Objective: </strong>The effects of sex hormones remain largely unexplored in pheochromocytomas and paragangliomas (PPGLs) and gastroenteropancreatic neuroendocrine tumors (GEP-NETs).</p><p><strong>Methods: </strong>We evaluated the effects of estradiol, progesterone, Dehydroepiandrosterone sulfate (DHEAS), and testosterone on human patient-derived PPGL/GEP-NET primary culture cell viability (n = 38/n = 12), performed next-generation sequencing and immunohistochemical hormone receptor analysis in patient-derived PPGL tumor tissues (n = 36).</p><p><strong>Results: </strong>In PPGLs, estradiol and progesterone (1 µm) demonstrated overall significant antitumor effects with the strongest efficacy in PPGLs with NF1 (cluster 2) pathogenic variants. Estrogen receptor alpha (ERα) positivity was detected in 11/36 PPGLs, including 4/4 head-and-neck paragangliomas (HNPGLs). ERα-positive tumors responded with a significant cell viability decrease to estradiol. DHEAS and testosterone (1 µm) displayed no effects, but higher doses of testosterone (10 µm) demonstrated significant antitumor effects, including a pheochromocytoma lung metastasis with strong androgen receptor positivity (30%). Driven by the antitumor effects of estrogen, we evaluated G-protein-coupled estrogen receptor (GPER) agonist G-1 as a potential therapeutic option for PPGLs and found strong significant antitumor potential, with the strongest efficacy in tumors with NF1 pathogenic variants. Moreover, we detected sex-related differences-tumors from male patients showed significantly stronger responsivity to G-1 compared with tumors from female patients. In GEP-NETs, sex hormones showed overall no effects, especially no tumor growth-promoting effects.</p><p><strong>Conclusion: </strong>We provide novel data on the effects of elevated sex hormone levels, potentially seen during pregnancy or hormone replacement therapy, on PPGL/GEP-NET tumor growth. G-1 might offer a novel therapeutic approach for some PPGLs depending on patient's sex and the individual tumor's genetic/molecular background. All HNPGLs showed ERα positivity.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"192 1","pages":"46-60"},"PeriodicalIF":5.3,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978014","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":"Predicting type 2 diabetes and testosterone effects in high-risk Australian men: development and external validation of a 2-year risk model.","authors":"Kristy P Robledo, Ian C Marschner, Mathis Grossmann, David J Handelsman, Bu B Yeap, Carolyn A Allan, Celine Foote, Warrick J Inder, Bronwyn G A Stuckey, David Jesudason, Karen Bracken, Anthony C Keech, Alicia J Jenkins, Val Gebski, Meg Jardine, Gary Wittert","doi":"10.1093/ejendo/lvae166","DOIUrl":"10.1093/ejendo/lvae166","url":null,"abstract":"<p><strong>Objective: </strong>We have shown that men aged 50 years+ at high risk of type 2 diabetes treated with testosterone together with a lifestyle program reduced the risk of type 2 diabetes at 2 years by 40% compared to a lifestyle program alone. To develop a personalized approach to treatment, we aimed to explore a prognostic model for incident type 2 diabetes at 2 years and investigate biomarkers predictive of the testosterone effect.</p><p><strong>Design: </strong>Model development in 783 men with impaired glucose tolerance but not type 2 diabetes from Testosterone for Prevention of Type 2 Diabetes; a multicenter, 2-year trial of Testosterone vs placebo. External validation performed in 236 men from the Examining Outcomes in Chronic Disease in the 45 and Up Study (EXTEND-45, n = 267 357).</p><p><strong>Methods: </strong>Type 2 diabetes at 2 years defined as 2-h fasting glucose by oral glucose tolerance test (OGTT) ≥11.1 mmol/L. Risk factors, including predictive biomarkers of testosterone treatment, were assessed using penalized logistic regression.</p><p><strong>Results: </strong>Baseline HbA1c and 2-h OGTT glucose were dominant predictors, together with testosterone, age, and an interaction between testosterone and HbA1c (P = .035, greater benefit with HbA1c ≥ 5.6%, 38 mmol/mol). The final model identified men who developed type 2 diabetes, with C-statistics 0.827 in development and 0.798 in validation. After recalibration, the model accurately predicted a participant's absolute risk of type 2 diabetes.</p><p><strong>Conclusions: </strong>Baseline HbA1c and 2-h OGTT glucose predict incident type 2 diabetes at 2 years in high-risk men, with risk modified independently by testosterone treatment. Men with HbA1c ≥ 5.6% (38 mmol/mol) benefit most from testosterone treatment, beyond a lifestyle program.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"15-24"},"PeriodicalIF":5.3,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885328","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}