European Journal of Endocrinology最新文献

{"title":"Genetic predisposition to adiposity, and type 2 diabetes: the role of lifestyle and phenotypic adiposity.","authors":"Mengrong Zhang, Joey Ward, Rona J Strawbridge, Jana J Anderson, Carlos Celis-Morales, Jill P Pell, Frederick K Ho, Donald M Lyall","doi":"10.1093/ejendo/lvaf084","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf084","url":null,"abstract":"<p><strong>Aims: </strong>Genetic predisposition to adiposity is associated with type 2 diabetes (T2D), even in the absence of phenotypic adiposity (obesity and central obesity). We aimed to quantify the overall contribution of obesity and modifiable lifestyle factors to the association between genetic predisposition to adiposity and the development of T2D.</p><p><strong>Methods: </strong>This prospective cohort study involved 220 703 White British participants from the UK Biobank. It examined the associations between genetic predisposition to adiposity [body mass index polygenic risk (BMI-PRS) and waist-hip ratio polygenic risk (WHR-PRS)] and incident T2D, as well as interactions and mediation via lifestyle factors (diet quality, physical activity levels, total energy intake, sleep duration, and smoking and alcohol intake) and phenotypic adiposity.</p><p><strong>Results: </strong>People with high phenotypic adiposity and high adiposity PRS values (>1 SD above the mean) had the highest risk of incident T2D (versus non-obese/central obese and non-high PRS). This was the case for BMI-PRS [hazard ratio (HR) = 3.72] and WHR-PRS (HR = 4.17). Lifestyle factors explained 30.5% of the BMI-PRS/T2D association (2.0% mediation; 28.5% effect modification), and lifestyle and obesity together explained 92.1% (78.8% mediation; 13.3% effect modification). Lifestyle factors explained 20.4% of the WHR-PRS/T2D association (3.4% mediation; 17.0% effect modification), and lifestyle and central obesity together explained 72.8% (41.1% mediation; 31.7% effect modification).</p><p><strong>Conclusions: </strong>Whilst phenotypic adiposity explains a large proportion of the association between BMI-PRS/WHR-PRS and T2D, modifiable lifestyle factors also make contributions. Promoting healthy lifestyles among people prone to adiposity is important in reducing the global burden of T2D.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"192 5","pages":"549-557"},"PeriodicalIF":5.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12056655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976170","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":"Sexual dimorphism in benign adrenocortical tumours.","authors":"Onnicha Suntornlohanakul, Cristina L Ronchi, Wiebke Arlt, Alessandro Prete","doi":"10.1093/ejendo/lvaf088","DOIUrl":"10.1093/ejendo/lvaf088","url":null,"abstract":"<p><p>Benign adrenocortical tumours are the most common adrenal neoplasms. Evidence over the past few decades has highlighted sex differences in their prevalence, clinical characteristics, and treatment outcomes. Cortisol-producing adenomas causing either Cushing's syndrome, particularly those with PRKACA or GNAS somatic mutations associated with a more severe phenotype, or mild autonomous cortisol secretion (MACS) are more commonly observed in women. The mechanisms underpinning this sexual dimorphism remain to be fully elucidated. Studies in mice have revealed a protective role of androgens in males, leading to a decelerated growth rate of adrenocortical cells. Furthermore, evidence from human adrenal tumour tissue suggests that oestrogen, progesterone, and luteinising hormone/choriogonadotropin signalling in the adrenal cortex may play a role in adrenal tumourigenesis and steroid production. Clinically, this is supported by the increased incidence of cortisol-producing adrenocortical adenomas or nodular hyperplasia during puberty, pregnancy, and menopause. Notably, women with MACS seem to be more vulnerable to the harmful effects of cortisol excess and carry a higher mortality risk than men. Women with aldosterone-producing adenomas have a higher prevalence of somatic KCNJ5 mutations than men, and patients harbouring these mutations are likely to have more favourable clinical outcomes after adrenalectomy. In this review, we summarise the possible mechanisms behind the sexual dimorphism of benign adrenocortical tumours and provide an up-to-date overview of the sex-specific differences in their prevalence, clinical presentation, and outcomes, focusing on cortisol and aldosterone excess. Considering sexual dimorphism is crucial to guide diagnosis and management, and to counsel these patients for optimised care.