Lynn Ogoniak, Sarah Sandmann, Julian Varghese, Michael J Ziller, Nina Neuhaus, Alexander Siegfried Busch
{"title":"Role of Genetics in the Age-Related Testosterone Decline in Men - A UK Biobank Study.","authors":"Lynn Ogoniak, Sarah Sandmann, Julian Varghese, Michael J Ziller, Nina Neuhaus, Alexander Siegfried Busch","doi":"10.1093/ejendo/lvaf143","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf143","url":null,"abstract":"<p><strong>Objective: </strong>Age-related decline in circulating testosterone levels in men varies significantly and is often linked to comorbidities such as type 2 diabetes, and cardiovascular disease (CVD). While the genetic basis of testosterone levels is well-studied, the role of genetics in age-related testosterone decline remains unclear. This study aims to investigate the genetic contribution to age-related testosterone decline in men and its association with comorbidities.</p><p><strong>Design: </strong>A longitudinal, population-based study in 6,354 men including consecutive testosterone (T), bioavailable testosterone (BAT), and sex hormone-binding globulin (SHBG) measurements.</p><p><strong>Methods: </strong>We assessed the association of longitudinal serum biomarker changes with changes in disease prevalences and a polygenic score (PGS) for BAT developed in 183,909 UK Biobank participants.</p><p><strong>Results: </strong>In the follow-up cohort (mean age: 58.2 years; mean follow-up: 4.3 years), baseline levels of BAT, T, and SHBG were each negatively associated with their respective relative changes at follow-up (all p<0.001). A PGS for BAT, strongly associated with baseline levels (p=2.2x10-16, R²=0.16), was not associated with BAT decline over time. Genome-wide analysis of BAT change identified no significant genetic loci. Instead, the BAT decline was associated with prevalence of several comorbidities including cancers and CVD (p=0.007 and 0.012, respectively).</p><p><strong>Conclusions: </strong>Non-genetic factors are strongly associated with age-related BAT decline, whereas genetic predisposition may have a limited role. However, this does not rule out a potential genetic contribution. Our findings offer insight into the relationship between comorbidities and hormonal changes, supporting further research into their roles in testosterone decline and related health risks in aging men.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648869","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}
Laura Rotolo, Greta Galante, Kimberly Coscia, Valentina Bissi, Lorenzo Tucci, Marco Mezzullo, Alessandra Gambineri, Valentina Vicennati, Guido Zavatta, Uberto Pagotto, Guido Di Dalmazi, Flaminia Fanelli
{"title":"Impact of old and current immunoassays on the 1 mg overnight dexamethasone suppression test: comparison with LC-MS/MS.","authors":"Laura Rotolo, Greta Galante, Kimberly Coscia, Valentina Bissi, Lorenzo Tucci, Marco Mezzullo, Alessandra Gambineri, Valentina Vicennati, Guido Zavatta, Uberto Pagotto, Guido Di Dalmazi, Flaminia Fanelli","doi":"10.1093/ejendo/lvaf141","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf141","url":null,"abstract":"<p><strong>Objective: </strong>The influence of immunoassay performance in hypercortisolism and dexamethasone suppression test (DST) settings was scarcely investigated. We evaluated the effectiveness of two immunoassays in detecting hypercortisolism compared to recommended liquid chromatography-tandem mass spectrometry (LC-MS/MS), and compared immunoassay analytical performance in basal and post-DST conditions.</p><p><strong>Methods: </strong>We measured cortisol in post-DST sera of patients with suspected hypercortisolism or adrenal incidentalomas by Elecsys gen I (n=260), and by Access (n=217). All samples were also measured by a validated LC-MS/MS method. We estimated hypercortisolism rate according to the established 50 nmol/L cut-off, and generated immunoassay-specific cut-offs providing >95% sensitivity and >80% specificity. Finally, we compared cortisol measurements in basal and post-DST samples.