European Journal of Endocrinology最新文献

{"title":"Osilodrostat dose impact on efficacy/safety in Cushing's disease: Large, pooled analysis of LINC 2, 3 and 4.","authors":"Maria Fleseriu, Rosario Pivonello, André Lacroix, Beverly M K Biller, Richard Feelders, Mônica Gadelha, Jérôme Bertherat, Zhanna Belaya, Andrea Piacentini, Alberto M Pedroncelli, John Newell-Price","doi":"10.1093/ejendo/lvaf207","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf207","url":null,"abstract":"<p><strong>Objectives: </strong>Evaluate how osilodrostat dose and baseline mean urinary free cortisol (mUFC) affect treatment outcomes and provide evidence-based guidance on personalized medical treatment for patients with Cushing's disease.</p><p><strong>Methods/design: </strong>Individual-patient data from the Phase II LINC 2 and Phase III LINC 3 and LINC 4 core and extension periods were pooled, excluding periods when patients received placebo (LINC 3 and LINC 4). Outcomes were evaluated in patients with available data across common time points.</p><p><strong>Results: </strong>229 patients were treated: starting osilodrostat dose 2mg twice daily, median average dose per patient 6.8mg/day for mean 113.7 weeks (standard deviation 73.1). mUFC control (not exceeding upper limit of normal) was achieved within 4-12 weeks in most patients and sustained throughout. Median time to first mUFC control was 35 days, longer with increasing baseline mUFC. Most common dose for first mUFC control was 4mg/day (33.2% of patients; median dose 10mg/day [range 2-60]). Adverse events (AEs) generally occurred more often during dose titration (baseline-week 12) than long-term treatment (week >12) but could occur at any time. AEs were manageable in most patients; n=37 (16.2%) discontinued because of AEs.</p><p><strong>Conclusions: </strong>In this analysis of the largest and longest prospective interventional studies of an adrenal steroidogenesis inhibitor to date, osilodrostat provided rapid and sustained mUFC control, with dose decreases possible over the long term. AE frequency generally decreased over time, with no relationship with osilodrostat dose. Personalized adjustment of osilodrostat dose is important to optimize outcomes for patients with Cushing's disease.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238070","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":"Latest Developments in Paget's Disease of Bone.","authors":"Stuart H Ralston","doi":"10.1093/ejendo/lvaf202","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf202","url":null,"abstract":"<p><p>Paget's disease of Bone is characterised by focal increases in osteoclastic bone resorption coupled to increased but disorganised bone formation. It is a relatively rare disease affecting up 1% of individuals in the UK, but many cases are not diagnosed clinically. The most common presentation is with musculoskeletal pain which in some cases is due to increased bone turnover, but which can also be due to complications such as bone deformity, nerve compression syndromes and osteoarthritis. Predisposition to Paget's disease is regulated by pathogenic variants in or close to genes that regulate osteoclast differentiation and function. The most important of these is SQSTM1 which encodes p62 - a signaling protein in the NFκB pathway. Environmental factors also influence susceptibility to PDB and disease severity, but the mechanisms are not well understood. Medical management is based on the use of bisphosphonates to supress the abnormal bone turnover and are indicated for the treatment of bone pain associated with the disease. Of the bisphosphonates currently available, intravenous zoledronic acid is the treatment of choice. The diagnosis can usually be made by typical features on x-ray and radionuclide bone scan. Genetic testing for pathogenic variants in the SQSTM1 gene in people with a family history of Paget's disease has been used to detect people with early asymptomatic disease and in these individuals, prophylactic treatment with zoledronic acid favourably affects disease progression.