European Journal of Endocrinology最新文献

{"title":"Metabolic syndrome in childhood, adolescent, and young adult cancer survivors: recommendations for surveillance from the International Late Effects of Childhood Cancer Guideline Harmonization Group.","authors":"Selina R van den Oever, Renée L Mulder, Kevin C Oeffinger, Jourik A Gietema, Roderick Skinner, Louis S Constine, W Hamish Wallace, Saro Armenian, Dana Barnea, Edit Bardi, Fabiën N Belle, Austin L Brown, Wassim Chemaitilly, Liz Crowne, Elvira C van Dalen, Christian Denzer, Matthew J Ehrhardt, Francesco Felicetti, Danielle N Friedman, Joy Fulbright, Adam W Glaser, Aleksander Giwercman, Hege Sangstuen Haugnes, Samah Hayek, Ulrike Hennewig, Marry M van den Heuvel-Eibrink, Riccardo Haupt, Laura van Iersel, Kala Kamdar, Joop Lefrandt, Gill Levitt, Vera Morsellino, Daniel A Mulrooney, Robert D Murray, Sebastian Neggers, Kirsten K Ness, Kristen A Neville, Nora L Nock, Maria Otth, Pinki K Prasad, Hanneke M van Santen, Christina Schindera, Shoshana R Rath, Julia Steinberger, Monica Terenziani, Mitra Varedi, Thomas Walwyn, Christina Wei, Melissa M Hudson, Leontien C M Kremer, Janine Nuver, Emily Tonorezos","doi":"10.1093/ejendo/lvaf046","DOIUrl":"10.1093/ejendo/lvaf046","url":null,"abstract":"<p><strong>Objective: </strong>Survivors of childhood, adolescent, and young adult (CAYA) cancer have an increased risk of metabolic syndrome (MetS). MetS describes the clustering of cardiovascular risk factors including overweight or obesity, hypertension, (pre)diabetes, and dyslipidaemia. While associated cardiovascular sequelae can be serious, MetS is preventable, manageable, and potentially reversible with the appropriate pharmacological and/or behavioral interventions. To optimize health outcomes in CAYA cancer survivors, international, harmonized surveillance recommendations are essential.</p><p><strong>Design: </strong>Systematic review and guideline development.</p><p><strong>Methods: </strong>A multidisciplinary guideline panel evaluated concordances and discordances across national guidelines for MetS surveillance and performed a systematic literature review. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the available evidence and formulate recommendations considering the strength of the underlying evidence as well as potential harms and benefits associated with MetS surveillance. In case evidence was lacking, recommendations were based on expert opinion. In addition, recommendations for surveillance modalities were derived from existing guidelines for MetS components where applicable.</p><p><strong>Results: </strong>The systematic literature review included 20 studies and highlighted 2 high-risk groups, namely CAYA cancer survivors treated with total body irradiation and those treated with cranial or craniospinal irradiation (moderate-quality evidence). Recommendations were formulated for MetS surveillance in these risk groups, covering preferred screening modalities, age at screening initiation, and surveillance frequency.</p><p><strong>Conclusions: </strong>In this international surveillance guideline for MetS in CAYA cancer survivors, we provide evidence-based recommendations for clinical practice, with the aim of ensuring optimal MetS surveillance for CAYA cancer survivors.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"S27-S40"},"PeriodicalIF":5.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656463","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":"Circulating miR-20a-5p as a biomarker associated with cabergoline responsiveness in patients with hyperprolactinemia and pituitary adenomas.","authors":"Yang Jong Lee, Jae Won Hong, Yongjae Kim, Jisup Kim, Chan Woo Kang, Min-Ho Lee, Ju Hyung Moon, Eui Hyun Kim, Cheol Ryong Ku, Eun Jig Lee","doi":"10.1093/ejendo/lvaf025","DOIUrl":"10.1093/ejendo/lvaf025","url":null,"abstract":"<p><strong>Objective: </strong>Dopamine agonist (DA) treatment is effective for hyperprolactinemia and reduces tumor size in patients with prolactinoma; however, prolonged DA administration without prolactinoma causes fibrosis around tumor tissues. Therefore, we aimed to identify circulating microRNAs (miRNAs) as potential biomarkers to predict prolactinoma in patients with hyperprolactinemia and pituitary tumors.