European Journal of Endocrinology最新文献

{"title":"Locally advanced pheochromocytoma/paraganglioma exhibit high metastatic recurrence and disease specific mortality rates: long-term follow-up of 283 patients.","authors":"Wolfgang Raber, Andreas Scheuba, Rodrig Marculescu, Harald Esterbauer, Johannes Rohrbeck","doi":"10.1093/ejendo/lvaf104","DOIUrl":"10.1093/ejendo/lvaf104","url":null,"abstract":"<p><strong>Importance: </strong>Data on locally advanced (LAP) pheochromocytoma/paraganglioma (PPGL), based on capsular, vascular or periadrenal fat invasion, tumor emboli and extra-adrenal extension, are scarce.</p><p><strong>Objective: </strong>To compare outcomes of patients with LAP and without (nLAP).</p><p><strong>Design: </strong>Retrospective cohort study, 1981-2024, prospectively supplemented 2020-2024.</p><p><strong>Setting: </strong>Referral center.</p><p><strong>Outcomes: </strong>Overall, metastatic and nonmetastatic recurrence, overall (OAS) and disease-specific survival (DSS).</p><p><strong>Results: </strong>Of 283 patients followed for 11.3 ± 8.8 (mean ± SD) years, 79 (27.9%) had LAP. Compared to patients with nLAP (n = 204), patients with LAP had more overall (n = 17 vs. 31, hazard ratio 2.4, 95% CI 1.4-5.0) and metastatic (11 vs. 9, HR 6.8, 2.2-20.6) and similar (6 vs. 22, HR 1.2, 0.5-3.0) nonmetastatic recurrences. OAS was comparable (12 vs. 42 nonsurvivors, HR 1.2, 0.6-2.3), but mortality from metastatic disease was higher with LAP (2 vs. 4 deaths, HR 12.2, 1.8-82.8). Extra-adrenal tumor location was predictive of metastatic and nonmetastatic recurrence but not of OAS or DSS, tumor size of metastatic recurrence and of DSS, cluster 1 and 2 pathogenic variants of overall and nonmetastatic recurrence but not of OAS or DSS. LAP with tumor emboli and extra-adrenal extension predicted overall (HR 4.5, 1.3-14.2 and 5.0, 1.4-13.7) and metastatic recurrence (HR 24.6, 6.4-91.8 and 6.5, 1.6-23.4), OAS (HR 21.2, 2.8-108, tumor emboli only) and DSS (HR 22.6, 3.5-183 and 13.1, 1.7-120), LAP with vessel invasion nonmetastatic recurrence (HR 3.6, 1.2-10.0).</p><p><strong>Conclusion: </strong>Patients with LAP vs. nLAP have higher metastatic recurrences and worse DSS. Tumor emboli and extra-adrenal extension indicated lower DSS, warranting a close follow-up.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"705-716"},"PeriodicalIF":5.3,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110118","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":"Genetic Origin of Multifocal Sporadic Medullary Thyroid Cancer and C Cell Hyperplasia.","authors":"Jacqueline Fátima Martins de Almeida, Cristina Romei, Teresa Ramone, Roberta Casalini, Raffaele Ciampi, Beatrice Fuochi, Francesca Signorini, Clara Ugolini, Virginia Cappagli, Laura Sterian Ward, Rossella Elisei","doi":"10.1093/ejendo/lvaf109","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf109","url":null,"abstract":"<p><strong>Objective: </strong>Sporadic medullary thyroid cancer (sMTC) mostly presents as a single lesion, but additional tumor foci may be present. The present study aimed to analyze the mutation profile of different tumor foci of multifocal sMTC to verify whether they represent an intra-organ metastatic dissemination or if they are independent tumors. Moreover, the genetics of C-cell hyperplasia (CCH) associated with sMTC was studied to verify whether CCH could be considered preneoplastic or reactive lesions.</p><p><strong>Methods: </strong>Thirty-eight multifocal sMTCs and 15 sMTCs with associated CCH were included: a total of 106 tumor foci and 25 different CCH areas were studied. The mutational status was analyzed by Next-Generation-Sequencing and/or droplet-digital PCR.</p><p><strong>Results: </strong>Thirty-one/38 (81.6%) sMTCs had a somatic mutation in the main tumor, while 7/38 (18.4%) cases were negative. Thirty/31 (96.8%) mutated sMTCs had a single mutation, while 3 different mutations were detected in one case (3.2%). Twenty-eight/31 (90%) mutated sMTCs showed the same mutation profile in the main tumors and in all secondary foci, while three cases were discordant. Eleven/15 (73.4%) sMTC with CCH showed a somatic mutation in the main tumor, while 4 (26.6%) were negative. Only 1/11 (9%) mutated cases showed the same mutation in the main tumor and in the CCH.</p><p><strong>Conclusions: </strong>Our data demonstrates that multiple foci of sMTC share the same driver mutation as the main tumor and support the hypothesis that they are intrathyroidal metastases. Most of the CCH associated with sMTC should not be considered a preneoplastic lesion as they are negative for the mutation of the main sMTC.