European Journal of Endocrinology最新文献

{"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}

{"title":"Should anti-Müllerian hormone be a diagnosis criterion for polycystic ovary syndrome? An in-depth review of pros and cons.","authors":"Emídio Vale-Fernandes, Duarte Pignatelli, Mariana P Monteiro","doi":"10.1093/ejendo/lvaf062","DOIUrl":"10.1093/ejendo/lvaf062","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology (PCOM). Despite the widespread use of the Rotterdam criteria, challenges in diagnostic accuracy persist. Anti-Müllerian hormone (AMH), a glycoprotein secreted by ovarian follicles, has emerged as a promising biomarker for refining diagnosis due to its strong correlation with follicular count and elevated levels in women with PCOS. This review critically evaluates the advantages and limitations of incorporating AMH into PCOS diagnostic criteria. Elevated AMH levels are indicative of PCOM and anovulation, offering a non-invasive diagnostic tool that minimizes interobserver variability in ultrasound-based assessments. Additionally, AMH remains stable throughout the menstrual cycle and aligns with phenotypic diversity in PCOS, potentially supporting individualized management strategies. However, significant challenges remain. Variability in AMH assay methods, the absence of comparable cut-off values, and influences of age, ethnicity, and obesity on AMH levels limit its universal applicability. Additionally, AMH cut-offs for PCOS diagnosis, ranging from 3.5 to 5 ng/mL, raises questions about its clinical relevance, as there is not clear evidence of its biological significance. The review also highlights AMH's clinical utility in reproductive medicine, particularly in predicting ovarian response to stimulation, tailoring gonadotropin dosages, and optimizing assisted reproductive technology outcomes. While AMH holds promise as a complementary diagnostic criterion for PCOS, its fully integration into clinical practice requires further validation through standardized assays, population-specific cut-offs, and robust studies to address existing limitations. In conclusion, AMH harbours the potential to enhance the specificity and sensitivity of PCOS diagnosis, particularly in dubious cases. However, the inclusion of AMH in the current criteria for diagnosing PCOS still requires addressing methodological challenges and balancing its benefits against inherent limitations.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"R29-R43"},"PeriodicalIF":5.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788180","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":"How ready are endocrine scientists to share retrospective clinical data for research: a perspective from the European Network for the Study of Adrenal Tumors.","authors":"Antoan Stefan Sojat, Bastien Rance, Antoine Neuraz, Martin Fassnacht, Felix Beuschlein, Mercedes Robledo, Michaela Luconi, Dimitra Vassiliadi, Anthony Stell, Peter Igaz, Bogdan Dugic, Ljiljana V Marina, Anita Burgun, Darko Kastelan, Guillaume Assie","doi":"10.1093/ejendo/lvaf005","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf005","url":null,"abstract":"<p><strong>Objective: </strong>Individual patients' data sharing requires interoperability, security, ethical, and legal compliance. The aim was to assess the landscape and sharing capacities between endocrine researchers.</p><p><strong>Design: </strong>A standardized survey (SurveyMonkey®) with 67 questions was sent to European Network for the Study of Adrenal Tumors centers.</p><p><strong>Methods: </strong>Answers were counted as absolute numbers and percentages. Comparisons between inclusiveness target countries (ITC) and non-ITC (defined by Cooperation in Science & Technology Action) were performed using Fisher's exact test.</p><p><strong>Results: </strong>Seventy-three centers from 34 countries answered the survey. Electronic health record (EHR) systems are now the main source of data (90%). However, significant variability was reported, entailing >35 EHR providers, and variable data collected. Variable stakeholders' implication for enabling data sharing was reported, with more lawyers (P = .023), patient representatives (P < .001), ethicists (P = .002), methodologists (P = .023), and information technology experts (P < .001) in non-ITC centers. Implication of information technologies experts for data collection and sharing was underwhelming (33%). Funding for clinical research was higher in non-ITC than in ITC for clinical trials (P = .01) and for registry-based and cohort studies (P = .05). However, for retrospective studies addressing a specific clinical question, the funding was either very low (<10%) or nonexistent for both ITC and non-ITC (37% and 46%, respectively), with no dedicated funding for information technology (86%) and ethical and regulatory aspects (88%).</p><p><strong>Conclusions: </strong>In the absence of dedicated funding for retrospective research, current requirements for data sharing are obstacles.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"192 4","pages":"491-509"},"PeriodicalIF":5.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970326","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":"Neurophysin I: a reliable, novel, and robust biomarker for oxytocin.","authors":"Cihan Atila, Andi Nikaj, Svenja Leibnitz, Matthias E Liechti, Mirjam Christ-Crain","doi":"10.1093/ejendo/lvaf078","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf078","url":null,"abstract":"<p><strong>Introduction: </strong>Oxytocin (OXT) deficiency is a recently identified novel psycho-neuroendocrine entity associated with anxiety and reduced prosocial behavior. However, diagnosis and clinical progress have been hindered by challenges in reliably measuring OXT. Neurophysin I (NP-I), an equimolarly co-released cleavage product of the OXT precursor peptide, offers a promising alternative biomarker due to its stability, although it requires validation.