European Journal of Endocrinology最新文献

{"title":"Predicting type 2 diabetes and testosterone effects in high-risk Australian men: development and external validation of a 2-year risk model.","authors":"Kristy P Robledo, Ian C Marschner, Mathis Grossmann, David J Handelsman, Bu B Yeap, Carolyn A Allan, Celine Foote, Warrick J Inder, Bronwyn G A Stuckey, David Jesudason, Karen Bracken, Anthony C Keech, Alicia J Jenkins, Val Gebski, Meg Jardine, Gary Wittert","doi":"10.1093/ejendo/lvae166","DOIUrl":"10.1093/ejendo/lvae166","url":null,"abstract":"<p><strong>Objective: </strong>We have shown that men aged 50 years+ at high risk of type 2 diabetes treated with testosterone together with a lifestyle program reduced the risk of type 2 diabetes at 2 years by 40% compared to a lifestyle program alone. To develop a personalized approach to treatment, we aimed to explore a prognostic model for incident type 2 diabetes at 2 years and investigate biomarkers predictive of the testosterone effect.</p><p><strong>Design: </strong>Model development in 783 men with impaired glucose tolerance but not type 2 diabetes from Testosterone for Prevention of Type 2 Diabetes; a multicenter, 2-year trial of Testosterone vs placebo. External validation performed in 236 men from the Examining Outcomes in Chronic Disease in the 45 and Up Study (EXTEND-45, n = 267 357).</p><p><strong>Methods: </strong>Type 2 diabetes at 2 years defined as 2-h fasting glucose by oral glucose tolerance test (OGTT) ≥11.1 mmol/L. Risk factors, including predictive biomarkers of testosterone treatment, were assessed using penalized logistic regression.</p><p><strong>Results: </strong>Baseline HbA1c and 2-h OGTT glucose were dominant predictors, together with testosterone, age, and an interaction between testosterone and HbA1c (P = .035, greater benefit with HbA1c ≥ 5.6%, 38 mmol/mol). The final model identified men who developed type 2 diabetes, with C-statistics 0.827 in development and 0.798 in validation. After recalibration, the model accurately predicted a participant's absolute risk of type 2 diabetes.</p><p><strong>Conclusions: </strong>Baseline HbA1c and 2-h OGTT glucose predict incident type 2 diabetes at 2 years in high-risk men, with risk modified independently by testosterone treatment. Men with HbA1c ≥ 5.6% (38 mmol/mol) benefit most from testosterone treatment, beyond a lifestyle program.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"15-24"},"PeriodicalIF":5.3,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endocrine dysfunction in long-term survivors of pediatric head and neck rhabdomyosarcoma.","authors":"Michele Morfouace, Reineke A Schoot, Marinka L F Hol, Veronique Minard-Colin, Frederic Kolb, Stephanie Bollé, Matumba T Kayembe, Mark N Gaze, Eric Sandler, Rutger R G Knops, Johannes H M Merks, Ludwig E Smeele, Daniel J Indelicato, Olga Slater, Hanneke M van Santen","doi":"10.1093/ejendo/lvae168","DOIUrl":"https://doi.org/10.1093/ejendo/lvae168","url":null,"abstract":"<p><strong>Objective: </strong>Survivors of pediatric head and neck rhabdomyosarcoma (HNRMS) are at risk of developing endocrinopathies following local treatment, resulting from radiation damage to the pituitary gland, hypothalamus, or thyroid gland, often at a young age. Our aim was to determine the prevalence of endocrine dysfunction in long-term HNRMS survivors and compare the prevalence of anterior pituitary insufficiency (API) among different local treatment strategies: external beam radiation with photons, external beam radiation with protons, microscopically radical surgery combined with external irradiation, and macroscopic radical surgery combined with brachytherapy.</p><p><strong>Design and methods: </strong>Head and neck rhabdomyosarcoma survivors treated between 1993 and 2017, with ≥2 years of follow-up, without recurrent disease or secondary malignancy were eligible for this study. The presence of any endocrine dysfunction was assessed cross-sectionally using Common Terminology Criteria of Adverse Events grading, anthropometrics, and biochemical testing. Retrospective chart review was added to this clinical assessment.</p><p><strong>Results: </strong>Ninety-six survivors with long follow-up time (median, 9 years) were included. Any endocrinopathy was present in 35% of survivors, with 88% having pituitary, 6% peripheral (thyroid), and 6% combined insufficiencies. None had gonadal insufficiency. Growth hormone deficiency was diagnosed in 31 (32%) survivors, with additional pituitary insufficiencies in 12 (39%). In 8%, central precocious puberty preceded API. None of the survivors given brachytherapy had API.