European Journal of Endocrinology最新文献

{"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}

{"title":"Age-related differences in the clinical features and management of pituitary apoplexy: a cohort study.","authors":"Esteban Cordero Asanza, Antonio Biroli, Carlos Pérez-López, Marta Araujo-Castro, Rosa Cámara, Fernando Guerrero-Pérez, Almudena Vicente, Cristina Lamas, Guillermo Serra, Ana Irigaray Echarri, M Dolores Ollero, Inmaculada González Molero, Rocío Villar-Taibo, María Dolores Moure Rodríguez, Pablo García Feijoo, Víctor Rodríguez Berrocal, Noelia Sánchez, Alba Gutiérrez Hurtado, Vanessa Capristan-Díaz, Andreu Simó-Servat, Marta Gallach, Eva Safont Pérez, Victoria González Rosa, Soralla Civantos Modino, Edelmiro Menéndez Torre, Anna Aulinas, Pedro Iglesias, Juan J Diez, Verónica Rodríguez-Hernández, Albert Puig-Pérez, Elisa Blangini, Ignacio Bernabéu, Cristina Álvarez-Escolá, Silvana Sarria-Estrada, Manel Puig-Domingo, Fuat Arikán Abelló, Elena Martínez-Sáez, Betina Biagetti","doi":"10.1093/ejendo/lvaf056","DOIUrl":"10.1093/ejendo/lvaf056","url":null,"abstract":"<p><strong>Background: </strong>Pituitary apoplexy (PA) is a rare and acute condition resulting from hemorrhage or infarction of the pituitary gland. This study aimed to assess clinical characteristics, management, and outcomes of PA in patients aged <65 and ≥65 years using data from a Spanish multicenter cohort.</p><p><strong>Methods: </strong>We conducted a retrospective, multicenter study (2010-2023) of 301 PA patients from 18 Spanish hospitals. Data were analyzed for differences in demographics, clinical presentation, treatment approach, and outcomes.</p><p><strong>Results: </strong>Patients aged ≥65 years (n = 116, 38.5%) had more comorbidities, compared to younger patients (n = 185, 61.5%). No significant differences were observed in clinical presentation, including PA Score and radiological findings except for higher frequency of cranial nerve palsy (46.2 vs. 64.9%; P = .02) in older patients. Surgical (n = 209), and conservative (n = 92) treatment rates were similar between groups (conservative: 29.9 younger vs. 32.8% older; P = .51). Histopathological analysis revealed more necrosis in patients aged ≥65 years (66.7 vs. 80.6%; P = .04). Surgical resection rates and outcomes including mortality were comparable across age groups.</p><p><strong>Conclusions: </strong>PA management and outcomes were comparable in younger and older patients, despite greater comorbidities and more severe symptoms in older individuals. Histopathological findings suggest potential age-related differences in tumor biology, warranting further research. MRI would be preferred for diagnosis, particularly in older patients, as ischemic necrotic PA may be undiagnosed without advanced imaging.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"356-363"},"PeriodicalIF":5.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700048","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":"High-intensity interval training improves insulin sensitivity in individuals with prediabetes.","authors":"Pernille Mensberg, Clarissa Frandsen, Christian S Carl, Emilie Espersen, Thomas Leineweber, Emil L Larsen, Heidi Storgaard, Kirstine Schlawitz, Torben H D Petersen, Jytte N Poulsen, Frederik Sørensen, Peter M Gørtz, Julie L Forman, Bente Kiens, Filip K Knop, Tina Vilsbøll","doi":"10.1093/ejendo/lvaf004","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf004","url":null,"abstract":"<p><strong>Objective: </strong>To examine the separate and combined effects of low-volume high-intensity interval training (HIIT) and walking compared with no training on insulin sensitivity and skeletal metabolic capacity in individuals with prediabetes.</p><p><strong>Design: </strong>Individuals were randomized to: (1) control (no exercise), (2) HIIT (3 × 20 s's cycle sprint 3 times weekly), (3) HIIT + walking (walking >10 000 steps/day), or (4) walking for 12 weeks.</p><p><strong>Methods: </strong>Insulin sensitivity was assessed by an oral glucose tolerance test at baseline and end-of-trial. Additionally, proteins important for mitochondria capacity and insulin sensitivity were measured in the vastus lateralis muscle.