European Journal of Endocrinology最新文献

{"title":"Estimated global prevalence of genetic carriers of hereditary pheochromocytoma-paraganglioma syndrome in a large multiethnic genomic database.","authors":"Nipith Charoenngam, Taweesak Wannachalee","doi":"10.1093/ejendo/lvaf191","DOIUrl":"10.1093/ejendo/lvaf191","url":null,"abstract":"<p><strong>Objectives: </strong>To estimate the global prevalence of genetic carriers of pheochromocytoma-paraganglioma syndromes (PPGLs) in a large multiethnic genomic database.</p><p><strong>Methods: </strong>We analyzed sequencing data from 807 162 unrelated individuals in the gnomAD v4.1 database, representing a global population of diverse ethnic ancestries. Eleven PPGLs-associated genes were examined: FH, NF1, RET, SDHA, SDHAF2, SDHB, SDHC, SDHD, TMEM127, VHL, and MAX. Pathogenic or likely pathogenic variants (P/LP) were identified from ClinVar, while additional predicted deleterious variants were included based on loss-of-function annotations and splice prediction in silico tools. Prevalence estimates of genetic carriers were calculated by combining allele frequencies of qualifying variants.</p><p><strong>Results: </strong>The prevalence of SDHA carriers was the highest when aggregating allele frequencies of both ClinVar P/LP and predicted deleterious variants (158.83 per 100 000), followed by NF1 (93.66 per 100 000) and FH (72.23 per 100 000), while VHL and MAX had the lowest prevalence. Substantial variation was observed across ancestries, with certain variants enriched in specific populations (eg, SDHC p.Tyr126Cys in non-Finnish Europeans; FH c.556-4A > G in East Asians). Carriers of SDHB, SDHC, and TMEM127 ClinVar P/LP or predicted deleterious variants were absent in the Middle Eastern group; SDHAF2 and SDHC were absent in the Ashkenazi Jewish group; and SDHAF2 and TMEM127 were absent in the Finnish group. Predicted deleterious variants significantly increased carrier estimates for SDHAF2, SDHD, and TMEM127.</p><p><strong>Conclusion: </strong>Our study highlights the variability in PPGL-associated mutation carrier prevalence across genes and ancestries. The findings underscore potential disparities in genetic risk that may not have been fully captured by clinical cohorts.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"412-420"},"PeriodicalIF":5.2,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091365","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":"A preliminary model to tailor osilodrostat in patients with Adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome.","authors":"Cecilia Piazzola, Frederic Castinetti, Katharina von Fabeck, Nicolas Simon","doi":"10.1093/ejendo/lvaf185","DOIUrl":"10.1093/ejendo/lvaf185","url":null,"abstract":"<p><p>Over the past 10 years, osilodrostat has become one of the most commonly used steroidogenesis inhibitors in patients with Cushing's syndrome. The starting dose is usually determined based on the product characteristics, the prescriber's experience, and cortisol levels. However, no study has attempted to determine whether there was a dose-response relationship between osilodrostat and cortisol reduction. In this study, we developed a preliminary kinetic-pharmacodynamic model to tailor osilodrostat in patients with Adrenocorticotropin hormone (ACTH)-dependent Cushing's syndrome. We first analyzed the decrease in cortisol 48 hours after initiation or dose change of osilodrostat in 18 patients. Simulations were then performed for different doses of osilodrostat to evaluate the variation in cortisol concentrations. Our results report the first dose-response relationship between osilodrostat dose and cortisol levels, which should be helpful in identifying the optimal dosing regimen in patients with Cushing's syndrome and in individualizing treatment to approximate a nychthemeral rhythm.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"K11-K15"},"PeriodicalIF":5.2,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091354","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":"Use of skeletal muscle fiber composition to assess relationship between amino acid metabolism and insulin sensitivity.","authors":"Tova Eurén Magnusson, Sarah J Blackwood, Dominik Tischer, Timotej Strmeň, Marjan Pontén, Sebastian Edman, Oscar Horwath, William Apró, Marcus Moberg, Elin Chorell, Abram Katz","doi":"10.1093/ejendo/lvaf195","DOIUrl":"10.1093/ejendo/lvaf195","url":null,"abstract":"<p><strong>Objectives: </strong>Here we use skeletal muscle fiber composition to investigate whether defects in amino acid metabolism are involved in the early development of IR in healthy young individuals before the onset of clinical manifestations.