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thyroid volume - new reference values for defining thyroid enlargement.","authors":"Till Ittermann, Aniela Angelow, Jean-François Chenot, Henry Völzke, Margit Heier, Birgit Linkohr, Annette Peters, Christine Meisinger, Simone Kiel","doi":"10.1093/ejendo/lvaf108","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf108","url":null,"abstract":"<p><strong>Objective: </strong>Upper reference values for thyroid volume are 25 ml for men and 18 ml for women. Thyroid volume alters with age, body weight, body height and iodine status, which is not considered in the current limits. The aim was to develop reference equations, considering age, body weight and height to calculate individual reference values for thyroid volume.</p><p><strong>Design: </strong>This cross-sectional study, used data from three independent cohorts (SHIP-START, SHIP-TREND, KORA-F4) in Germany. SHIP-START-0, a population-based health survey carried out in Northern Germany, from 1997-2001. SHIP-TREND-0, a second independent sample of the same study region, carried out between 2008-2012. KORA F4, a population-based health survey, conducted between 2006-2008 in Southern Germany.</p><p><strong>Methods: </strong>A total of 11,549 individuals (51% women) were included in data analysis. 8,606 individuals (45% women) were used as the thyroid-healthy reference population, when developing equations. Sex-stratified quantile regression models for the 95th percentile using age, body weight and height as explanatory variables, were performed.</p><p><strong>Results: </strong>Overall reference value for men was 38.7 ml, for women 28.6 ml. According to the established cut-offs, 34% of the overall population would have had goitre compared to 7% when using our equations.</p><p><strong>Conclusion: </strong>Upper reference values for thyroid volume are too low for an adult, previously iodine deficient population and do not consider age, body weight and height. Using individualised equations reduces the prevalence of thyroid enlargement substantially and can lead to a decrease in overdiagnoses and use of medical resources.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157492","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":"Response to commentary: Strengthening Endocrinology Training: Integrating Non-Clinical Competencies, Patient and Trainee Perspectives for Better Implementation Strategies.","authors":"Anton Luger, Maeve Durkan, Mirjam Christ-Crain, Pedro Marques","doi":"10.1093/ejendo/lvaf111","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf111","url":null,"abstract":"","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141697","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":"Strengthening Endocrinology Training: Integrating Non-Clinical Competencies, Patient and Trainee Perspectives for Better Implementation Strategies.","authors":"Amynta Arshad, Kashish Malhotra, Punith Kempegowda","doi":"10.1093/ejendo/lvaf110","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf110","url":null,"abstract":"","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136059","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":"Adolescent PCOS in South-East Asia: (epi)genetic origins of a hotspot.","authors":"Francis de Zegher, Lourdes Ibáñez","doi":"10.1093/ejendo/lvaf107","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf107","url":null,"abstract":"","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126504","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":"Ketone supplementation acutely lowers androgen and glucose levels in women with polycystic ovary syndrome (PCOS): A randomised clinical trial.","authors":"N Rittig, M C Arlien-Søborg, M V Svart, H H Thomsen, K Kirkegaard, V H Greve, M M Nielsen, K Stochholm, M J Ornstrup, C H Gravholt","doi":"10.1093/ejendo/lvaf106","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf106","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is a common endocrine disorder linked to insulin resistance and elevated androgens. While ketogenic diets reduce androgen and glucose levels in women with PCOS, the direct role of β-hydroxybutyrate (BHB) remains unclear. This study aimed to determine whether BHB supplementation acutely lowers circulating androgen and glucose levels in women with PCOS.