</p><p><strong>Design: </strong>Plasma samples were collected from 3 comparison groups: (1) patients clinically diagnosed with prolactinoma vs nonfunctioning pituitary adenoma (NFPA) based on response to cabergoline treatment, (2) patients with surgically confirmed prolactinoma vs NFPA, and (3) patients before and after cabergoline treatment. Candidate miRNAs from the initial nCounter assay were validated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in a larger cohort of 247 patients with hyperprolactinemia and 37 controls.</p><p><strong>Methods: </strong>The nCounter assay was used for miRNA expression profiling, and the qRT-PCR validated the candidate miRNAs in the plasma and tumor tissue samples. Total RNA sequencing was conducted on pituitary tumor tissues to identify transcriptomic alterations. Furthermore, candidate miRNA target genes and their biological roles were analyzed using prolactinoma cell lines.</p><p><strong>Results: </strong>Three miRNA candidates (miR-20a-5p, miR-424-5p, and miR-514a-5p) were selected by analyzing 3 sets of expression comparisons between the 2 groups. Furthermore, the relative miR-20a-5p expression significantly increased in prolactinoma compared with that in normal pituitary glands, NFPA, growth hormone-secreting pituitary adenoma, and adrenocorticotropic hormone-secreting pituitary adenoma. In MMQ and GH4 cells, miR-20a-5p inhibition decreased prolactinoma cell proliferation and prolactin secretion.</p><p><strong>Conclusions: </strong>Circulating miR-20a-5p is a potential biomarker for prolactinoma, which could be associated with responsiveness to DAs.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"192 4","pages":"335-345"},"PeriodicalIF":5.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763506","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":"Differential cardiovascular risks of menopausal hormone therapy: insights from a Korean cohort.","authors":"Qingbo Li, Zhibao Sun, Wencheng Xu","doi":"10.1093/ejendo/lvaf040","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf040","url":null,"abstract":"","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"192 4","pages":"L17-L18"},"PeriodicalIF":5.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062971","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":"Identification of hypertension subtypes using microRNA profiles and machine learning.","authors":"Smarti Reel, Parminder S Reel, Josie Van Kralingen, Casper K Larsen, Stacy Robertson, Scott M MacKenzie, Alexandra Riddell, John D McClure, Stelios Lamprou, John M C Connell, Laurence Amar, Alessio Pecori, Martina Tetti, Christina Pamporaki, Marek Kabat, Filippo Ceccato, Matthias Kroiss, Michael C Dennedy, Anthony Stell, Jaap Deinum, Paolo Mulatero, Martin Reincke, Anne-Paule Gimenez-Roqueplo, Guillaume Assié, Anne Blanchard, Felix Beuschlein, Gian Paolo Rossi, Graeme Eisenhofer, Maria-Christina Zennaro, Emily Jefferson, Eleanor Davies","doi":"10.1093/ejendo/lvaf052","DOIUrl":"10.1093/ejendo/lvaf052","url":null,"abstract":"<p><strong>Objective: </strong>Hypertension is a major cardiovascular risk factor affecting about 1 in 3 adults. Although the majority of hypertension cases (∼90%) are classified as \"primary hypertension\" (PHT), endocrine hypertension (EHT) accounts for ∼10% of cases and is caused by underlying conditions such as primary aldosteronism (PA), Cushing's syndrome (CS), pheochromocytoma or paraganglioma (PPGL). EHT is often misdiagnosed as PHT leading to delays in treatment for the underlying condition, reduced quality of life and costly, often ineffective, antihypertensive treatment. MicroRNA (miRNA) circulating in the plasma is emerging as an attractive potential biomarker for various clinical conditions due to its ease of sampling, the accuracy of its measurement and the correlation of particular disease states with circulating levels of specific miRNAs.