</p><p><strong>Results: </strong>Using the 50 nmol/L cut-off, both immunoassays detected lower rates of hypercortisolism compared with LC-MS/MS, particularly in patients with adrenal adenomas (P<0.050). Elecsys gen I and Access determined 6.9% and 6.4% possible false negatives, respectively. Elecsys gen I also caused 3.8% possible false positives. Optimal cut-off was 41 nmol/L for Elecsys gen I (sensitivity: 97.7%; specificity: 80.8%), and 33 nmol/L for Access (sensitivity: 97.5%; specificity: 78.3%). In basal and post-DST samples, Elecsys gen I overestimated by 32.5% and 6.1%, whereas Access underestimated by -4.7% and -5.9% compared to LC-MS/MS cortisol measurements, respectively. Sex differences in method deviations were noted.</p><p><strong>Conclusions: </strong>Both immunoassays demonstrated remarkable underdetection of hypercortisolism, suggesting the application of a method-specific cut-off. Immunoassay performance may not be uniform in basal and post-DST conditions and should be purposely examined. Accurate LC-MS/MS methods should be preferred in hypercortisolism settings.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636525","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":"Multimodal Advanced Imaging for Precision Medicine in Pituitary Tumors.","authors":"Felicia Hanzu, Josep Puig, Paloma Puyalto, Manel Puig-Domingo","doi":"10.1093/ejendo/lvaf144","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf144","url":null,"abstract":"<p><p>Advances in imaging technologies are revolutionizing the understanding and management of pituitary diseases including pituitary adenomas, hypopituitarism, and neuroendocrine disorders. This review highlights state-of-the-art bioimaging tools, including magnetic resonance imaging, spectroscopy, functional positron emission tomography, and radiomics, and emphasizes their roles in diagnosis, characterization, treatment planning, and prognostication in precision medicine of pituitary tumors. We discuss technological advancements, integration with omics data, and future research directions for enhancing diagnostic accuracy and therapeutic outcomes. This comprehensive review underscores the pivotal role of advanced bioimaging tools in enhancing diagnostic accuracy, individualized treatment planning, and prognostic assessment, ultimately paving the way for a more personalized approach to managing pituitary tumors.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616887","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}
Issa Issa, Jakob Skov, Henrik Falhammar, Mikko Roos, Jonatan D Lindh, Buster Mannheimer
{"title":"The association of selective serotonin reuptake inhibitors and venlafaxine with profound hyponatremia.","authors":"Issa Issa, Jakob Skov, Henrik Falhammar, Mikko Roos, Jonatan D Lindh, Buster Mannheimer","doi":"10.1093/ejendo/lvaf140","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf140","url":null,"abstract":"<p><strong>Background: </strong>Profound hyponatremia (plasma sodium <125 mmol/L) due to serotonergic antidepressants has mostly been addressed in small epidemiological studies. Given the potentially severe consequences of profound hyponatremia, there is a clear need to re-evaluate this risk in a larger cohort.</p><p><strong>Aims: </strong>The aim of the study was to investigate the association of newly initiated selective serotonin reuptake inhibitors (SSRIs) or venlafaxine with profound hyponatremia.</p><p><strong>Material and methods: </strong>The study was based on the Stockholm Sodium Cohort including health data on 1,632,249 individuals. First-time users of SSRI/venlafaxine who initiated treatment between 2007 and 2017 were included. We assessed the individual's plasma sodium concentration in relation to the drug usage with the individual as its own control.</p><p><strong>Results: </strong>In total, 234,217 first-time users were included, and 3,999 individuals developed profound hyponatremia at least once. After initiation of SSRI/venlafaxine (baseline) the incidences of profound hyponatremia among individuals 65-79 and ≥80 years were 3% and 4%, respectively. Among individuals ≥80 years, the incidence was 6.5% for women and 3.4% for men. The adjusted odds ratio (aOR) for profound hyponatremia was 4.29 (95%CI 3.34-5.52) the first three months after SSRIs/venlafaxine initiation. After one year, the aOR was 1.30 (95%CI 0.97-1.75). During the first two weeks, the aOR was 10.06 (95%CI 5.97-17.00).</p><p><strong>Conclusions: </strong>There was a strong association between newly initiated SSRI/venlafaxine and profound hyponatremia. The risk increased with age and female sex affecting 1 in 15 women ≥80 years. Consequently, heightened vigilance for hyponatremia is recommended following SSRI/venlafaxine initiation, particularly in elderly patients.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590763","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}