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"192 5","pages":"R1-R12"},"PeriodicalIF":5.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12068951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990543","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":"Increased insulin-like growth factor-1 concentrations in paediatric suprasellar low-grade glioma: an international multicentre study.","authors":"Ichelle M A A van Roessel, Boudewijn Bakker, Antoinette Y N Schouten-van Meeteren, Wim J E Tissing, Hoong-Wei Gan, Hanneke M van Santen","doi":"10.1093/ejendo/lvaf095","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf095","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study was to assess the prevalence of elevated insulin-like growth factor (IGF)-1 in children with suprasellar low-grade glioma (LGG) and explore the course of IGF-1 over time and its association with anthropometrics, hypothalamic syndrome, tumour characteristics, and tumour behaviour.</p><p><strong>Design: </strong>This retrospective study included children from the Netherlands and the United Kingdom diagnosed with a suprasellar LGG under the age of 18 between 2003 and 2023, with a minimum 1-year follow-up. Elevated IGF-1 was defined as IGF-1 standard deviation score (SDS) >+2.0 for age and biological sex, without growth hormone use.</p><p><strong>Results: </strong>We included 235 patients with a median age at brain tumour diagnosis of 3.8 years (IQR 1.7-7.1). Elevated IGF-1 was observed in 73 patients (31.1%) at any time point. At tumour diagnosis, 15.2% of the 138 children tested showed elevated IGF-1. Elevated IGF-1 was associated with younger age at tumour diagnosis (P = .004), neurofibromatosis type 1 (NF1; P = .028), and diencephalic syndrome (P = .047). In 55 of the 73 patients with elevated IGF-1 (75.3%), IGF-1 normalized spontaneously over time. Final height SDS corrected for target height SDS was not associated with having had an elevated IGF-1 (P = .113). No difference was found in the number of tumour progressions.</p><p><strong>Conclusions: </strong>Increased IGF-1 concentrations are commonly observed in children with suprasellar LGG, especially in younger children, those with an NF1 mutation, or during underweight. Elevation of IGF-1 can resolve over time, and the absence of an effect on final height or on tumour progressions seems reassuring.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"192 5","pages":"641-650"},"PeriodicalIF":5.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119021","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":"Blood pressure and its associations in 554 children and young people with congenital adrenal hyperplasia.","authors":"Neil R Lawrence, Irina Bacila, Joseph Tonge, Jeremy Dawson, Gary S Collins, Zi-Qiang Lang, Jillian Bryce, Malika Alimussina, Minglu Chen, Salma Rashid Ali, Safwaan Adam, Erica L T van den Akker, Tânia Aparecida Sartori Sanchez Bachega, Federico Baronio, Niels Holtum Birkebæk, Walter Bonfig, Hedi Claahsen-van der Grinten, Martine Cools, Eduardo Correa Costa, Miguel Debono, Liat de Vries, Christa E Flück, Gabriella Gazdagh, Ayla Güven, Sabine E Hannema, Violeta Iotova, Hetty J van der Kamp, Ruth Krone, Sofia Leka-Emiri, María Clemente-León, Corina Raducanu Lichiardopol, Renata L Markosyan, Tatjana Milenkovic, Mirela Costa de Miranda, Uta Neumann, John Newell-Price, Şükran Poyrazoğlu, Ursina Probst-Scheidegger, Gianni Russo, Luisa De Sanctis, Sumudu Nimali Seneviratne, Marianna Rita Stancampiano, Rieko Tadokoro-Cuccaro, Ajay Thankamony, Ana Vieites, Malgorzata Wasniewska, Diego Yeste, Jeremy Tomlinson, S Faisal Ahmed, Nils Krone","doi":"10.1093/ejendo/lvaf060","DOIUrl":"10.1093/ejendo/lvaf060","url":null,"abstract":"<p><strong>Background: </strong>Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) affects approximately 1 in 15 000 individuals. We leveraged the power of multicentre registry data to assess the trend and predictors of blood pressure (BP) within children and young persons with 21OHD to inform monitoring strategies.