</p><p><strong>Methods: </strong>This study systematically presents the most discriminating circulating miRNA features responsible for classifying and distinguishing EHT and its subtypes (PA, PPGL, and CS) from PHT using 8 different supervised machine learning (ML) methods for the prediction.</p><p><strong>Results: </strong>The trained models successfully classified PPGL, CS, and EHT from PHT with area under the curve (AUC) of 0.9 and PA from PHT with AUC 0.8 from the test set. The most prominent circulating miRNA features for hypertension identification of different disease combinations were hsa-miR-15a-5p and hsa-miR-32-5p.</p><p><strong>Conclusions: </strong>This study confirms the potential of circulating miRNAs to serve as diagnostic biomarkers for EHT and the viability of ML as a tool for identifying the most informative miRNA species.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"418-428"},"PeriodicalIF":5.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656408","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":"Deleterious variants in intolerant genes reveal new candidates for self-limited delayed puberty.","authors":"Raíssa C Rezende, Wen He, Lena R Kaisinger, Antonio M Lerario, Evan C Schafer, Katherine A Kentistou, Priscila S Barroso, Nathalia L M Andrade, Naiara C B Dantas, Elaine Maria F Costa, Laurana P Cellin, Elisangela P S Quedas, Stephanie B Seminara, Rodolfo A Rey, Romina P Grinspon, Veronica Meriq, Ken K Ong, Ana Claudia Latronico, John R B Perry, Sasha R Howard, Yee-Ming Chan, Alexander A L Jorge","doi":"10.1093/ejendo/lvaf061","DOIUrl":"10.1093/ejendo/lvaf061","url":null,"abstract":"<p><strong>Objective: </strong>Self-limited delayed puberty (SLDP) is the most common cause of delayed puberty and exhibits high heritability, although few causal genes have been identified. This study aims to identify potential candidate genes associated with SLDP.</p><p><strong>Methods: </strong>Whole-exome sequencing was conducted in 71 children with SLDP, most of whom presented with short stature. Rare coding variants were prioritized through comprehensive bioinformatics analyses and classified as high-impact or moderate-impact based on predicted functional effects. Candidate genes were selected based on the absence of human phenotype data, recurrence within the cohort, intolerance to mutation, and prior identification in genome-wide association studies. Burden tests compared the frequency of rare high-impact variants in these candidate genes between SLDP patients and the gnomAD v2.0 control group. Gene-phenotype associations were further explored using UK Biobank data.</p><p><strong>Results: </strong>Fourteen high-impact and 7 moderate-impact variants were identified in 19 candidate genes, suggesting a potential role in SLDP. Variants in 8 candidate genes (GPS1, INHBB, SP3, NAMPT, ARID3B, NASP, FNBP1, PRDM2) were significantly enriched in cases compared to controls in the burden test analysis. INHBB was additionally linked to delayed menarche in UK Biobank data. Furthermore, 3 pathogenic variants (CDK13, GDF5, ANRKD11) and 6 likely pathogenic variants (TYMP, DPF2, KMT2C, TP63, MC3R, GHSR) previously associated with growth or pubertal human disorders were identified.</p><p><strong>Conclusion: </strong>These findings suggest that SLDP involves both monogenic and polygenic mechanisms, with novel candidate genes contributing to its genetic basis. The association of INHBB with pubertal timing underscores its potential role in SLDP pathophysiology.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"481-490"},"PeriodicalIF":5.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12013340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802662","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":"Impaired accuracy of the dexamethasone suppression test after bariatric surgery: implications for post-surgical cortisol interpretation.","authors":"Anna Casteràs, Enzamaria Fidilio, Marta Comas, Alba Zabalegui, Vanesa Flores, Marina Giralt, Noelia Díaz-Troyano, Roser Ferrer, Ramon Vilallonga, Andreea Ciudin, Betina Biagetti","doi":"10.1093/ejendo/lvaf053","DOIUrl":"10.1093/ejendo/lvaf053","url":null,"abstract":"<p><strong>Importance: </strong>The impact of bariatric surgery (BS) on the performance of the 1 mg dexamethasone suppression test (DST) is not well established.