European Journal of Endocrinology最新文献

{"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}

{"title":"Assessing the clinical application of the PANOMEN 3 classification in a large cohort of pituitary tumors.","authors":"Prishila Fookeerah, Winny Varikatt, Meena Shingde, Mark A J Dexter, Sue Lynn Lau, Ann McCormack, Mark McLean","doi":"10.1093/ejendo/lvaf122","DOIUrl":"10.1093/ejendo/lvaf122","url":null,"abstract":"<p><strong>Objective: </strong>Pituitary tumors are a heterogeneous group of neoplasms exhibiting a wide range of clinical and histological features. There are currently no comprehensive clinically validated prognostic tools to guide management of all tumor types before and after surgery. Recently, the PANOMEN 3 classification, incorporating risk factors for disease severity, was proposed as a potential grading system to assess prognosis. We aimed to evaluate the clinical utility and application of the new PANOMEN 3 classification.</p><p><strong>Design and methods: </strong>We conducted a retrospective study of 215 cases of pituitary tumors surgically resected at Westmead Hospital between 2011 and 2018. All tumors were histologically examined according to the 2022 WHO Classification of pituitary tumors. Preoperative and postoperative PANOMEN 3 grades were assigned, and recurrence analyses performed. Results were compared to the French clinicopathological classification.</p><p><strong>Results: </strong>Compared to PANOMEN 3 grade 0, risk of recurrence was highest for grade 3 (HR 10.99; 95% CI 1.14-106.11, P = .038), followed by grade 2 (HR 7.85; 95% CI 1.06-58.31, P = .044), but not significantly different for grade 1. Proportions of tumors needing further intervention was greater with higher PANOMEN 3 grades; interventions occurred earlier in high grade tumors. The French classification remained a significant predictor of recurrence when adjusted for PANOMEN 3 (P < .001), but PANOMEN 3 was not a strong predictor when adjusted for French classification (P = .374).</p><p><strong>Conclusions: </strong>In the postoperative setting, PANOMEN 3 classification is useful in prediction of recurrence and need for further therapy. However, it was a weaker tool for predicting recurrence than the French classification.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"56-64"},"PeriodicalIF":5.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511719","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":"Biallelic pathogenic variants in POMC can cause combined pituitary hormonal deficiency associated with severe obesity.","authors":"Géraldine Vitellius, Christine Poitou, Karine Clément, Jean Michel Petit, Blandine Gatta Cherifi, Souhila Amanzougarene, Mehdi Derhourhi, Alexandru Saveanu, Philippe Froguel, Amélie Bonnefond, Brigitte Delemer, Lauriane Le Collen","doi":"10.1093/ejendo/lvaf127","DOIUrl":"10.1093/ejendo/lvaf127","url":null,"abstract":"<p><strong>Objective: </strong>Biallelic variants in the pro-opiomelanocortin gene (POMC) can cause hypocortisolism, hypopigmentation, and early-onset obesity. Following the identification of 2 patients of combined pituitary hormone deficiency (CPHD), we investigated the prevalence of this association among carriers of rare pathogenic or likely pathogenic (P/LP) POMC variants.</p><p><strong>Design: </strong>This study is a case report and systematic literature review.</p><p><strong>Methods: </strong>Genetic analysis was conducted in a family with 2 cousins with childhood-onset obesity and CPHD. We assessed CPHD in carriers for biallelic pathogenic POMC variants using data from the literature and Human Gene Mutation Database. Clinical and biological data were collected, including pituitary axis involvement, obesity onset age, and pituitary imaging results.</p><p><strong>Results: </strong>The 2 cousins, compound heterozygous for POMC variants, developed CPHD following initial hypocortisolism, with subsequent hypothyroidism, growth hormone deficiency, and hypogonadism. Among 41 patients with biallelic POMC variants identified in the literature, 20 had rare homozygous/compound heterozygous P/LP POMC variants and detailed endocrine evaluations. Of these, 40% presented with CPHD, always associated with early-onset severe obesity and hypocortisolism. Growth hormone deficiency was the most frequent (75%), followed by thyrotropic and gonadotropic deficiencies (62.5%). No anomalies were revealed in pituitary imaging. Two patients recovered the gonadotropic axis after treatment with the MC4R agonist.