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211915","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 Regulation of Cardiac Repolarization: Early QTc Shortening after Testosterone in Healthy AFAB Adults.","authors":"Daniele Tienforti, Giovanni Terrana, Luca Spagnolo, Beatrice Fusco, Marco Giorgio Baroni, Arcangelo Barbonetti","doi":"10.1093/ejendo/lvaf201","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf201","url":null,"abstract":"<p><p>Testosterone modulates ventricular repolarization, yet the early time course of its effects in humans remains unclear. We conducted a prospective, single-centre study in ten healthy adults assigned female at birth initiating gender-affirming hormone therapy with daily transdermal testosterone gel. Standard 12-lead ECGs at baseline and 3 months showed no change in uncorrected QT, but significant QTc shortening by Bazett (-32 ms; p=0.002) and Fridericia (-14 ms; p=0.010) formulas, despite a concurrent heart rate reduction and with no association to changes in serum testosterone. These findings demonstrate rapid ventricular repolarization remodeling after testosterone initiation, with a magnitude comparable to the sex-based QTc gap. This study contributes to the characterization of early electrophysiologic adaptation to androgens in a standardized clinical model, and may inform cardiovascular monitoring strategies during abrupt hormonal transitions.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198755","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":"Advances in the Clinical Management of Parathyroid Disorders: Report from the 2024 Workshop by the ESE Educational Program on Parathyroid Disorders.","authors":"Luís Miguel Cardoso, Lars Rolighed, Karin Amrein, Stefan Pilz, Line Underbjerg, Mikkel Pretorius, Filomena Cetani, Alexandra Zahn, Martin Almquist, Ozer Makay, Claudio Marcocci, Lars Rejnmark, Heide Siggelkow, Elena Tsourdi, Peter Kamenický, Jens Bollerslev","doi":"10.1093/ejendo/lvaf204","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf204","url":null,"abstract":"<p><p>The present report from the ESE Educational Program on Parathyroid Disorders (PARAT Program) presents recent developments and novelties in the clinical care of parathyroid disorders in a question-and-answer format, based on a satellite workshop held in relation to the European Congress of Endocrinology in Stockholm, May 2024. The workshop focused on clinical aspects of three main themes: primary hyperparathyroidism (PHPT), chronic hypoparathyroidism (HypoPT) in adults, and parathyroid disorders in pregnancy, with an emphasis on advances since the 2022 PARAT consensus report. The first section focuses on the long-term complications - including fractures, renal impairment, mental health, and quality of life - in patients with asymptomatic or mild forms of PHPT and on treatment strategies for syndromic PHPT (multiple endocrine neoplasia 1-4). In the latter, we explore appropriate surgical and non-surgical approaches, imaging techniques for gland localization, and preservation strategies in cases of multiglandular involvement. The second section addresses transient and partial forms of HypoPT in comparison to chronic and complete parathyroid hormone deficiency. It highlights the potential skeletal consequences of chronic HypoPT, the underlying etiologies, and discusses treatment modifications in light of the evolving therapeutic landscape. The final section, dedicated to the specific considerations of parathyroid disorders during pregnancy and lactation, focuses on pregnancy planning in patients with hereditary syndromic forms of PHPT, the differentiation between parathyroid-related and unrelated causes of hypercalcemia, and the associated risks for both mother and fetus. Additionally, it addresses the practical aspects of managing pregnant women with HypoPT, aiming to provide practical guidance for clinicians. Clinical vignettes featuring 3 cases illustrate common clinical situations.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205951","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 Osteoporotic Fracture Risk in Postsurgical Hypoparathyroidism A Critical Appraisal.","authors":"Min Li, Yingchun Zhou, Dongdong Zhang, Ming Cai","doi":"10.1093/ejendo/lvaf205","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf205","url":null,"abstract":"","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206013","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":"Increased mortality in primary adrenal insufficiency: a systematic review and meta-analysis.","authors":"Konstantinos Dalakas, Francesca Allosso, Christian Basile, Ragnhildur Bergthorsdottir, Dimitrios Chantzichristos, Eva Hessman, Bright I Nwaru, Emanuele Bobbio, Daniela Pasquali, Gudmundur Johannsson, Daniela Esposito","doi":"10.1093/ejendo/lvaf186","DOIUrl":"10.1093/ejendo/lvaf186","url":null,"abstract":"<p><strong>Objective: </strong>Despite important advances in the management of primary adrenal insufficiency (PAI), prognosis in these patients remains poor. Data on mortality in PAI has not been entirely consistent, and to date, no systematic synthesis has been performed. The aim of this study was to conduct a systematic review and a meta-analysis to synthesize available evidence on mortality in adult patients with PAI including congenital adrenal hyperplasia (CAH).