</p><p><strong>Objective: </strong>(1) To evaluate the intraindividual results of the DST in a group of patients before and 2 years after BS, and (2) to assess plasma dexamethasone levels and other factors influencing the reliability of the DST.</p><p><strong>Methods: </strong>We conducted a prospective longitudinal study, including 38 subjects evaluating DST before and 2 years after BS. We also compared DST results, plasma dexamethasone levels, and related factors across 3 groups: individuals of the previous cohort 2 years post-BS (n = 21), patients with severe obesity without BS (pwO; n = 10), and healthy controls (n = 7).</p><p><strong>Results: </strong>Post-BS patients had higher cortisol levels after DST compared with prior (0.9 vs 0.7 µg/dL; P < .01). Four individuals post-BS had cortisol levels >1.8 µg/dL in the absence of autonomous cortisol secretion. Plasma dexamethasone levels were significantly lower in post-BS patients (1.9 ng/dL) compared with non-operated pwO (3.7 ng/dL) and healthy controls (4.0 ng/mL), P < .01. Multivariate analysis identified BS (β = -1.258, P = .01) and sex hormone-binding globulin levels (β = -.013, P = .04) as significant independent predictors of plasma dexamethasone concentrations.</p><p><strong>Conclusion: </strong>Post-BS subjects showed higher post-DST cortisol levels and reached lower plasma dexamethasone concentration compared with non-operated individuals, which may lead to false-positive results. These findings highlight the need to consider dexamethasone measurements to enhance DST interpretation in post-BS patients. Further studies are necessary to validate these findings in broader populations. The underlying mechanisms need to be explored.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"192 4","pages":"346-355"},"PeriodicalIF":5.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763511","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":"Cardiovascular status in chronic hypoparathyroidism: a systematic cross-sectional assessment in 168 patients.","authors":"Carmina Teresa Fuss, Karen Gronemeyer, Franca Hermes, Marcus Dörr, Benedikt Schmid, Caroline Morbach, Lena Schmidbauer, Nicolas Schlegel, Martin Fassnacht, Ann Cathrin Koschker, Peter Nordbeck, Anke Hannemann, Stefanie Hahner","doi":"10.1093/ejendo/lvaf023","DOIUrl":"10.1093/ejendo/lvaf023","url":null,"abstract":"<p><strong>Objective: </strong>Long-term complications such as renal diseases are well known in patients with chronic hypoparathyroidism (hypoPT), but risk of cardiovascular comorbidity remains less clear. This study comprehensively assessed cardiovascular parameters in hypoPT compared to matched controls.</p><p><strong>Design: </strong>Cross-sectional cohort study involving 168 patients with chronic hypoPT.</p><p><strong>Methods: </strong>Patients underwent electrocardiograms, blood pressure measurements, and echocardiography. A 1:3 propensity score matching was performed with individuals from the German population-based Study of Health in Pomerania (SHIP-TREND) and the \"Characteristics and Course of Heart Failure Stages A-B\" (STAAB) cohort.</p><p><strong>Results: </strong>HypoPT showed significantly higher systolic (128 vs 125 mm Hg, P = .02) and diastolic blood pressures (83 vs 77 mm Hg, P < .01). Intake of antihypertensives was similar between groups. The QTc interval was markedly prolonged (438 vs 420 ms, P < .01) with QTc interval prolongation occurring significantly more frequently in hypoPT (24% vs 6%, P < .01). Interestingly, echocardiography revealed significantly lower left ventricular mass index (28 vs 43 g/m2.7, P < .01) and less frequent left ventricular hypertrophy (7%% vs 41%, P < .01) in hypoPT but comparable left ventricular ejection fraction (P = .48). HypoPT patients had higher prevalence of mitral (20 vs 0%, P < .01) and aortic valve stenoses (7 vs 2%, P < .01). Comparison with STAAB confirmed the increased prevalence of arterial hypertension and reduced myocardial mass indices.