</p><p><strong>Methods: </strong>A randomized, placebo-controlled crossover trial was conducted involving 20 women diagnosed with PCOS. Participants underwent fasting blood sampling on two occasions. They were randomly assigned to receive either a ketone supplement or a taste-matched placebo. Each intervention was administered over 10 hours, with one dose administered the evening before and another two hours prior to blood collection.</p><p><strong>Results: </strong>Following BHB supplementation, blood D-β-hydroxybutyrate (D-BHB) levels reached 2.4±1.2 mM, compared to 0.1±0.1 mM in the control group (p<0.001). Androgen concentrations were generally lower with BHB supplementation, with mean reductions in testosterone (-13%, CI 95%: -27 to 1, p=0.067), free testosterone (-21%, 95% CI: -43 to 1%, p=0.057), androstenedione (-14%, CI 95%: -29 to 0, p=0.050), and 11-ketotestosterone (-21%, CI 95%: -38 to -4, p=0.020) compared to control. Fasting plasma glucose levels were 4.6±0.7 mM after BHB supplementation, versus 5.1±0.4 mM in the placebo group (mean -10%, CI 95%: -5 to -15%, p<0.001).</p><p><strong>Conclusion: </strong>Ketone supplementation acutely lowers androgen and glucose levels in women with PCOS. These findings highlight the potential for ketone-based therapies as a novel treatment for PCOS and suggest the need for long-term clinical trials to further explore these effects.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110152","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":"Prevalence and clinical associations of USP8 variants in corticotroph tumours: a systematic review and aggregate data meta-analysis of 2171 cases.","authors":"Luis G Perez-Rivas, Vivian von Selzam, Prajina Sharma, Martin Reincke, Marily Theodoropoulou","doi":"10.1093/ejendo/lvaf097","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf097","url":null,"abstract":"<p><strong>Objective: </strong>Somatic USP8 variants are common in corticotroph tumours, but their reported prevalence and association with clinical characteristics vary widely among publications.</p><p><strong>Aim of the study: </strong>To determine the prevalence and clinical relevance of USP8 variants based on published evidence.</p><p><strong>Design and methods: </strong>Systematic review and meta-analysis of existing literature. We used PubMed, Embase and Web of Science databases. Inclusion criteria: original studies including ≥5 patients with Cushing's disease reporting genetic USP8 status. Exclusion criteria: no human research, unclear USP8 information, case reports (<5 patients). A random effects model meta-analysis and meta-regression were conducted. Studies reporting functional corticotroph tumours and also silent/non-functioning tumours were not excluded.</p><p><strong>Results: </strong>From 6782 extracted records, 44 studies summarizing 51 records were included in our meta-analysis (total n=2171 cases, 692 with USP8 variants). Pooled prevalence was 31.1% (95% CI 26.5-36.0%) and was higher in cases with functional tumours (34.1%; 95% CI 29.4%-39.1%). Patients with USP8 variants were mostly female (OR 4.52, 95%CI 3.39-6.02), and in average 4.47 years younger at diagnosis (95%CI 2.28-6.65 years younger). USP8 status was associated with higher odds for postoperative remission (OR 1.76, 95%CI 1.18-2.63) and for recurrence (OR 2.38, 95%CI 1.03-5.48). There was no clear evidence of association with any other clinical or tumour variable included in our analysis, mostly due to heterogeneity among studies. Meta-regression analysis showed that the variability in the prevalence of USP8 variants among studies was related to female/male ratio (adjusted R2=0.301), but not to other variables, such as tumour size or invasion.</p><p><strong>Conclusion: </strong>the present meta-analysis shows that patients with USP8 variant tumours are mostly female, diagnosed at younger age, more likely to achieve postoperative remission, but at higher risk of recurrence than those with tumours carrying the reference allele.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110123","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":"Hyperandrogenaemia, polycystic ovary syndrome, and physical fitness in women-a Northern Finland birth cohort study.","authors":"Katri Tuorila, Emilia Pesonen, Meri-Maija Ollila, Elisa Hurskainen, Marjukka Nurkkala, Raija Korpelainen, Maisa Niemelä, Laure Morin-Papunen, Terhi T Piltonen","doi":"10.1093/ejendo/lvaf080","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf080","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the independent associations of hyperandrogenaemia (HA) and polycystic ovary syndrome (PCOS) with physical fitness in women among the general population.