</p><p><strong>Conclusions: </strong>The prevalence of pituitary dysfunction in HNRMS survivors is high, emphasizing the importance of systematic endocrine assessment during follow-up, including pubertal development and growth. Efforts should be made to further reduce extraneous irradiation to endocrine organs to prevent dysfunction later in life.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"192 1","pages":"25-33"},"PeriodicalIF":5.3,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946619","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":"More than meets the eye: predicting adrenocortical carcinoma outcomes with pathomics.","authors":"Jianqiu Kong, Mingli Luo, Yi Huang, Ying Lin, Kaiwen Tan, Yitong Zou, Juanjuan Yong, Sha Fu, Shaoling Zhang, Xinxiang Fan, Tianxin Lin","doi":"10.1093/ejendo/lvae162","DOIUrl":"https://doi.org/10.1093/ejendo/lvae162","url":null,"abstract":"<p><strong>Background: </strong>Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy with high recurrence rates and poor prognosis. Current prognostic models are inadequate, highlighting the need for innovative diagnostic tools. Pathomics, which utilizes computer algorithms to analyze whole-slide images, offers a promising approach to enhance prognostic models for ACC.</p><p><strong>Methods: </strong>A retrospective cohort of 159 patients who underwent radical adrenalectomy between 2002 and 2019 was analyzed. Patients were divided into training (N = 111) and validation (N = 48) cohorts. Pathomics features were extracted using an unsupervised segmentation method. A pathomics signature (PSACC) was developed through LASSO-Cox regression, incorporating 5 specific pathomics features.</p><p><strong>Results: </strong>The PSACC showed a strong correlation with ACC prognosis. In the training cohort, the hazard ratio was 3.380 (95% CI, 1.687-6.772, P < .001), and in the validation cohort, it was 3.904 (95% CI, 1.039-14.669, P < .001). A comprehensive nomogram integrating PSACC and M stage significantly outperformed the conventional clinicopathological model in prediction accuracy, with concordance indexes of 0.779 versus 0.668 in the training cohort (P = .002) and 0.752 versus 0.603 in the validation cohort (P = .003).</p><p><strong>Conclusions: </strong>The development of a pathomics-based nomogram for ACC presents a superior prognostic tool, enhancing personalized clinical decision making. This study highlights the potential of pathomics in refining prognostic models for complex malignancies like ACC, with implications for improving prognosis prediction and guiding treatment strategies in clinical practice.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"192 1","pages":"61-72"},"PeriodicalIF":5.3,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052053","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":"Evaluating the predictive power of frailty and bone mineral density on fracture risk in rural older adults.","authors":"Liangping Zhang, Xizhuo Zhou, Shuqiang Cha","doi":"10.1093/ejendo/lvae134","DOIUrl":"10.1093/ejendo/lvae134","url":null,"abstract":"","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"L5-L6"},"PeriodicalIF":5.3,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461001","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: \"Primary hypophysitis and the benefits of glucocorticoids, a still unresolved question\".","authors":"Aysa Hacioglu, Zuleyha Karaca, Kursad Unluhizarci, Fahrettin Kelestimur","doi":"10.1093/ejendo/lvae165","DOIUrl":"10.1093/ejendo/lvae165","url":null,"abstract":"","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"L3-L4"},"PeriodicalIF":5.3,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853426","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: \"Primary\" hypophysitis and the benefits of glucocorticoids, a still unresolved question.","authors":"Léa Miquel, Benoit Testud, Frederic Castinetti","doi":"10.1093/ejendo/lvae164","DOIUrl":"10.1093/ejendo/lvae164","url":null,"abstract":"","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"L1-L2"},"PeriodicalIF":5.3,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881556","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":"Gonadal