A R Kruijsen, J M Wit, K de Groote, L D Punt, A S P van Trotsenburg, K J Pijnenburg-Kleizen, G Bocca, L Berkenbosch, P A van Setten, H L Claahsen-van der Grinten, D C M van der Kaay, N Schott, V van Tellingen, E G A H van Mil, J C van der Heyden, A E Brandsma, Y Hendriks, M Losekoot, H A van Duyvenvoorde, A C S Hokken-Koelega, J S Renes, C de Bruin, S D Joustra
{"title":"Growth hormone treatment adjusted for growth hormone sensitivity in idiopathic short stature.","authors":"A R Kruijsen, J M Wit, K de Groote, L D Punt, A S P van Trotsenburg, K J Pijnenburg-Kleizen, G Bocca, L Berkenbosch, P A van Setten, H L Claahsen-van der Grinten, D C M van der Kaay, N Schott, V van Tellingen, E G A H van Mil, J C van der Heyden, A E Brandsma, Y Hendriks, M Losekoot, H A van Duyvenvoorde, A C S Hokken-Koelega, J S Renes, C de Bruin, S D Joustra","doi":"10.1093/ejendo/lvaf137","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf137","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the long-term growth responses to recombinant human growth hormone (rhGH) in children with idiopathic short stature (ISS), decreased IGF-1 levels and a normal stimulated GH peak, after assessing their GH sensitivity using the IGF-1 generation test (IGFGT).</p><p><strong>Design: </strong>Retrospective descriptive case series.</p><p><strong>Methods: </strong>129 children with height <-2.5 SDS, IGF-1 <-2.0 SDS on two occasions, and peak GH >10 µg/L, underwent an IGFGT to be categorized into normal (neurosecretory dysfunction), intermediate, or low GH sensitivity. The first group was treated with a rhGH substitution dose (0.025-0.035 mg/kg) and the others with a higher dose (0.035-0.050 mg/kg). Patients were followed for at least one year, with 58 patients reaching near-adult height (NAH). Prepubertal and pubertal patients were analysed separately.</p><p><strong>Results: </strong>During the first year of treatment in prepubertal patients, height increased by 0.8±0.4 SDS, height velocity by 4.0±2.1 cm/year, and predicted adult height (PAH) by 0.6±0.7 SDS. At NAH, average height was -1.0±1.0 SDS, which is 2.1±0.8 SDS higher than height at start, 1.5±0.8 SDS higher than PAH at start, and 0.3±0.9 SDS below target height. No group differences were observed. Using the rhGH treatment prediction models from the KIGS database, patients performed better than expected for ISS, and similar to patients with idiopathic isolated GH deficiency.</p><p><strong>Conclusion: </strong>Children with ISS, decreased IGF-1 levels and a normal stimulated GH peak show a good response to rhGH treatment. The IGFGT is a useful tool for selecting this subgroup from ISS patients and optimizing rhGH dose.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575100","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}
Fabio Bioletto, Caroline Bogeat, Maxime Barat, Nesrine Benanteur, Laurence Guignat, Mirella Hage, Cyril Garcia, Valentin Calugaru, Julian Jacob, Jennifer Arrondeau, Lionel Groussin, Xavier Bertagna, Jérôme Bertherat, Chiara Villa, Anne Jouinot, Bertrand Baussart, Guillaume Assié
{"title":"Progression of potentially aggressive PitNETs after radiotherapy: risk factors, management, and outcomes.","authors":"Fabio Bioletto, Caroline Bogeat, Maxime Barat, Nesrine Benanteur, Laurence Guignat, Mirella Hage, Cyril Garcia, Valentin Calugaru, Julian Jacob, Jennifer Arrondeau, Lionel Groussin, Xavier Bertagna, Jérôme Bertherat, Chiara Villa, Anne Jouinot, Bertrand Baussart, Guillaume Assié","doi":"10.1093/ejendo/lvaf136","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf136","url":null,"abstract":"<p><strong>Objective: </strong>Radiotherapy plays a relevant role in uncontrolled pituitary neuroendocrine tumors (PitNETs). Radiotherapy controls tumor progression in most cases, but not always. Prognostic factors for tumor progression after radiotherapy remain poorly defined. The aim was to evaluate tumor progression after radiotherapy, to identify risk factors, and to report management and outcomes in a cohort of PitNETs with uncontrolled progression.</p><p><strong>Design: </strong>Retrospective, single-center, observational study.