European Journal of Endocrinology最新文献

{"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":"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":"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. 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>Design: </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 3999 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 3 months after SSRIs/venlafaxine initiation. After 1 year, the aOR was 1.30 (95% CI: 0.97-1.75). During the first 2 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":"179-187"},"PeriodicalIF":5.3,"publicationDate":"2025-06-30","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}

{"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}

{"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":"Diagnostic strategies for central adrenal insufficiency in clinical practice: authors' response.","authors":"Linus Haberbosch, Christian J Strasburger, Lukas Maurer, Knut Mai","doi":"10.1093/ejendo/lvaf126","DOIUrl":"10.1093/ejendo/lvaf126","url":null,"abstract":"","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"L3-L4"},"PeriodicalIF":5.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293565","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":"Osteoporotic fracture risk in hypoparathyroidism following total thyroidectomy: a retrospective nationwide cohort study.","authors":"Eu Jeong Ku, Won Sang Yoo, Yu Been Hwang, Subin Jang, Jooyoung Lee, Shinje Moon, Eun Kyung Lee, Hwa Young Ahn","doi":"10.1093/ejendo/lvaf128","DOIUrl":"10.1093/ejendo/lvaf128","url":null,"abstract":"<p><strong>Objective: </strong>Hypoparathyroidism is an uncommon but significant complication of total thyroidectomy. As the incidence of thyroid cancer increases, the prevalence of hypoparathyroidism also increases. However, its effect on the risk of osteoporotic fractures remains poorly understood. We aimed to evaluate the risk of osteoporotic fractures in patients with postoperative hypoparathyroidism compared with that in a matched control group.</p><p><strong>Design: </strong>This retrospective cohort study included 417 patients with hypoparathyroidism who had undergone total thyroidectomy for thyroid cancer (TC with hypoP) and 2085 matched controls from the Korean National Health Insurance Service-National Sample Cohort.</p><p><strong>Methods: </strong>The osteoporotic fracture rates and associated risk factors were analyzed in comparison after propensity score matching.</p><p><strong>Results: </strong>During a median follow-up period of 5.07 years (interquartile range 2.19-7.38), postoperative hypoparathyroidism was not associated with a significantly greater risk of osteoporotic fractures than that in the control group (hazard ratio [HR] 0.86, 95% confidence interval [CI], 0.59-1.24, P = .406). Age-specific analysis showed a trend toward higher fracture incidence in patients aged <50 years (HR 1.31, 95% CI, 0.53-3.22, P = .558) and a decreasing trend in those aged ≥50 years (HR 0.75, 95% CI, 0.51-1.12, P = .163), although the differences were not statistically significant. No significant differences in fracture risk were observed between the TC with and without hypoP groups across all fracture sites. The frequency of osteoporotic medication use was higher in the TC with hypoP group than in the control group, particularly among women aged <50 years.</p><p><strong>Conclusions: </strong>Hypoparathyroidism after total thyroidectomy does not appear to increase the risk of osteoporotic fractures compared with that in matched controls in clinical practice.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"39-47"},"PeriodicalIF":5.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505223","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":"Autoimmune thyroiditis in paediatric thyroid cancer: clinical features and outcomes.","authors":"Michaela Kuhlen, Marina Kunstreich, Desiree Dunstheimer, Niklas Aumann, Kerstin Lorenz, Markus Luster, Kurt W Schmid, Antje Redlich","doi":"10.1093/ejendo/lvaf133","DOIUrl":"10.1093/ejendo/lvaf133","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate clinical characteristics and survival outcomes of paediatric differentiated thyroid carcinoma (paedDTC) in patients with and without autoimmune thyroiditis (AIT).</p><p><strong>Design: </strong>Retrospective cohort analysis of paedDTC patients with and without AIT, prospectively enrolled in the German Malignant Endocrine Tumour Registry between 1997 and 2024.