</p><p><strong>Conclusion: </strong>These findings underscore the potential for CPHD to occur in carriers of biallelic pathogenic POMC variants. Sequencing the full POMC, including coding and regulatory regions, is crucial in CPHD cases, alongside evaluating all pituitary axes in neonatal hypocortisolism. Beyond weight regulation, setmelanotide may modulate hypothalamic-pituitary function, with implications for fertility.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"31-38"},"PeriodicalIF":5.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144289402","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":"Preexisting Diabetes and Pregnancy: An Endocrine Society and European Society of Endocrinology Joint Clinical Practice Guideline.","authors":"Jennifer A Wyckoff, Annunziata Lapolla, Bernadette D Asias-Dinh, Linda A Barbour, Florence M Brown, Patrick M Catalano, Rosa Corcoy, Gian Carlo Di Renzo, Nancy Drobycki, Alexandra Kautzky-Willer, M Hassan Murad, Melanie Stephenson-Gray, Adam G Tabák, Emily Weatherup, Chloe Zera, Naykky Singh-Ospina","doi":"10.1093/ejendo/lvaf116","DOIUrl":"10.1093/ejendo/lvaf116","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Preexisting diabetes (PDM) increases the risk of maternal and perinatal mortality and morbidity. Reduction of maternal hyperglycemia prior to and during pregnancy can reduce these risks. Despite compelling evidence that preconception care (PCC), which includes achieving strict glycemic goals, reduces the risk of congenital malformations and other adverse pregnancy outcomes, only a minority of individuals receive PCC. Suboptimal pregnancy outcomes demonstrated in real-world data highlight the need to further optimize prenatal glycemia. New evolving technology shows promise in helping to achieve that goal. Dysglycemia is not the only driver of poor pregnancy outcomes in PDM. The increasing impact of obesity on pregnancy outcomes underscores the importance of optimal nutrition and management of insulin sensitizing medications during prenatal care for PDM.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To provide recommendations for the care of individuals with PDM that lead to a reduction in maternal and neonatal adverse outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The Guideline Development Panel (GDP) composed of a multidisciplinary panel of clinical experts, along with experts in guideline methodology and systematic literature review, identified and prioritized 10 clinically relevant questions related to the care of individuals with diabetes before, during and after pregnancy. The GDP prioritized randomized controlled trials (RCTs) evaluating the effects of different interventions (eg, PCC, nutrition, treatment options, delivery) during the reproductive life cycle of individuals with diabetes, including type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Systematic reviews queried electronic databases for publications related to these 10 clinical questions. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and develop recommendations. The approach incorporated perspectives from 2 patient representatives and considered patient values, costs and resources required, acceptability and feasibility, and impact on health equity of the proposed recommendations.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In individuals with diabetes mellitus who have the possibility of becoming pregnant, we suggest asking a screening question about pregnancy intention at every reproductive, diabetes, and primary care visit. Screening for pregnancy intent is also suggested at urgent care/emergency room visits when clinically appropriate (2 | ⊕OOO). This was suggested based on indirect evidence demonstrating a strong association between PCC and both reduced glycated hemoglobin (HbA1c) at the first prenatal visit and congenital malformations.In individuals with diabetes mellitus who have the possibility of becoming pregnant, we suggest use of contraception when pregnancy is not desired (2 | ⊕⊕OO). This was suggested based on indirect evidence in women with diabetes, wh","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"193 1","pages":"G1-G48"},"PeriodicalIF":5.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625630","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":"Growth hormone treatment adjusted for growth hormone sensitivity in idiopathic short stature.","authors":"Anne R Kruijsen, Jan M Wit, Kirsten de Groote, Lauren D Punt, A S Paul van Trotsenburg, Karijn J Pijnenburg-Kleizen, Gianni Bocca, Lizanne Berkenbosch, Petra A van Setten, Hedi L Claahsen-van der Grinten, Daniëlle C M van der Kaay, Nina Schott, Vera van Tellingen, Edgar G A H van Mil, Josine C van der Heyden, Annelies E Brandsma, Yvonne Hendriks, Monique Losekoot, Hermine A van Duyvenvoorde, Anita C S Hokken-Koelega, Judith S Renes, Christiaan de Bruin, Sjoerd D Joustra","doi":"10.1093/ejendo/lvaf137","DOIUrl":"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 insulin-like growth factor I (IGF-1) levels, and a normal stimulated GH peak, after assessing their growth hormone (GH) sensitivity using the IGF-1 generation test (IGFGT).