</p><p><strong>Conclusions: </strong>Patients with hypoPT exhibit a higher prevalence of QTc interval prolongation despite established therapy and an increased incidence of hypertension. Conversely, echocardiography revealed lower left ventricular mass and less frequent left ventricular hypertrophy in hypoPT, but higher prevalence of valve stenosis. Regular monitoring of hypertension, QTc interval prolongation, and valve stenosis is recommended to reduce the risk of cardiovascular diseases.</p><p><strong>Clinical trial registration number: </strong>NCT05585593.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"192 4","pages":"373-384"},"PeriodicalIF":5.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763490","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":"Mortality in Cushing's syndrome: declining over 2 decades but remaining higher than the general population.","authors":"Amit Akirov, Maria Fleseriu, Hiba Masri-Iraqi, Tzipora Shochat, Shiri Kushnir, Ilan Shimon, Yaron Rudman","doi":"10.1093/ejendo/lvaf059","DOIUrl":"10.1093/ejendo/lvaf059","url":null,"abstract":"<p><strong>Objective: </strong>Patients with endogenous Cushing's syndrome (CS) have elevated mortality, particularly during active disease. A recent meta-analysis reported reduced mortality rates after 2000 in adrenal CS and Cushing disease (CD), though many studies lacked population-matched controls.</p><p><strong>Methods: </strong>Nationwide retrospective study (2000-2023) in Israel using the Clalit Health Services database to assess all-cause mortality in patients with endogenous CS matched 1:5 with controls by age, sex, socioeconomic-status, and body mass index (BMI). Primary outcome was all-cause mortality. Secondary outcomes included cause-specific mortality, impact of hypercortisolism remission, disease source, and mortality risk factors.</p><p><strong>Results: </strong>The cohort included 609 cases with CS (mean age 48.1 ± 17.2 years; 65.0% women) and 3018 matched controls (47.9 ± 17.2 years; 65.4% women). Over a median follow-up of 16 years, 133 cases (21.8%) and 472 controls (15.6%) died (HR = 1.44, 95% CI, 1.19-1.75). Both patients with CD (HR = 1.73, 95% CI, 1.27-2.36) and adrenal CS (HR = 1.31, 95% CI, 1.00-1.81) had increased mortality risk. Patients without remission within 2 years had a higher mortality risk than those achieving remission (HR = 1.44, 95% CI, 1.00-2.17). Mortality was similar for CD and adrenal CS (HR = .83, 95% CI, .56-1.24). Older age, male gender, and prior malignancy were independent risk factors for mortality.</p><p><strong>Conclusion: </strong>This is the largest national cohort study on mortality risk in CS over the past 2 decades, showing a significantly higher risk compared to matched controls in a homogeneous database. While etiology had no impact, remission significantly affected mortality, highlighting the importance of disease control for long-term survival.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"445-455"},"PeriodicalIF":5.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771642","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":"Identification of metabolite biomarkers for pancreatic neuroendocrine tumours using a metabolomic approach.","authors":"Arnaud Jannin, Sophie Dabo-Niang, Christine Do Cao, Amandine Descat, Stéphanie Espiard, Catherine Cardot-Bauters, Marie-Christine Vantyghem, Benjamin Chevalier, Jean François Goossens, Benjamin Marsac, Jimmy Vandel, Sophie Dominguez, Robert Caiazzo, François Pattou, Camille Marciniak, Medhi El Amrani, Isabelle Van Seuningen, Nicolas Jonckheere, Anne-Frédérique Dessein, Lucie Coppin","doi":"10.1093/ejendo/lvaf055","DOIUrl":"10.1093/ejendo/lvaf055","url":null,"abstract":"<p><strong>Importance: </strong>Metabolic flexibility, a key hallmark of cancer, reflects aberrant tumour changes associated with metabolites. The metabolic plasticity of pancreatic neuroendocrine tumours (pNETs) remains largely unexplored. Notably, the heterogeneity of pNETs complicates their diagnosis, prognosis, and therapeutic management.</p><p><strong>Objective: </strong>Here, we compared the plasma metabolomic profiles of patients with pNET and non-cancerous individuals to understand metabolic dysregulation.