</p><p><strong>Materials/methods: </strong>Analysis of a double-blind, placebo-controlled, cross-over study including 15 patients with hypothalamic-posterior-pituitary dysfunction and 15 healthy controls matched according to age (±3), sex, body mass index (±2), and menopause/hormonal contraceptives. Participants received a single oral dose of the strong OXT stimulator 3,4-methylenedioxymethamphetamine (MDMA, 100 mg) and placebo in random order, with a wash-out period of 2 weeks between both experimental sessions. NP-I and OXT levels were measured at 6 time points over 5 h after drug intake. Subjective drug effects were assessed using visual analog scales ranging from 0 = \"not at all\" to 100 = \"extremely,\" or were bidirectionally ranging from -50 to +50 mm, with 0 being the neutral measure = \"no effect.\" The primary endpoint-net incremental area under the curve (AUC) of NP-I from 0 to 300 min-was analyzed using a linear mixed-effects model.</p><p><strong>Results: </strong>In healthy controls, MDMA induced an 8-fold increase in OXT (peak: 624 pM [235-959]) and a 20-fold increase in NP-I (peak: 1508 pM [911-2233]). In contrast, in patients, MDMA induced no notable increase in OXT (peak: 92 pM [79-110]) and only a mild increase in NP-I (peak: 263 pM [140-300]). The AUC of NP-I after MDMA was 2279 pM·5 h [1087-3696] and 97 pM·5 h [50-241] in healthy controls and patients, respectively, with a significant difference (2340 pM·5 h (95% CI, 1462-3218; P < .0001). NP-I increase correlated with OXT increase (R = 0.92) and increases in subjective effects, eg, \"good effect,\" \"liking effect,\" \"feeling high,\" \"trust,\" and \"fear reduction\" (all R > 0.5).</p><p><strong>Conclusion: </strong>These results validate NP-I as a biomarker for endogenous OXT secretion after stimulation with MDMA, addressing long-standing challenges in direct OXT measurement. NP-I offers novel opportunities for research in conditions where reduced OXT levels or disruptions in signaling are implicated, such as autism spectrum disorder, anxiety, and depression.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"192 4","pages":"502-510"},"PeriodicalIF":5.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992592","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":"Germline-derived GNAS-Gsα variants associated with both gain-of-function and loss-of-function phenotypes.","authors":"Atilano Carcavilla, Arrate Pereda, Mami Miyado, Maki Fukami, Fumiko Kato, Toru Sengoku, Kazuhiro Ogata, María Clemente, Irene Valenzuela, Giovanna Mantovani, Marco Cappa, Paolo Cavarzere, Yerai Vado, Isabel González-Casado, Tsutomu Ogata, Guiomar Perez de Nanclares","doi":"10.1093/ejendo/lvaf006","DOIUrl":"10.1093/ejendo/lvaf006","url":null,"abstract":"<p><strong>Objective: </strong>Heterozygous germline inactivating mutations in GNAS can cause hormonal resistance, while activating mutations, usually somatic, result in constitutive cyclic adenosine monophosphate (cAMP) stimulation. Recent research has described germline activating variants leading to nephrogenic syndrome of inappropriate antidiuresis (NSIAD). The present study aims to characterise 4 families with an unusual combination of symptoms indicative of loss of Gsα function and a tendency to hyponatraemia compatible with NSIAD.</p><p><strong>Design: </strong>Clinical, genetic, structural, and functional characterization of GNAS variants identified.</p><p><strong>Methods: </strong>We performed GNAS sequencing followed by in vitro functional studies by dual luciferase assays and protein structural analyses of the identified variants and the previously described GNAS variant c.166A>T, p.(Ile56Phe), and correlated these data with clinical manifestations.</p><p><strong>Results: </strong>Genetic tests identified 2 heterozygous variants in GNAS: c.592C>T p.(Leu198Phe) in 1 family and c.501C>G p.(Asn167Lys) in other 2. Parental analyses revealed that the variants had been maternally inherited. One of the mothers, with the variant in her paternal allele, presented NSIAD. The baseline luciferase studies in the arginine vasopressin receptor 2 (AVPR2)-AVP system revealed mildly but significantly higher activity for p.(Ile56Phe) and p.(Asn167Lys) than for wildtype (WT), while statistical significance for p.(Leu198Phe) was not reached. Parathyroid hormone (PTH)-stimulated luciferase activity was lower for the 3-variant Gsα proteins than for WT-Gsα. Protein structural analyses suggest that the 3 variants could have distinct effects on the interactions with AVPR2 and PTH 1 receptor.</p><p><strong>Conclusions: </strong>This study provides further evidence in favour of the existence of germline variants that can cause clinical manifestations of both gain and loss of Gsα function.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"192 4","pages":"364-372"},"PeriodicalIF":5.