</p><p><strong>Results: </strong>Seventy sedentary individuals with prediabetes (women n = 36; age: 60.8 ± 11.3 years (mean ± SD); body mass index: 31.6 ± 4.4 kg/m2; fasting plasma glucose: 6.6 ± 0.8 mmol/L; glycated hemoglobin A1c 5.7 ± 0.4% (39.0 ± 4.3 mmol/mol) were included. Compared with control, peripheral insulin sensitivity (measured by the Cederholm index) was significantly improved with HIIT (estimated treatment difference [ETD]: 18.5% [95% confidence interval (CI): 7.4; 28.3%] and HIIT + walking [ETD: 15.7% (95% CI: 4.4; 25.6%)]), but not with walking alone (ETD: 9.4% [95% CI: -2.5; 19.9%]). Whole-body insulin sensitivity (measured by the Matsuda index) was significantly increased with HIIT + walking (ETD: 28.0% [95% CI: 10.3; 42.3%]) and walking alone (ETD: 42.3% [95% CI: 28.3; 53.5%]), but not with HIIT alone (ETD: 17.0% [95% CI: -4.0; 33.7%]). Protein expression of proteins involved in mitochondrial capacity in skeletal muscle and glucose uptake were most improved with HIIT + walking, and no significant effects were observed with walking alone.</p><p><strong>Conclusions: </strong>Twelve weeks of low-volume HIIT training can improve glucose control and induces adaptations in skeletal muscle important for metabolic health in individuals with prediabetes.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"192 4","pages":"456-465"},"PeriodicalIF":5.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991651","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":"Reassessing the role of the p.(Arg304Gln) missense AIP variant in pituitary tumorigenesis.","authors":"Paul Benjamin Loughrey, Nadira B Mothojakan, Donato Iacovazzo, Ankit Arni, Elena D Aflorei, Giorgio Arnaldi, Anne Barlier, Albert Beckers, Mariana F Bizzi, Philippe Chanson, Jakob Dal, Adrian F Daly, Mary N Dang, Alessia David, Matheus de Oliveira Andrade, Tobias Else, Marianne S Elston, Amy Evans, Francesco Ferrau, Simona Fica, Daniel Flanagan, Monica R Gadelha, Ashley B Grossman, Sonal Kapur, Bernard Khoo, Ajith V Kumar, Chandan Kumar-Sinha, Ronald M Lechan, Mark Ludman, Louise A Metherell, Dragana Miljic, Vishnou Mourougavelou, Madalina Musat, Gianluca Occhi, Martina Owens, Ionela Pascanu, Sergio V B Pinheiro, Serban Radian, Antonio Ribeiro-Oliveira, Christof Schöfl, Kashyap A Patel, Laura C Hernández-Ramírez, Márta Korbonits","doi":"10.1093/ejendo/lvaf044","DOIUrl":"10.1093/ejendo/lvaf044","url":null,"abstract":"<p><strong>Objective: </strong>Heterozygous germline loss-of-function variants in AIP are associated with young-onset growth hormone and/or prolactin-secreting pituitary tumours. However, the pathogenic role of the c.911G > A; p.(Arg304Gln) (R304Q) AIP variant has been controversial. Recent data from public exome/genome databases show this variant is not infrequent. The objective of this work was to reassess the pathogenicity of R304Q based on clinical, genomic, and functional assay data.</p><p><strong>Design: </strong>Data were collected on published R304Q pituitary neuroendocrine tumour cases and from International Familial Isolated Pituitary Adenoma Consortium R304Q cases (n = 38, R304Q cohort). Clinical features, population cohort frequency, computational analyses, prediction models, presence of loss-of-heterozygosity, and in vitro/in vivo functional studies were assessed and compared with data from pathogenic/likely pathogenic AIP variant patients (AIPmut cohort, n = 184).</p><p><strong>Results: </strong>Of 38 R304Q patients, 61% (23/38) had growth hormone excess, in contrast to 80% of AIPmut cohort (147/184, P < .001). R304Q cohort was older at disease onset and diagnosis than the AIPmut cohort (median [quartiles] onset: 25 y [16-35] vs 16 y [14-23], P < .001; median [quartiles] diagnosis: 36 y [24-44] vs 21 y [15-29], P < .001). R304Q is present in gnomADv2.1 (0.31%) and UK Biobank (0.16%), including three persons with homozygous R304Q. No loss-of-heterozygosity was detected in four R304Q pituitary neuroendocrine tumour samples. In silico predictions and experimental data were conflicting.</p><p><strong>Conclusions: </strong>Evidence suggests that R304Q is not pathogenic for pituitary neuroendocrine tumour. We recommend changing this variant classification to likely benign and do not recommend pre-symptomatic genetic testing of family members or follow-up of already identified unaffected individuals with the R304Q variant.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"385-397"},"PeriodicalIF":5.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604461","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}