</p><p><strong>Design: </strong>This was a retrospective descriptive case series.</p><p><strong>Methods: </strong>One hundred and twenty-nine children with height < -2.5 standard deviation score (SDS), IGF-1 < -2.0 SDS on 2 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 an 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 1 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":"156-166"},"PeriodicalIF":5.3,"publicationDate":"2025-06-30","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}

{"title":"Steroidogenic factor-1 regulates a core set of target genes to promote malignancy in adrenocortical carcinoma.","authors":"João C D Muzzi, Carmen Ruggiero, Mabrouka Doghman-Bouguerra, Maísa E Colodel, Jessica M Magno, Jean S S Resende, Nelly Durand, Juliana F de Moura, Larissa M Alvarenga, Luciane R Cavalli, Bonald C Figueiredo, Enzo Lalli, Mauro A A Castro","doi":"10.1093/ejendo/lvaf138","DOIUrl":"10.1093/ejendo/lvaf138","url":null,"abstract":"<p><strong>Objective: </strong>Gene dosage is at the core of the biological activity of the steroidogenic factor-1 (SF-1/NR5A1) transcription factor. Its overexpression in adrenocortical carcinoma (ACC) is associated with enhanced proliferation and invasive capacities, steroid modulation, immune suppression, and poor prognosis. Surprisingly, 3 independent studies showed less than 10% agreement in identifying SF-1-regulated genes in the same ACC cell line, raising concerns about technical reproducibility and methodological consistency. This study aimed to reconcile discrepancies in SF-1-regulated gene identification across independent studies using a systematic approach.</p><p><strong>Design and methods: </strong>We reanalysed datasets from those studies using an in silico SF-1 regulon obtained from ACC TCGA data as an external reference to evaluate transcriptional patterns. Additionally, we assessed how threshold selection impacts the overlap between experiments and optimized this process. Furthermore, we performed functional experiments to evaluate how variations in SF-1 dosage impact target gene expression.</p><p><strong>Results: </strong>Our analysis revealed comparable transcriptional patterns across all studies, reconciling transcriptional signatures and phenotypes. Threshold optimization identified consensus sets of genes responsive to SF-1 perturbations. Functional experiments confirmed that variations in SF-1 dosage significantly impact gene expression, explaining discrepancies in previous studies, and evidenced negative autoregulation of the SF-1 transcript by its encoded protein both in ACC cells and in a mouse model of Sf-1 overexpression in the adrenal cortex.</p><p><strong>Conclusions: </strong>Our findings deepen our understanding of SF-1 regulatory activity in ACC and demonstrate that dosage is critical for observed gene expression patterns. Our integrative approach improves reproducibility and biological interpretation, offering a framework to reconcile cross-study findings.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"135-145"},"PeriodicalIF":5.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thyroid strain in pregnancy: a nationwide study of iodine nutrition and thyroglobulin among Faroese pregnant women.","authors":"Herborg Líggjasardóttir Johannesen, Anna Sofía Veyhe, Pál Weihe, Maria Skaalum Petersen, Stine Linding Andersen, Stig Andersen","doi":"10.1093/ejendo/lvaf132","DOIUrl":"10.1093/ejendo/lvaf132","url":null,"abstract":"<p><strong>Objective: </strong>Abnormal thyroid function is particularly problematic in pregnant women. Iodine is important to maintain normal thyroid function, and the World Health Organization (WHO) recommends a raised iodine intake in pregnant compared with non-pregnant adults. The raised iodine intake level from 100 to 150 µg/L includes a safety margin, and we hypothesized that the thyroid is not strained until urinary iodine concentration (UIC) is below 100 μg/L.</p><p><strong>Design: </strong>Nationwide cross-sectional study.</p><p><strong>Setting: </strong>Routine prenatal care at the National Hospital System of the Faroe Islands, 2020-2022.</p><p><strong>Participants: </strong>A total of 623 pregnant women, representing 63% of all pregnancies in the Faroe Islands during the study period, with no known thyroid disease.