</p><p><strong>Methods: </strong>In total, 123 consecutive patients who underwent radiotherapy for PitNETs and were followed at Cochin Hospital between 2000 and 2022 were included. Indication for radiotherapy was uncontrolled tumor progression (80%), adjuvant (9%) or uncontrolled secretion (11%). Median follow-up after radiotherapy was 10.0 years.</p><p><strong>Results: </strong>Tumor progression after radiotherapy was observed in 28/123(23%) patients. Higher risk of progression was associated with lactotroph and corticotroph tumor types (HR[95%CI] 12.0[1.2-117.1] and 9.3[1.3-69.6], respectively), male sex (3.7[1.6-8.4]), and necrotic-hemorrhagic changes before radiotherapy on MRI (3.1[1.1-8.4]). Surgery, temozolomide and re-irradiation were the most frequent treatments for the management of patients with tumor progression after radiotherapy, used in 18/28(64%), 16/28(57%) and 8/28(29%) cases, respectively. The most common complication of radiotherapy was the new onset of pituitary deficits, observed in 41% of cases; other complications, including radiation-induced neuroinflammation, cerebrovascular events, and second brain tumors, were rare. Three patients developed metastases, and 6 patients died because of tumor progression.</p><p><strong>Conclusions: </strong>Lactotroph and corticotroph PitNETs, in male patients, and/or with necrotic-hemorrhagic changes are at higher risk of progression after radiotherapy. Patients with progression after radiotherapy require additional heavy treatments with variable outcome.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559546","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}
Kristina Isand, Riccardo Pofi, Oliver Haermson, Melissa Vergis, Harishanthi Mahendran, John Ayuk, John Wass, Parag Yajnik, Karin Bradley, Niki Karavitaki, Aparna Pal
{"title":"Venous thromboembolism in patients with pituitary adenoma: UK multicentre cohort study.","authors":"Kristina Isand, Riccardo Pofi, Oliver Haermson, Melissa Vergis, Harishanthi Mahendran, John Ayuk, John Wass, Parag Yajnik, Karin Bradley, Niki Karavitaki, Aparna Pal","doi":"10.1093/ejendo/lvaf139","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf139","url":null,"abstract":"<p><strong>Objective: </strong>To assess risk of venous thromboembolism (VTE) in patients with Cushing's disease (CD) compared to acromegaly and non-functioning pituitary adenomas (NFPA) and to investigate the timing and risk factors for VTE.</p><p><strong>Design: </strong>Retrospective, observational cohort study.</p><p><strong>Methods: </strong>Patients diagnosed with acromegaly, NFPA, or CD across three UK centres between 2010 and 2021 were included. Chi-square and Cox regression were performed to compare VTE cumulative incidence and examine associations with clinical factors.</p><p><strong>Results: </strong>Among 827 patients (107 CD, 502 NFPA, 218 acromegaly) the cumulative incidence of VTE was 11.2% in CD, 0.4% in NFPA, and 2.7% in acromegaly. Follow-up time was similar across diagnostic groups (median ∼13.3-13.5 years, p = 0.41), allowing valid comparison of VTE incidence and Cox regression modelling. Patients with CD had significantly higher VTE risk compared to with NFPA (odds ratio (OR) 21.05, p < 0.001) and acromegaly (OR 4.48, p = 0.002). Cox regression showed that CD diagnosis (hazard ratio (HR) 46.87, p < 0.001) and history of diabetes or impaired glucose tolerance (HR 3.48, p = 0.008) were significantly associated with VTE.In patients with CD, there were 12 VTE's recorded, with most (8/12) occurring within one year of CD diagnosis. Notably, four VTEs occurred within 45 days post-transsphenoidal surgery (TSS).</p><p><strong>Conclusion: </strong>Patients with CD exhibit a significantly elevated risk of VTE compared to those with acromegaly or NFPA, with diabetes mellitus independently associated with this risk. In CD, VTEs were more frequently diagnosed around the time of diagnosis and during the perioperative period.