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763509","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":"Gender-affirming hormone therapy and its impact on myocardial mass and cardiac function: a prospective magnetic resonance cohort study on transgender men and women.","authors":"Carola Deischinger, Dorota Slukova, Lana Kosi-Trebotic, Jürgen Harreiter, Stephan Nopp, Ivica Just, Radka Klepochova, Martin Krššák, Siegfried Trattnig, Ulrike Kaufmann, Alexandra Kautzky-Willer","doi":"10.1093/ejendo/lvaf057","DOIUrl":"10.1093/ejendo/lvaf057","url":null,"abstract":"<p><strong>Objective: </strong>Differences in cardiac parameters such as myocardial mass, left ventricular ejection fraction (LVEF), cardiac output, and brain natriuretic peptide (NT-proBNP) levels between cisgender men and women are well established. No evidence exists regarding changes in myocardial mass or cardiac function parameters in transgender individuals undergoing gender-affirming hormone therapy (GAHT).</p><p><strong>Design, setting, participants, and main outcomes: </strong>A prospective study enrolling transgender individuals under GAHT (20 individuals assigned female at birth [AFAB] and 15 assigned male at birth [AMAB]) was conducted at the Medical University of Vienna from 2019 to 2022. A 3-Tesla electrocardiogram-gated magnetic resonance imaging measured myocardial mass, LVEF, and other cardiac function parameters before GAHT and at 6-month follow-up. Myocardial lipid content was quantified using magnetic resonance spectroscopy.</p><p><strong>Results: </strong>In AFAB, myocardial mass increased significantly after 6 months of GAHT from mean (±SD) 48 (±8) g/m2 at baseline to 54 (±7) g/m2 at follow-up (P = .011). Individuals assigned male at birth showed a nonsignificant decrease of 4 (±14) g/m2 in myocardial mass. In both groups, no significant changes were noted in LVEF, stroke volume, cardiac output, or peak filling rate. Neither testosterone (AFAB: r = -0.127, P = .679; AMAB: r = -0.127, P = .679) nor estradiol levels (AFAB: r = -0.154, P = .616; AMAB: r = -0.154, P = .616) nor body mass index was related to myocardial mass at follow-up. Brain natriuretic peptide levels in AFAB were significantly reduced at follow-up (from median [IQR] 41 [26-57] to 19 [12-34] pg/mL).</p><p><strong>Conclusions: </strong>Myocardial mass increased, while NT-proBNP levels decreased significantly in AFAB after 6 months of GAHT. However, no significant changes in cardiac function were noted in AMAB and AFAB.</p><p><strong>Registration: </strong>ClinicalTrials.gov: NCT06245681 (registered 07 February 2024, https://classic.clinicaltrials.gov/ct2/show/NCT06245681).</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"429-436"},"PeriodicalIF":5.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735643","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":"Big data determination and validation of reference range for 24-h urine cortisol by liquid chromatography-mass spectrometry.","authors":"Gregory A Kline, Erik S Venos, David Campbell, Alexander A Leung, Dennis Orton","doi":"10.1093/ejendo/lvaf054","DOIUrl":"10.1093/ejendo/lvaf054","url":null,"abstract":"<p><strong>Objective: </strong>Twenty-four-hour urine-free cortisol (UFC) is a first-line test for Cushing syndrome (CS). A new mass spectrometry assay for UFC requires a validated, relevant reference range appropriate to a screening population.</p><p><strong>Design: </strong>Combined retrospective and prospective cohort study in a government health system and tertiary endocrinology clinic, Canada. Participants were patients with potential features of CS.</p><p><strong>Methods: </strong>The refineR reference interval algorithm was used to derive a middle 95%ile reference interval from 4830 UFC results in non-CS patients, compared with 120 prospective patients where evaluation excluded CS.</p><p><strong>Results: </strong>Urine-free cortisol and 24-h urine volume were correlated (r = 0.28, P < .0001). There was no significant difference between the volume-corrected UFC distributions in the prospective vs retrospective populations (P = .09). Urine-free cortisol distribution was highly skewed (P < .0001) and showed strong sex interaction. The refineR-generated adult male UFC upper reference limit was 238 nmol/day (86.3 μg/day) and for females was 147 nmol/day (53.3 μg/day); urine volume-corrected, the upper limits were 89 nmol/L (32.3 μg/L) and 91 nmol/L (32.9 μg/L), respectively. Applied to both populations, between 3% and 8% of all results would be flagged high; most are expected to represent nonneoplastic (pseudo)Cushing's.</p><p><strong>Conclusions: </strong>We used mass population data, where the prevalence of CS was likely very rare, plus a carefully phenotyped sample where CS was considered but excluded, to derive a validated reference interval for 24-h UFC by mass spectrometry in populations that reflect real-world use of the test. Given the highly skewed upper tail of the population distribution, it is probable that high test specificity for CS will require multimodality diagnostic confirmation.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"327-334"},"PeriodicalIF":5.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647652","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":"Letter to the editor: sociodemographic, lifestyle, and medical factors associated with calculated free testosterone concentrations in men: individual participant data meta-analyses.","authors":"Judith A P Bons, Jacquelien J Hillebrand, Annemieke C Heijboer","doi":"10.1093/ejendo/lvaf075","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf075","url":null,"abstract":"","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"192 4","pages":"L19-L20"},"PeriodicalIF":5.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973287","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}