</p><p><strong>Methods: </strong>We analysed data from paediatric patients (<18 years) with histopathologically confirmed DTC, stratified by AIT status. Variables included demographics, tumour characteristics, lymph node involvement, and metastasis. Survival outcomes were assessed using Kaplan-Meier estimates.</p><p><strong>Results: </strong>Among 401 evaluable patients, 16.0% had AIT. AIT patients were significantly older at diagnosis (P < .001) and showed a non-significant tendency toward higher female predominance (P = .098). Patients with AIT demonstrated significantly lower rates of distant metastasis (7.5% vs. 22.2%, P = .014) compared with those without AIT. No significant differences were observed in tumour size, capsule invasion, lymphatic or vascular invasion, soft tissue infiltration, or multifocality. A tendency toward improved event-free survival (EFS) was observed in AIT patients (87.5% vs. 72.1%, P = .255), while overall survival (OS) was comparable (91.8% vs. 86.0%, P = .167) during the study period. Among patients with known AIT history, paedDTC was significantly more frequently diagnosed through surveillance compared with non-AIT patients (44.2% vs. 28.3%, P = .022).</p><p><strong>Conclusions: </strong>AIT was present in 16% of paedDTC patients and was associated with reduced distant metastasis. A tendency toward improved EFS but similar OS during the follow-up period was observed. Earlier detection through surveillance in AIT patients may contribute to these findings, warranting further investigation into underlying biological mechanisms.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"48-55"},"PeriodicalIF":5.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511720","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":"Unexpected discrepancies between steroid intra-tissular content in adrenal tumors and clinical diagnosis of steroid excess.","authors":"Fidéline Bonnet-Serrano, Louis Thomeret, Nesrine Benanteur, Patricia Vaduva, Florian Violon, Lucas Bouys, Bruno Ragazzon, Annabel Berthon, Karine Perlemoine, Hortense Wilmot-Roussel, Corinne Zientek, Samir Nakib, Martin Gaillard, Mathilde Sibony, Christelle Laguillier-Morizot, Marie-Claude Menet, Laurence Guignat, Rossella Libe, Lionel Groussin, Jean Guibourdenche, Anne Jouinot, Guillaume Assié, Jérôme Bertherat","doi":"10.1093/ejendo/lvaf129","DOIUrl":"10.1093/ejendo/lvaf129","url":null,"abstract":"<p><strong>Objective: </strong>Adrenocortical tumor (ACT) morbidity is associated with steroid secretion, depending on tumor type. Indeed, adrenal steroidogenesis is a finely regulated process, altered in ACT. These alterations are usually characterized by blood steroid assays, also depending on steroid gonadal production and metabolism. Our aim was to determine steroid content directly in ACT tissues and to compare it with clinical diagnosis of steroid excess.</p><p><strong>Methods: </strong>A profile of 13 steroids was analyzed in ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (Thermo Fisher Scientific®) in frozen tissue samples from 75 ACT, 7 Cushing's disease, and 9 normal adrenals.</p><p><strong>Results: </strong>Steroid levels were 10-1000 times higher in tissue from normal adrenal than normal concentrations expected in blood. Concentration ratios between tissue from normal adrenal and blood reference values were lower for distal products than for steroid precursors. In adrenocortical cancers, intra-tissular steroid content was lower than in unilateral benign tumors despite clear clinical steroid excess. Unexpectedly, in overt-Cushing adenomas, intra-tissular cortisol levels were not higher and androstenedione levels were not lower than in non-functioning adenomas. Adrenal differentiation score based on transcriptome was well correlated with intra-tissular cortisol levels.</p><p><strong>Conclusion: </strong>Discrepancies observed between steroid levels measured in ACT tissue and clinical diagnosis of steroid excess suggest a dysregulation of steroid export depending on tumor type, opening new perspectives for diagnosis and treatment of steroid excess.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"106-116"},"PeriodicalIF":5.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293568","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}