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559547","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":"Phase 1 study and population PK/PD modeling of long-acting growth hormone, GB08, to guide pediatric dosing.","authors":"Hengxin Peng, Wei Shang, Yanqing Lin, Jiajun Xu, Jiang Zhu, Wen He, Suofu Qin","doi":"10.1093/ejendo/lvaf131","DOIUrl":"10.1093/ejendo/lvaf131","url":null,"abstract":"<p><strong>Objective: </strong>Growth hormone deficiency (GHD) requires long-term treatment, but daily injections and adverse effects of current therapies often pose adherence challenges in children. GB08, a novel Fc-GH, leverages the extended half-life of Fc-fusion proteins to reduce injection frequency with potential for improved safety. This study evaluates the safety, immunogenicity, pharmacokinetics, and pharmacodynamics profiles of GB08 in healthy adults. The findings, along with population PK/PD modeling, will guide dosing strategies for a Phase 2 trial in pediatric GHD patients.</p><p><strong>Design: </strong>The study consisted of 2 parts: a randomized, double-blind, placebo-controlled single ascending dose trial and a randomized, open-label, parallel-group positive control trial.</p><p><strong>Methods: </strong>Subjects received a single dose of GB08 (0.16-2.4 mg/kg), 0.2 mg/kg of Jintrolong, or 7 daily doses of Norditropin (0.035 mg/kg/day). Evaluations included adverse events (AEs), immunogenicity, pharmacokinetics, and pharmacodynamics.</p><p><strong>Results: </strong>GB08 demonstrated a favorable safety profile with low immunogenicity, no serious AEs reported, and all AEs were mild to moderate. Pharmacokinetics and pharmacodynamics revealed dose-dependent increases, with GB08's half-life ranging from 81.7 to 110.0 h, supporting its potential for once-weekly injection. PK/PD modeling identified an optimal adult dose of 0.7 mg/kg. Further allometric scaling of adult PK data to develop a pediatric PK model suggested optimal pediatric dose of 0.8 mg/kg, balancing efficacy and safety profiles.</p><p><strong>Conclusion: </strong>GB08 provides notable advantages over traditional therapies, like short-acting GH, by enhancing treatment adherence and offering a potentially safer alternative. The findings from this study will guide dosing strategies for Phase 2 trial in children with GHD.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"117-128"},"PeriodicalIF":5.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505224","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}
Masanori Murakami, Mitsuhide Naruse, Hiroki Kobayashi, Mirko Parasiliti-Caprino, Fabio Bioletto, Denise Brüdgam, Isabel Stüfchen, Martin Reincke, Matthieu St-Jean, Ivana Kraljevic, Darko Kastelan, Pasi I Nevalainen, Marta Araujo-Castro, Norlela Sukor, Michiel F Nijhoff, Joanna Matrozova, Oskar Ragnarsson, Zulfiya Shafigullina, Niina Matikainen, Athina Markou, George Piaditis, Shoichiro Izawa, Takuyuki Katabami, Takamasa Ichijo, Akiyo Tanabe, Mika Tsuiki, Miki Kakutani, Norio Wada, Seizaburo Masuda, Alessandra Violet Bacca, Felix Beuschlein, Giuseppe Maiolino, Henrik Falhammar, Marianne A Grytaas, Kristian Løvås, Madson Q Almeida, Raluca Maria Furnica, Troy Puar, Piotr Kmieć, Stefano Masi, Isabelle Bourdeau, Laurence Amar, Michael Conall Dennedy, Francesco Fallo, Jaap Deinum, Sam O'Toole, Tetsuya Yamada, Marcus Quinkler, André Lacroix, Tomaz Kocjan
{"title":"Expert Consensus on the Primary Aldosteronism Severity Classification and its strategic application in indicating adrenal venous sampling.","authors":"Masanori Murakami, Mitsuhide Naruse, Hiroki Kobayashi, Mirko Parasiliti-Caprino, Fabio Bioletto, Denise Brüdgam, Isabel Stüfchen, Martin Reincke, Matthieu St-Jean, Ivana Kraljevic, Darko Kastelan, Pasi I Nevalainen, Marta Araujo-Castro, Norlela Sukor, Michiel F Nijhoff, Joanna Matrozova, Oskar Ragnarsson, Zulfiya Shafigullina, Niina Matikainen, Athina Markou, George Piaditis, Shoichiro Izawa, Takuyuki Katabami, Takamasa Ichijo, Akiyo Tanabe, Mika Tsuiki, Miki Kakutani, Norio Wada, Seizaburo Masuda, Alessandra Violet Bacca, Felix Beuschlein, Giuseppe Maiolino, Henrik Falhammar, Marianne A Grytaas, Kristian Løvås, Madson Q Almeida, Raluca Maria Furnica, Troy Puar, Piotr Kmieć, Stefano Masi, Isabelle Bourdeau, Laurence Amar, Michael Conall Dennedy, Francesco Fallo, Jaap Deinum, Sam O'Toole, Tetsuya Yamada, Marcus Quinkler, André Lacroix, Tomaz Kocjan","doi":"10.1093/ejendo/lvaf117","DOIUrl":"10.1093/ejendo/lvaf117","url":null,"abstract":"<p><strong>Objective: </strong>Severity classifications are essential for many diseases to prioritize patient management tasks such as diagnosis, treatment, and follow-up. Primary aldosteronism (PA), a common cause of secondary hypertension, lacks a standardized severity scale despite generally requiring invasive diagnostics like adrenal venous sampling (AVS). This study aimed to develop a global expert consensus-based classification for PA severity to improve clinical decision-making.