</p><p><strong>Design: </strong>Two groups consisting of healthy young men and women, insulin-sensitive and insulin-resistant, were studied using a cross-sectional design.</p><p><strong>Methods: </strong>Biopsies were obtained from the vastus lateralis muscle, and an intravenous glucose tolerance test was performed. Plasma and muscle tissue were analyzed by metabolomics.</p><p><strong>Results: </strong>Subjects in group 1 (n = 20; age 28 ± 5 years; body mass index 22.3 ± 2.7 kg/m2) had an expression of type I muscle fibers and whole-body insulin sensitivity of 58.8% ± 5.7% and 1.8 ± 0.7 units, respectively. Subjects in group 2 (n = 16; age 25 ± 6 years; body mass index 22.6 ± 3.0 kg/m2) had an expression of type I muscle fibers and whole-body insulin sensitivity, respectively, of 29.8% ± 6.6% and 0.8 ± 0.3 units (P < .001 vs group 1 for both). Anserine and β-alanine contents in muscle were significantly higher and taurine lower in group 2 vs 1, consistent with the differences in muscle fiber composition between groups. Taurine correlated well with insulin sensitivity and expression of type I muscle fibers (r = 0.63; P < .001 for both). In contrast, there were no significant differences in plasma or tissue contents of glutamine, arginine, or branched-chain amino acids between groups.</p><p><strong>Conclusions: </strong>These data demonstrate that the early development of IR is not a consequence of defects in amino acid metabolism. Rather, defects in amino acid metabolism in diseased states are more likely a consequence of IR.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"553-563"},"PeriodicalIF":5.2,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091426","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":"Health-related quality of life in a cohort of 1070 patients with hypoparathyroidism.","authors":"Heide Siggelkow, Tamara Vokes, Neil Gittoes, Olulade Ayodele, Maria Luisa Brandi, Felicia Castriota, Michael A Levine, Carolyn Schaeffer Koziol, Lars Rejnmark, Aliya A Khan, Pinggao Zhang, Claudio Marelli, John Germak, Michael Mannstadt","doi":"10.1093/ejendo/lvaf169","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf169","url":null,"abstract":"<p><strong>Objective: </strong>To describe clinical and biochemical characteristics, including health-related quality of life (HRQoL), in patients with chronic hypoparathyroidism (cHypoPT) who were receiving conventional therapy (calcium and active vitamin D), and to compare baseline HRQoL between patients who subsequently received recombinant human parathyroid hormone (1-84) (rhPTH [1-84]) and those who did not.</p><p><strong>Design: </strong>Cross-sectional analysis of data recorded at enrollment (baseline) from patients with cHypoPT in the PARADIGHM registry before May 31, 2022.</p><p><strong>Methods: </strong>Eligible patients were aged ≥18 years and receiving conventional therapy at enrollment. Health-related quality of life was measured using the 36-Item Short-Form Health Survey version 2 (SF-36v2), Work Productivity and Activity Impairment Specific Health Problem (WPAI:SHP) questionnaire, and the Hypoparathyroidism Symptom Diary (HypoPT-SD).</p><p><strong>Results: </strong>Eligible patients (N = 1070) were mostly female (80.7%) and White (86.0%). Surgery was the most common cause of cHypoPT (82.2%). Mean serum albumin-adjusted calcium, phosphate, and calcium-phosphate product levels were within the target ranges. Mean (standard deviation [SD]) SF-36v2 physical and mental component scores were 46.3 (10.2) and 47.6 (11.5), respectively (normative scores: 50). Patients who went on to receive rhPTH (1-84) (n = 102) had significantly worse baseline HRQoL scores than patients in the conventional therapy group (n = 968) for all SF-36v2 and HypoPT-SD parameters and most WPAI parameters. There were no meaningful differences in biochemical parameters between the groups.