function and pathology in 17beta-HSD 3 and 5alpha-reductase deficiency.","authors":"Lidewij S Boogers, Hennie T Brüggenwirth, Katja P Wolffenbuttel, Remko Hersmus, Jillian Bryce, S Faisal Ahmed, Angela K Lucas-Herald, Federico Baronio, Martine Cools, Mona Ellaithi, Evgenia Globa, Tülay Güran, Olaf Hiort, Paul-Martin Holterhus, Kenneth MсElreavey, Marek Niedziela, Marianna Rita Stancampiano, Buşra G Tosun, Yolande van Bever, J Wolter Oosterhuis, Leendert H J Looijenga, Sabine E Hannema","doi":"10.1093/ejendo/lvae154","DOIUrl":"10.1093/ejendo/lvae154","url":null,"abstract":"<p><strong>Objective: </strong>17β-Hydroxysteroid dehydrogenase 3 deficiency (17β-HSDD) and 5α-reductase type 2 deficiency (5α-RD) are rare 46,XY differences of sex development (DSD). This study aims to enlarge the limited knowledge on long-term gonadal function and gonadal pathology in these conditions.</p><p><strong>Design: </strong>Retrospective multicentre cohort study.</p><p><strong>Methods: </strong>Data on phenotype, laboratory results, and hormone treatment were collected from patients aged ≥16 years at time of data collection with genetically confirmed 17β-HSDD and 5α-RD from 10 centres via the I-DSD Registry. If gonadectomy or gonadal biopsy had been performed, pathology reports and/or gonadal tissue or images were collected.</p><p><strong>Results: </strong>All 16 patients with 17β-HSDD were raised female; 1 (6%) changed to male gender at age 14. Three females were treated with gonadotrophin-releasing hormone agonists (GnRHa) to prevent virilisation. Thirteen underwent gonadectomy at median age 8 (range 0-17). None had germ cell (pre)malignancies. Of 14 patients with 5α-RD, 10 (71%) were raised female. Five changed gender at age 7-23, of whom 4 to male gender. One was treated with GnRHa. Six underwent gonadectomy at median age 10 (range 0-31). None had germ cell (pre)malignancies. With gonads in situ, puberty spontaneously progressed. Three were treated with dihydrotestosterone.</p><p><strong>Conclusions: </strong>A significant percentage of individuals with 17β-HSDD and 5α-RD changed gender, and some were treated with GnRHa to prevent virilisation before making a definitive decision about gonadectomy. When left in situ, spontaneous puberty occurs and germ cell (pre)malignancies seem uncommon at least until early adulthood. Together, these data support delaying a decision about gonadectomy until late adolescence in these conditions.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"192 1","pages":"34-45"},"PeriodicalIF":5.3,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946638","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":"Hypoglycaemia following physical exercise in a patient with novel SLC16A1 variant.","authors":"Ruth Frampton, David Lewis, Yusof Rahman, Michel Tchan, Jerry R Greenfield","doi":"10.1093/ejendo/lvae159","DOIUrl":"https://doi.org/10.1093/ejendo/lvae159","url":null,"abstract":"<p><p>Rare defects in the promoter region of SLC16A1, the gene encoding monocarboxylate transporter 1 (MCT-1), result in exercise-induced hyperinsulinism. In this disorder inappropriate insulin secretion is triggered by anaerobic exercise with consequent hypoglycaemia. We describe the case of a 41 year old man presenting with a generalised tonic clonic seizure and severe hypoglycaemia following strenuous exercise. A subsequent prolonged fast with incorporation of exercise into the protocol demonstrated hyperinsulinaemic hypoglycaemia; genetic testing revealed a variant of unknown significance in the SLC16A1 gene. Administration of subcutaneous octreotide resulted in dose dependent reduction in hyperinsulinaemia and hypoglycaemia.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881557","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":"Insights into the genetic landscape of pheochromocytomas and paragangliomas in a Brazilian cohort.","authors":"Gustavo F C Fagundes, Felipe Freitas-Castro, Lucas S Santana, Felipe L Ledesma, Janaina Petenuci, Ana Caroline F Afonso, Caio A A Pereira, Ana Alice W Maciel, Ibere C Soares, Nathalia L Gomes, Delmar M Lourenço, Maria Adelaide A Pereira, Victor Srougi, Fabio Y Tanno, Jose L Chambo, Maria Candida B V Fragoso, Ana O Hoff, Berenice B Mendonca, Ana Claudia Latronico, Madson Q Almeida","doi":"10.1093/ejendo/lvae160","DOIUrl":"https://doi.org/10.1093/ejendo/lvae160","url":null,"abstract":"<p><strong>Objective: </strong>Germline and somatic drivers are identified in 30% and 40% of pheochromocytomas and paragangliomas (PPGLs), respectively. In this study, we investigated the genetic landscape of PPGLs in a Brazilian cohort.