</p><p><strong>Design: </strong>A population-based birth cohort study including 5889 women.</p><p><strong>Methods: </strong>Longitudinal associations of serum testosterone (T), free androgen index (FAI), and PCOS with cardiorespiratory fitness (CRF) (measured by heart rate after a submaximal exercise test) and grip strength over the 31 to 46 years of age timespan were examined using multivariable linear mixed models adjusted for time, body mass index, homeostatic model assessment of insulin resistance, physical activity and smoking. The results are reported as regression coefficients (β) with corresponding 95% confidence intervals [95% CI].</p><p><strong>Results: </strong>The third and fourth T and FAI quartiles were associated positively with higher heart rate after the submaximal exercise test in multivariable models indicating poorer CRF compared with women in Q1 of T and FAI (Q3: β of T = 1.58 [95% CI: 0.21 to 2.96], β of FAI = 1.97 [0.54 to 3.39]; Q4: β of T = 1.88 [0.46 to 3.30], β of FAI = 2.70 [1.15 to 4.25]). The second, third, and fourth quartiles of FAI were associated with higher grip strength in multivariable models compared with women in Q1 (Q2: β = 0.59 [0.04 to 1.14], Q3: β = 0.74 [0.16 to 1.30], Q4: β = 0.68 [0.06 to 1.27]). Excluding women with PCOS did not alter these results, while PCOS itself was not associated with CRF or grip strength.</p><p><strong>Conclusion: </strong>Hyperandrogenaemia in premenopausal women was associated with poorer CRF but better grip strength, independently of PCOS, which suggests that HA, rather than PCOS, has an independent and complex association with physical fitness in premenopausal women.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"192 5","pages":"519-528"},"PeriodicalIF":5.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974218","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":"Genetic predisposition to adiposity, and type 2 diabetes: the role of lifestyle and phenotypic adiposity.","authors":"Mengrong Zhang, Joey Ward, Rona J Strawbridge, Jana J Anderson, Carlos Celis-Morales, Jill P Pell, Frederick K Ho, Donald M Lyall","doi":"10.1093/ejendo/lvaf084","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf084","url":null,"abstract":"<p><strong>Aims: </strong>Genetic predisposition to adiposity is associated with type 2 diabetes (T2D), even in the absence of phenotypic adiposity (obesity and central obesity). We aimed to quantify the overall contribution of obesity and modifiable lifestyle factors to the association between genetic predisposition to adiposity and the development of T2D.</p><p><strong>Methods: </strong>This prospective cohort study involved 220 703 White British participants from the UK Biobank. It examined the associations between genetic predisposition to adiposity [body mass index polygenic risk (BMI-PRS) and waist-hip ratio polygenic risk (WHR-PRS)] and incident T2D, as well as interactions and mediation via lifestyle factors (diet quality, physical activity levels, total energy intake, sleep duration, and smoking and alcohol intake) and phenotypic adiposity.</p><p><strong>Results: </strong>People with high phenotypic adiposity and high adiposity PRS values (>1 SD above the mean) had the highest risk of incident T2D (versus non-obese/central obese and non-high PRS). This was the case for BMI-PRS [hazard ratio (HR) = 3.72] and WHR-PRS (HR = 4.17). Lifestyle factors explained 30.5% of the BMI-PRS/T2D association (2.0% mediation; 28.5% effect modification), and lifestyle and obesity together explained 92.1% (78.8% mediation; 13.3% effect modification). Lifestyle factors explained 20.4% of the WHR-PRS/T2D association (3.4% mediation; 17.0% effect modification), and lifestyle and central obesity together explained 72.8% (41.1% mediation; 31.7% effect modification).</p><p><strong>Conclusions: </strong>Whilst phenotypic adiposity explains a large proportion of the association between BMI-PRS/WHR-PRS and T2D, modifiable lifestyle factors also make contributions. Promoting healthy lifestyles among people prone to adiposity is important in reducing the global burden of T2D.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"192 5","pages":"549-557"},"PeriodicalIF":5.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12056655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976170","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}