</p><p><strong>Exposure: </strong>Iodine-containining dietary intake was assessed indirectly through urinary iodine concentration (UIC) measured on spot urine using the Sandell-Kolthoff reaction.</p><p><strong>Main outcome: </strong>The primary outcomes were serum Thyroglobulin (s-Tg) and thyrotropin (TSH) concentration serving as indicators of potential thyroid strain and thyroid function.</p><p><strong>Measures: </strong>UIC and TSH was measured in all participants. sS-Tg was measured in a randomly selected subset of 236 participants.</p><p><strong>Results: </strong>Women were seen in median gestational week 20. None had elevated TSH; the median UIC was 108 µg/L, and the median s-Tg was 10.3 µg/L. Serum Tg differed only for the group with UIC below 50 µg/L (P = .02), but not when UIC was above 50 µg/L. TSH increased with higher UIC (P < .001).</p><p><strong>Conclusions and relevance: </strong>Thyroglobulin levels increased only in the group of Faroese pregnant women with UIC below 50 µg/L, indicating that strain on the thyroid gland was seen with low UIC levels parallel to that of non-pregnant adults. Our results suggest that the UIC limit recommended in pregnancy may be overly strict and warrant reconsideration to balance health efficacy.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"97-105"},"PeriodicalIF":5.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12230741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511721","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}

{"title":"Disrupted ACTH and cortisol response to osmotic and non-osmotic stress in patients with arginine vasopressin deficiency.","authors":"Andi Nikaj, Cihan Atila, Irina Chifu, Emanuele Ferrante, Zoran Erlic, Juliana B Drummond, Rita Indirli, Roosmarijn Drexhage, Andrew S Powlson, Mark Gurnell, Beatriz S Soares, Johannes Hofland, Felix Beuschlein, Martin Fassnacht, Bettina Winzeler, Julie Refardt, Mirjam Christ-Crain","doi":"10.1093/ejendo/lvaf119","DOIUrl":"10.1093/ejendo/lvaf119","url":null,"abstract":"<p><strong>Objective: </strong>Arginine vasopressin (AVP), synthesized in the hypothalamus and stored in the posterior pituitary, regulates osmotic balance and stress responses. During stress, AVP enhances corticotropin-releasing hormone-stimulated adrenocorticotropic hormone (ACTH) secretion, with cortisol and AVP providing negative feedback regulation. Disruption in AVP production might impair this feedback, leading to sustained cortisol elevations. The current analysis aims to investigate the effect of hypertonic saline (osmotic stress) and arginine infusion (non-osmotic stress) on the hypothalamic-pituitary-adrenal (HPA) axis response between patients with AVP-Deficiency and primary polydipsia (PP).</p><p><strong>Design: </strong>Secondary sub-analysis of a prospective diagnostic study conducted at seven tertiary centers that utilized hypertonic saline and arginine infusion for diagnostic evaluation of patients with hypotonic polyuria-polydipsia syndrome.</p><p><strong>Methods: </strong>ACTH and cortisol levels were measured at baseline and the expected peak for both stimulation tests and groups. A pooled linear mixed-effects model (without stimulation type as a variable) was used to compare hormone responses between groups, followed by stimulation test-specific linear regression models to assess differences between both tests.</p><p><strong>Results: </strong>Twenty patients with AVP-Deficiency and 10 patients with PP were included. In the pooled analysis, patients with AVP-Deficiency showed a significantly greater increase in plasma ACTH [7.0 ng/L (95% CI, 0.8-13.3), P = .04] and plasma cortisol [106 nmol/L (95% CI, 24-188), P = .02] compared to patients with PP. Upon hypertonic saline, the changes in plasma ACTH [0.3 ng/L (95% CI, -10.0 to 11.0)] and plasma cortisol [78 nmol/L (95% CI, -32 to 188)] were similar. However, upon arginine infusion, plasma ACTH [9.2 ng/L (95% CI, 1.8-17)] and plasma cortisol [141 nmol/L (95% CI, 40-242)] increases were significantly greater in patients with AVP-Deficiency.</p><p><strong>Conclusion: </strong>An altered ACTH and cortisol response pattern to stress in patients with AVP-Deficiency was observed, indicating impaired regulation of the HPA axis. This alteration was primarily driven by differences observed for non-osmotic stress.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"1-9"},"PeriodicalIF":5.