</p><p><strong>Methods: </strong>A panel of 45 international experts from 40 centers across four continents used the Delphi method to create a consensus severity classification for PA. This classification was then applied retrospectively to 2593 PA patients from 26 centers to assess its association with the disease subtype.</p><p><strong>Results: </strong>After four rounds, the Primary Aldosteronism Severity Classification (PASC), which integrates biochemical and clinical parameters including serum potassium, blood pressure, and basal plasma aldosterone concentration, was established. Primary Aldosteronism Severity Classification classifies PA into mild (3 and 4 points), moderate (5-7 points), and severe (8 and 9 points). Among the cohort from 26 centers, 13.9%, 63.0%, and 23.1% were classified as mild, moderate, and severe, respectively, aligning with lateralized subtype prevalence rates of 14.7%, 44.6%, and 72.6%.</p><p><strong>Conclusion: </strong>Primary Aldosteronism Severity Classification is a newly developed simplified, semi-quantitative classification of PA severity. The correlation between PASC and lateralized PA subtype supports its potential to provide graded recommendations of AVS prior to surgical indication in each patient.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"85-96"},"PeriodicalIF":5.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247070","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}
Wiebke Arlt, Aude Brac de la Perrière, Angelica L Hirschberg, Deborah P Merke, John D C Newell-Price, Alessandro Prete, D Aled Rees, Nicole Reisch, Philippe A Touraine, Hanna Bendfeldt, John Porter, Helen Coope, Richard J M Ross
{"title":"Long-term outcomes in patients with congenital adrenal hyperplasia treated with hydrocortisone modified-release hard capsules.","authors":"Wiebke Arlt, Aude Brac de la Perrière, Angelica L Hirschberg, Deborah P Merke, John D C Newell-Price, Alessandro Prete, D Aled Rees, Nicole Reisch, Philippe A Touraine, Hanna Bendfeldt, John Porter, Helen Coope, Richard J M Ross","doi":"10.1093/ejendo/lvaf130","DOIUrl":"10.1093/ejendo/lvaf130","url":null,"abstract":"<p><strong>Background: </strong>Hydrocortisone modified-release hard capsules (MRHC, development name Chronocort) replace the physiological overnight cortisol rise and improve the biochemical control of congenital adrenal hyperplasia (CAH).</p><p><strong>Aim: </strong>This study aims to evaluate long-term safety, tolerability, and efficacy of MRHC.</p><p><strong>Methods: </strong>This is an open-label follow-on study.</p><p><strong>Results: </strong>Ninety-one patients with classic CAH, mean age 37 years, 68% female, 32% male, entered the study and 22 discontinued. Median treatment duration was 4 years (range 0.2-5.8). Median hydrocortisone dose at study entry was 30 mg/day and reduced to 20 mg/day after 24 weeks and stayed stable thereafter until 48 months (P < .0001). Disease control improved on MRHC for the steroid disease markers serum 17-hydroxyprogesterone (17OHP) (P < .03) and androstenedione (A4) (P < .002). After 4 years, the majority of patients had a 17OHP < 4-fold upper limit of normal (ULN) (71%) and an A4 <ULN (90%). Measurement of 17OHP and A4 at 09:00 h and 13:00 h gave similar results. Of the 37 women < 50 years of age who were not on contraceptives over the whole study period, 5 became pregnant (13.5%). Of the men, 13.8% (4/29) had a partner pregnancy. Seven patients had an adrenal crisis with 1 patient reporting 8 of these giving an incidence of 3.9 crises per 100 patient years.</p><p><strong>Conclusions: </strong>Modified-release hard capsule treatment resulted in hydrocortisone dose reduction followed by a stable dose with improved biochemical control associated with fertility. Biochemical control could be reliably monitored by a single blood sample taken between 09:00 and 13:00 h. The incidence of adrenal crises was below that reported previously in patients with CAH.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"76-84"},"PeriodicalIF":5.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505221","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}