</p><p><strong>Method: </strong>Data from the International CAH Registry in patients younger than 20 years was compared to normative values. Values of BP were modeled to create reference curves, multiple change point analysis applied to quantify the difference with normative data. Covariate adjustment was informed by a directed acyclic graph, prior to joint outcome regression modeling to accurately assess predictors of BP.</p><p><strong>Results: </strong>A total of 6436 visits within 554 patients (52.5% females) showed BP-Standard deviation scores (SDS) were higher at younger ages. Patients under five years had systolic BP-SDS of 1.6 (Q1:0.6-Q3:2.7) decreasing to 1.0 (Q1:0.2-Q3:1.8) over 5 years, equating to 31.0% over the 95th centile decreasing to 15.0%. Higher doses of fludrocortisone were associated with a small increase in systolic BP equivalent to 1.2 mmHg with every 100 µg extra fludrocortisone. Renin of 100µU/mL was associated with 4.6 mmHg lower systolic BP than a renin of 1µU/mL, higher 17OH-progesterone and androstenedione also predicted lower systolic and diastolic BP (P < .05).</p><p><strong>Conclusion: </strong>Higher BP in children with 21OHD is common and particularly pronounced at a younger age, but may not be attributable to excessive mineralocorticoid replacement. There is a need to improve our understanding of the determinants of this raised BP as well as its long-term effects.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"529-539"},"PeriodicalIF":5.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143784371","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 relationship between hypoprolactinemia and cardiometabolic health in women.","authors":"Thang S Han, Anke Hannemann, Riikka Arffman, Nele Friedrich, Till Ittermann, Robin Wilkening, Terhi Piltonen, Christopher Henry Fry, Ana B Crujeiras, Felipe F Casanueva","doi":"10.1093/ejendo/lvaf101","DOIUrl":"10.1093/ejendo/lvaf101","url":null,"abstract":"<p><strong>Background: </strong>An evidence-based definition for the lower reference limit of serum prolactin (PRL) is lacking. We recently examined the European Male Ageing Study (EMAS) data and derive a threshold set at 3.0 ng/mL for hypoprolactinemia in men. Here, we identified the lower reference limit for PRL in women.</p><p><strong>Methods: </strong>We used data from the Study of Health of Pomerania (SHIP-START, Germany, discovery cohort), and the Women's Health Study (WENDY, Finland, validation cohort). The two-sigma empirical rule was applied to obtain a threshold at 2.5% of the log10 PRL distribution. Logistic and Cox regressions were used to examine the association between PRL and cardiometabolic outcomes at baseline and follow-up, respectively.</p><p><strong>Results: </strong>There were 2048 women aged 20-81 year from SHIP-START and 1730 women aged 33-37 year from WENDY. The low serum PRL threshold was derived at 2.60 ng/mL for premenopausal women and 2.29 ng/mL in women of all ages from SHIP-START, and 4.84 ng/mL in WENDY. These thresholds were not far off from that previously identified in men (3 ng/mL). In SHIP-START, we further found that compared to PRL levels of 5.0-34.9 ng/mL, lower PRL level were more commonly associated with type-2 diabetes and metabolic syndrome at baseline. Moreover, after a median of 12 year of follow-up (IQR = 6.9-15.8 year), the risk of developing myocardial infarction was greater in women with PRL < 2.30 ng/mL (SHIP-START criteria): adjusted hazard ratio = 4.19 (95% CI: 1.74-10.12), and in women with PRL < 3 ng/mL (EMAS criteria): hazard ratio = 2.74 (95% CI: 1.44-5.21).</p><p><strong>Conclusions: </strong>Our data suggests that a serum PRL level lower than 3 ng/mL could be adopted for identifying PRL-associated cardiometabolic disease in both sexes.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"662-670"},"PeriodicalIF":5.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987664","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":"Altered brain function and structure in youth-onset type 2 diabetes.","authors":"Allison L B Shapiro, Phoom Narongkiatikhun, Ye Ji Choi, Greta Wilkening, Kalie L Tommerdahl, Hailey E Hamson, Laura Pyle, Petter Bjornstad","doi":"10.1093/ejendo/lvaf098","DOIUrl":"10.1093/ejendo/lvaf098","url":null,"abstract":"<p><strong>Objective: </strong>Despite the aggressive clinical trajectory of youth-onset type 2 diabetes (Y-T2D) and consistent evidence of cognitive dysfunction and poor brain health in adults with T2D, the impact of Y-T2D on brain function and structure is understudied.