</p><p><strong>Conclusions: </strong>Thirty-six-Item Short-Form Health Survey version 2 scores in patients with cHypoPT were lower than the normalized values reported previously for the US population. Patients who were subsequently prescribed rhPTH (1-84) had worse baseline HRQoL scores than those in the conventional therapy group.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"193 4","pages":"428-439"},"PeriodicalIF":5.2,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238092","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":"New routes to the neuroendocrine hypothalamus: the extracellular space.","authors":"Jean Charles Nicolas, Sabrina J P Huwart, Dorothea Ziemens, Oscar Freire-Agulleiro, Thomas Lee, Virginie Mattot, Carmelo Quarta","doi":"10.1093/ejendo/lvaf197","DOIUrl":"10.1093/ejendo/lvaf197","url":null,"abstract":"<p><p>The neuroendocrine hypothalamus integrates peripheral nutritional and hormonal cues to regulate essential physiological processes, including appetite, metabolism, and reproduction. While the mechanisms by which hormones traverse the blood-brain barrier to access the hypothalamic parenchyma are well characterized, how these signals subsequently diffuse and distribute within the brain's extracellular space and matrix remains poorly understood. Emerging evidence implicates specialized components of the extracellular matrix (ECM), such as perineuronal nets (PNNs), in modulating hormonal and nutrient bioavailability, as well as neuronal excitability and plasticity. In the hypothalamus, extracellular matrix components are highly dynamic and respond to nutritional and hormonal cues. In preclinical models of metabolic disorders involving the neuroendocrine system-such as obesity and type 2 diabetes-these components undergo maladaptive remodelling. This review discusses recent advances in our understanding of how the extracellular environment shapes neuroendocrine signaling in the hypothalamus and explores the broader implications for systemic hormonal regulation and neuroendocrine disease pathophysiology.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"R31-R42"},"PeriodicalIF":5.2,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091357","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":"Normal thyroid volume and goitre diagnosis on ultrasonography is population-sensitive.","authors":"Massimo Giusti","doi":"10.1093/ejendo/lvaf187","DOIUrl":"10.1093/ejendo/lvaf187","url":null,"abstract":"","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"L19-L20"},"PeriodicalIF":5.2,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091314","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":"The EndoCompass research roadmap: directions for the future of endocrine science.","authors":"Jérôme Bertherat, Anita Hokken-Koelega","doi":"10.1093/ejendo/lvaf142","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf142","url":null,"abstract":"","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"193 4","pages":"E1-E3"},"PeriodicalIF":5.2,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307249","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 the letter from Massimo Giusti.","authors":"Simone Kiel, Till Ittermann, Jean-François Chenot, Henry Völzke","doi":"10.1093/ejendo/lvaf188","DOIUrl":"10.1093/ejendo/lvaf188","url":null,"abstract":"","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"R1-R2"},"PeriodicalIF":5.2,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091491","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":"Adipose tissue signaling in aldosterone-producing adenomas: paracrine and endocrine effects.","authors":"Simon Kloock, Lisa Kagan, Christian Ziegler, Mugdha Srivastava, Anke Tönjes, Nada Rayes, Nicolas Schlegel, Niklas Geiger, Matthias Blüher, Martin Fassnacht, Ulrich Dischinger","doi":"10.1093/ejendo/lvaf190","DOIUrl":"10.1093/ejendo/lvaf190","url":null,"abstract":"<p><strong>Background: </strong>Primary aldosteronism increases the risk of cardiovascular and metabolic diseases, which might be influenced by different adipose tissue compartments. However, the interaction between the adrenal gland and different fat depots is not well understood and is the focus of this study.