</p><p><strong>Design: </strong>This is a systematic review and meta-analysis.</p><p><strong>Methods: </strong>Medline, Cochrane CENTRAL, Web of Science, and Embase databases were searched for studies on mortality in PAI. The results were screened by 2 reviewers by titles and abstracts, and selected articles were subsequently reviewed in full text. Observational studies on mortality compared to a reference population were included.</p><p><strong>Results: </strong>Out of the 6238 reports identified, 9 reports were included in the systematic review, with a total population of 13 969 patients. Two of the 9 studies included overlapping population; therefore, only 7 studies were included in the meta-analysis (9876 patients). Four studies assessed mortality utilizing hazard ratio (HR) with a pooled HR of 2.51 (95% confidence interval [CI] 1.47-4.31, I2 = 86.1%); 3 studies used standardized mortality ratio (SMR) with a pooled SMR of 2.49 (95% CI 0.99-6.28, I2 = 97.9%). The main cause of death was cardiovascular disease. A sub-analysis of patients with CAH showed a pooled HR of 2.88 (95% CI 1.38-6.01, I2 = 90.3%), with the main cause of death being adrenal crisis.</p><p><strong>Conclusions: </strong>Mortality in patients with PAI was increased 2.5-fold compared to the reference population.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"S53-S60"},"PeriodicalIF":5.2,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085499","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":"Long-term antitumour effects of pasireotide in acromegaly.","authors":"Romy van der Groef, Sophie Veldhuijzen van Zanten, Denise van Beekveld, Eskeatnaf Mulugeta, Julie Refardt, Sebastian J C M M Neggers","doi":"10.1093/ejendo/lvaf194","DOIUrl":"10.1093/ejendo/lvaf194","url":null,"abstract":"<p><strong>Objective: </strong>Pasireotide long-acting release (LAR), a long-acting somatostatin receptor ligand, has shown potential antitumour activity in somatotroph pituitary tumours, as indicated by increased T2-signal intensity on magnetic resonance imaging (MRI). However, long-term follow-up data on its effects are limited. This study aimed to evaluate the long-term antitumour effects of pasireotide and its impact on clinical outcomes in patients with acromegaly.</p><p><strong>Design: </strong>The design is a retrospective cohort study.</p><p><strong>Methods: </strong>Patients from the previously published PAPE study were included. Over the course of 8 years, clinical outcomes, medication use, and tumour characteristics were assessed. T2-weighted MRI signals of tumours were analysed using grey matter as the reference region, and tumour volumes along with T2-intensity ratios (IRs) were calculated from all available scans.</p><p><strong>Results: </strong>Forty-four patients [57% male; median age 52 years (IQR 15)] were included. The median duration of pasireotide treatment was 31.0 months. From baseline to the 8-year follow-up, the median T2-IR increased from 1.03 to 1.56 (P < .001), indicating progressive cystic degeneration. Tumour volume significantly declined over time, with a median reduction from 1239 to 603 mm³ (P = .005). Importantly, 12 patients (27.3%) experienced a reduction in medical acromegaly treatment, without the need for surgery or radiotherapy due to decreasing insulin-like growth factor 1 (IGF1) levels.</p><p><strong>Conclusions: </strong>Pasireotide appears to induce durable cystic degeneration in somatotroph tumours, with evidence suggesting sustained antitumor effects that may extend beyond treatment discontinuation. These findings support its potential for a broader therapeutic role, warranting validation in future prospective studies.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"421-427"},"PeriodicalIF":5.2,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091351","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":"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":"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}