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274502","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":"Predicting treatment outcome in congenital adrenal hyperplasia using urine steroidomics and machine learning.","authors":"Ozair Abawi, Grit Sommer, Michael Grössl, Ulrike Halbsguth, Therina du Toit, Sabine E Hannema, Christiaan de Bruin, Evangelia Charmandari, Erica L T van den Akker, Alexander B Leichtle, Christa E Flück","doi":"10.1093/ejendo/lvaf121","DOIUrl":"10.1093/ejendo/lvaf121","url":null,"abstract":"<p><strong>Objective: </strong>Treatment monitoring of individuals with congenital adrenal hyperplasia (CAH) remains unsatisfactory. Comprehensive 24 h urine steroid profiling provides detailed insight into adrenal steroid pathways. We investigated whether 24 h urine steroid profiling can predict treatment control in children and adolescents with CAH using machine learning (ML).</p><p><strong>Design: </strong>Prospective observational cohort study.</p><p><strong>Methods: </strong>This study included children with 21-hydroxylase deficiency. On 24 h urines of 2 consecutive visits 40 steroids were measured by gas chromatography-mass spectrometry. Treatment outcome was clinically classified as undertreated, optimally treated or overtreated. We used sparse partial least squares discriminant analysis (sPLS-DA) to investigate prediction of treatment outcome. We computed area under the ROC-curve (AUC) of 2 sPLS-DA models: (1) using only 24 h urine metabolites and (2) adding clinical variables.</p><p><strong>Results: </strong>We included 112 visits (68 optimal, 44 undertreatment) from 59 patients: 27 (46%) girls, 46 (78%) classic CAH, and 19 (32%) prepubertal. Mean age at first visit was 11.9 ± 4.0 years and mean BMI SDS 0.6 ± 1.1. SPLS-DA using 24 h urine metabolites showed clear clustering of optimally treated patients on 2 components, while undertreated patients were more heterogeneous (AUC 0.88). The model selected pregnanetriol and 17α-hydroxypregnanolone contributing to excluding optimal treatment and 5 metabolites contributing to excluding undertreatment: 17β-estradiol, cortisone, tetrahydroaldosterone, androstenetriol, and etiocholanolone. Addition of clinical variables marginally improved classification (AUC 0.90).</p><p><strong>Conclusions: </strong>Using ML on 24 h urine steroid profiling predicted treatment outcome in children with CAH, even in the absence of clinical data, suggesting that routine comprehensive 24 h urine steroid profiling could improve treatment monitoring in CAH.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"10-20"},"PeriodicalIF":5.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293567","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":"Large-scale screening and functional study of DUOXA2 variant in 599 Chinese patients with congenital hypothyroidism.","authors":"Hai-Yang Zhang, Cao-Xu Zhang, Feng-Yao Wu, Chen-Yang Wu, Fei-Yang Zhang, Liu Yang, Yue Zhang, Huai-Dong Song, Shuang-Xia Zhao","doi":"10.1093/ejendo/lvaf123","DOIUrl":"10.1093/ejendo/lvaf123","url":null,"abstract":"<p><strong>Objective: </strong>Dual oxidase maturation factor 2 (DUOXA2) is necessary for proper cellular localization and maturation of functional dual oxidase 2 (DUOX2). It is an attractive candidate gene for congenital hypothyroidism (CH). This study aimed to identify DUOXA2 variants in Chinese CH patients, analyze the function of the variants, and explore the genotype-phenotype relationship.</p><p><strong>Design: </strong>A total of 599 patients with CH were recruited for screening DUOXA2 variants by performing targeted next-generation sequencing or whole exome sequencing. Detailed clinical data were collected for statistical analysis. The biological function of the identified DUOXA2 variants was detected in vitro.</p><p><strong>Results: </strong>A total of 13 variants including 6 novel variants were detected in the DUOXA2 gene, showing a 6.7% rate in variant carrying (40/599). Ten variants disrupted the enzyme activity of DUOX2, resulting in impaired H2O2 production. In addition, we found that oligogenic mutation patterns within the DUOX system were prevalent among Chinese patients with CH. The cases in the DUOXA2-mutated group were milder and more likely to manifest as normal thyroid size than those in the nonmutated group.</p><p><strong>Conclusions: </strong>Our study greatly expanded the variant spectrum of the DUOXA2 gene. Pedigree and in vitro functional studies improved the accuracy of genetic counseling. The genotype-phenotype relationship of DUOXA2 broadened the understanding of the CH phenotype spectrum.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"21-30"},"PeriodicalIF":5.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283042","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}