</p><p><strong>Methods: </strong>We analyzed subcutaneous adipose tissue (scAT) and periadrenal adipose tissue (paAT) from patients with aldosterone-producing adenomas (APAs; included scAT, n = 11; paAT, n = 18) and, as controls, nonfunctional adrenal adenomas (NFAs; included scAT, n = 7; paAT, n = 5). A subanalysis for KCNJ5-mutated APA (diagnosed through elevated 18-oxocortisol [18-oxoF] and 18-hydroxycortisol [18-OHF]) was conducted. RNA sequencing and immunohistochemistry of AT was performed (immunohistochemistry [IHC], only on scAT). Immunohistochemistry markers included adipokines (leptin, adiponectin) and transcription factors (eg, c-jun and calmodulin-dependent protein kinase II [CaMKII]).</p><p><strong>Results: </strong>RNA sequencing showed numerous significantly different expressed genes: APA vs NFA in scAT (68 up, 259 down), in paAT (16 up, 117 down), and in scAT vs paAT of APA patients (826 up, 1632 down). The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis highlighted downregulated inflammation-associated pathways in both APA fat depots, while steroid-related pathways were upregulated especially in paAT of patients with KCNJ5 mutation, suggesting paracrine effects of aldosterone. Lipolysis-associated pathways were upregulated in the scAT of APA patients. Immunohistochemistry showed increased expression of angiotensin-converting enzyme 2 (ACE2), CaMKII, and c-jun in scAT from APA patients.</p><p><strong>Conclusions: </strong>RNA sequencing identified significant gene expression differences in fat compartments of APA patients, implying endocrine and paracrine effects of APAs. These findings might partly explain cardiovascular consequences of primary aldosteronism and could lead to new diagnostic strategies, especially through accessible scAT.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"440-452"},"PeriodicalIF":5.2,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130150","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":"Serum steroid metabolome dynamics in infancy: a longitudinal cohort study of healthy infants.","authors":"Alexander Siegfried Busch, Marie Lindhardt Ljubicic, Emmie N Upners, Margit Bistrup Fischer, Casper P Hagen, Christa E Flück, Trine Holm Johannsen, Hanne Frederiksen, Anders Juul","doi":"10.1093/ejendo/lvaf193","DOIUrl":"10.1093/ejendo/lvaf193","url":null,"abstract":"<p><strong>Objective: </strong>The circulating steroid metabolome exhibits significant changes in both girls and boys during infancy, reflecting structural and functional changes in the adrenal cortex as well as the transient activation of the hypothalamic-pituitary-gonadal axis during minipuberty. However, longitudinal data characterizing these changes using liquid chromatography-tandem mass spectrometry (LC-MS/MS) remain limited. This study aimed to map the temporal dynamics of the serum steroid metabolome in healthy infants and establish sex- and age-specific reference curves.</p><p><strong>Design: </strong>Prospective, longitudinal birth cohort study (Copenhagen Minipuberty Study, 2016-2018; NCT02784184) including healthy, term, singleton newborns followed with repeated assessments during the first year of life.</p><p><strong>Methods: </strong>Serum levels of 16 steroid hormones were measured by LC-MS/MS in 88 girls and 101 boys in a total of 446 longitudinal samples. Age-specific reference values were modeled using Generalized Additive Models for Location, Scale and Shape (GAMLSS).</p><p><strong>Results: </strong>The steroid metabolome exhibited distinct patterns during infancy, characterized by increasing concentrations of cortisol and 11-deoxycorticosterone and decreasing levels eg, progesterone, 11-deoxycortisol, 17-hydroxyprogesterone, and androstenedione. These trends were largely independent of sex. Estimated activities of key steroidogenic enzymes did not differ significantly between sexes, except for sex steroid-related conversion; specifically, 17β-hydroxysteroid dehydrogenase activity was significantly higher in boys than girls (P < .001).</p><p><strong>Conclusions: </strong>These findings offer a comprehensive characterization of the serum steroid metabolome in healthy infants throughout the first year of life. The resulting age-specific reference curves may serve as valuable tools to support the clinical diagnosis and therapeutic monitoring of rare disorders of steroidogenesis. ClinicalTrials.gov ID: NCT01411527.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"403-411"},"PeriodicalIF":5.2,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091438","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}