</p><p><strong>Design, setting, participants, intervention and measure: </strong>Plasma metabolic profiles of 76 patients with pNETs and 38 non-cancerous individuals were analyzed using LC-MS/MS and FIA-MS/MS (Biocrates AbsoluteIDQ p180 kit). Statistical analyses, including univariate and multivariate methods, were performed along with the generation of receiver operating characteristic (ROC) curves for metabolomic signature identification.</p><p><strong>Results: </strong>Compared with non-cancerous individuals, patients with pNET exhibited elevated levels of phosphoglyceride metabolites and reduced acylcarnitine levels, indicating an upregulation of fatty acid oxidation (FAO), which is crucial for the energy metabolism of pNET cells and one-carbon metabolism metabolites. Elevated glutamate levels and decreased lipid metabolite levels have been observed in patients with metastatic pNETs. Patients with the germline MEN1 mutations showed lower amino acid metabolites and FAO, with increased metabolites related to leucine catabolism and lipid metabolism, compared to non-MEN1 mutated patients. The highest area under the ROC curve was observed in patients with pNET harbouring MEN1 mutations.</p><p><strong>Conclusion and relevance: </strong>This study highlights the distinct plasma metabolic signatures of pNETs, including the critical role of FAO and elevated glutamate levels in metastasis, supporting the energy and biosynthetic needs of rapidly proliferating tumour cells. Mapping of these dysregulated metabolites may facilitate the identification of new therapeutic targets for pNETs management.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"466-480"},"PeriodicalIF":5.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656339","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":"Urea-stimulated copeptin: a novel diagnostic approach in polyuria polydipsia syndrome.","authors":"Sven Lustenberger, Cihan Atila, Juliana Baumgartner, Sophie Monnerat, Julia Beck, Joyce Santos de Jesus, Mirjam Christ-Crain","doi":"10.1093/ejendo/lvaf058","DOIUrl":"10.1093/ejendo/lvaf058","url":null,"abstract":"<p><strong>Background: </strong>Distinguishing arginine vasopressin (AVP) deficiency from primary polydipsia remains challenging. While hypertonic saline-stimulated copeptin testing offers high diagnostic accuracy, it is complex and limited to specialized centers. Intravenous urea is known to stimulate AVP secretion, but the effect of oral urea on copeptin levels is unknown.</p><p><strong>Methods: </strong>Twenty-two healthy adults were included in a randomized, double-blind, placebo-controlled cross-over trial receiving a single dose of urea (0.5 g/kg; minimum 30 g, maximum 45 g) and placebo. Serum copeptin was measured at 30-min intervals for 2.5 h. In a second step, 13 patients with AVP-deficiency and 13 patients with primary polydipsia were included in an open-label pilot study, receiving urea only. The primary endpoint was maximum copeptin within 150 min.</p><p><strong>Results: </strong>In healthy adults, median [IQR] copeptin significantly increased from 4.6 [3.0-5.7] pmol/L at baseline to a maximum of 10.1 [7.2-11.6] pmol/L at 120 min after ingestion of urea, while it remained stable at 3.8 [2.9-6.6] pmol/L after placebo intake (P < .001). In patients with AVP-deficiency, copeptin remained below detection limit throughout the test, while in patients with primary polydipsia the peak was seen 150 min after ingestion of urea at 7.4 pmol/L [4.3, 10.3]. The best copeptin cut-off for differentiating AVP-deficiency from primary polydipsia was 3.5 pmol/L after 120 min, with 93% sensitivity and specificity.</p><p><strong>Conclusion: </strong>Oral urea stimulates copeptin in healthy adults and patients with primary polydipsia, but not in patients with AVP-deficiency, establishing the first oral copeptin-based test in differentiating primary polydipsia from AVP-deficiency.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"437-444"},"PeriodicalIF":5.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763488","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}