</p><p><strong>Methods: </strong>We studied 182 index patients with PPGLs (116 females and 66 males), comprising 118 pheochromocytoma and 70 paraganglioma cases. Our optimized sequencing strategy included SANGER sequencing, targeted next-generation sequencing panel and whole exome sequencing.</p><p><strong>Results: </strong>Germline and somatic pathogenic or likely pathogenic variants in susceptibility genes were identified in 88 (48.4%) and 18 (10.4%) cases, respectively. SDHB was the most frequently affected gene, identified in 30 patients (16.5%), with a germline SDHB exon 1 deletion present in 46.7% of these cases. The Brazilian cohort exhibited a higher rate of germline diagnoses when compared to the European (31%), American (27%), and Chinese (21%) cohorts (p < 0.001). Five germline variants were identified: 1) Three CHEK2 likely pathogenic or pathogenic variants (c.475T>C/p.Tyr159His; c.362G>A/p.Cys121Tyr; c.319+2T>A); and 2) Two BRCA2 pathogenic variants (c.3680_3681delTG/p.Leu1227fs and c.7806-2A>C). These variants are unreported in the Brazilian genomic variant repository. CHEK2 immunostaining was negative in the three tumors, with one case exhibiting CHEK2 loss of heterozygosity. Moreover, the prevalence of CHEK2 or BRCA2 pathogenic or likely pathogenic variants in our cohort was significantly higher compared with to global population databases (p < 0.0001 and p = 0.0004, respectively).</p><p><strong>Conclusion: </strong>Our cohort of PPGLs demonstrated a high frequency of germline diagnoses. Additionally, our findings suggest CHEK2 and BRCA2 as potential susceptibility genes for PPGLs.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of childhood dehydroepiandrosterone sulfate concentration, pubertal development, and DNA methylation at puberty-related genes.","authors":"Maya Sudman, Reinhard Stöger, Gillian R Bentley, Philippa Melamed","doi":"10.1093/ejendo/lvae156","DOIUrl":"10.1093/ejendo/lvae156","url":null,"abstract":"<p><strong>Objective: </strong>High concentrations of dehydroepiandrosterone sulfate (DHEAS) often precede premature puberty and sometimes polycystic ovary syndrome (PCOS). We hypothesized that the underlying mechanisms might involve DNA methylation. As an indicator of the downstream effects of DHEAS, we looked for associations between prepubertal DHEAS concentration, pubertal progression, and DNA methylation at puberty-related genes in blood cells.</p><p><strong>Design: </strong>Blood methylome and DHEAS concentration at 7.5 and 8.5 years, respectively, were analyzed in 91 boys and 82 girls. Pubertal development data were collected between 8.1 and 17 years (all from UK birth cohort, Avon Longitudinal Study of Parents and Children [ALSPAC]).</p><p><strong>Methods: </strong>Correlation between DHEAS and pubertal measurements was assessed by Spearman's correlation. DHEAS association with methylation at individual CpGs or regions was evaluated by linear regression, and nearby genes examined by enrichment analysis and intersection with known puberty-related genes.</p><p><strong>Results: </strong>Boys and girls with higher childhood DHEAS concentrations had more advanced pubic hair growth throughout puberty; girls also had advanced breast development, earlier menarche, and longer menstrual cycles. DHEAS concentration was associated with methylation at individual CpGs near several puberty-related genes. In boys, 14 genes near CpG islands with DHEAS-associated methylation were detected, and in girls, there were 9 which included LHCGR and SRD5A2; FGFR1 and FTO were detected in both sexes.</p><p><strong>Conclusions: </strong>The association between DHEAS and pubertal development, as reported previously, suggests a physiological connection. Our novel findings showing that DHEAS concentration correlates negatively and linearly with DNA methylation levels at regulatory regions of key puberty-related genes, provide a mechanism for such a functional relationship.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"623-635"},"PeriodicalIF":5.3,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817379","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}