</p><p><strong>Design: </strong>This study aimed to characterize brain function and structure in a cross-sectional sample of young people with Y-T2D and compare these brain attributes to peers with obesity alone (OB) or healthy weight (HW) without T2D.</p><p><strong>Methods: </strong>Brain structure and function were measured via magnetic resonance imaging. Functional connectivity was estimated with a seed-to-voxel analysis and gray matter (GM) volume differences explored between groups.</p><p><strong>Results: </strong>Forty young adult participants were included (Y-T2D: n = 12, mean [±SD] age 25.0 ± 7.2 years, diabetes duration 6.5 ± 6.7 years; OB: n = 8, age 19 ± 1.6 years; HW: n = 20, age 22.9 ± 4.1 years). The Y-T2D group showed stronger functional connectivity between the salience network and default mode network, compared to both the OB and HW groups (P < .05 for all, respectively). The Y-T2D group had reduced GM volume in regions associated with executive functioning, language, and visual processing relative to the OB and HW groups (P < .001 for all, respectively).</p><p><strong>Conclusions: </strong>Y-T2D is associated with distinct alterations in brain function and structure, providing evidence of potentially compromised brain health in this clinical population.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"671-679"},"PeriodicalIF":5.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12100494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992786","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":"Primary adrenal insufficiency in patients with CPOX gene mutations.","authors":"Elif Kelestemur, Murat Hakki Yarar, Busra Gurpinar Tosun, Meryem Karaca, Ayse Mine Yilmaz Goler, Betul Karademir Yilmaz, Ozge Yapici, Gulden Gokcay, Tulay Guran","doi":"10.1093/ejendo/lvaf089","DOIUrl":"10.1093/ejendo/lvaf089","url":null,"abstract":"<p><strong>Background: </strong>Harderoporphyria arises from biallelic CPOX gene mutations, leading to coproporphyrinogen oxidase deficiency in the inner mitochondrial membrane. The impact of CPOX gene mutations on adrenal function remains poorly understood.</p><p><strong>Objective: </strong>Characterizing primary adrenal insufficiency (PAI) in 2 siblings with harderoporphyria.</p><p><strong>Methods: </strong>Clinical data were recorded, and genetic analysis was performed by whole genome sequencing (WGS). Plasma steroids and urinary porphyrins were measured by liquid chromatography-mass spectrometry and high-performance liquid chromatography, respectively. Mitochondrial function was assessed using the mitochondrial membrane potential (MMP) assay in peripheral blood mononuclear cells.</p><p><strong>Results: </strong>Patients were diagnosed with PAI at 4.5 years (P1, 46,XY) and 7 months (P2, 46,XX). P1 had atypical genitalia and developed primary gonadal insufficiency and non-immune diabetes at ages 6 and 10, respectively. Both patients had a history of microcytic anaemia, haemolysis, cholestasis, hepatosplenomegaly in early infancy, hyperpigmentation, abdominal pain, nystagmus, optic atrophy, and mild lactic acidosis in early childhood. WGS revealed a homozygous c.83_85del, p.S28* variant in CPOX. Oxidative damage to mitochondria was shown by decreased MMP in patients compared with controls (P < .0001). Hormonal assessment indicated severe PAI, suggestive of combined CYP11A1 and CYP11B1 deficiency.</p><p><strong>Conclusions: </strong>CPOX gene mutations cause a mixed model of PAI, affecting mitochondrial steroidogenic enzymes. Clinical manifestations of harderoporphyria may overlap with PAI signs.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"192 5","pages":"K31-K37"},"PeriodicalIF":5.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974326","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 influence of gender-affirming hormone therapy on serum concentrations of hormone-binding proteins.","authors":"Theresa A Stangl, Chantal M Wiepjes, Annemieke C Heijboer, Martin den Heijer","doi":"10.1093/ejendo/lvaf038","DOIUrl":"https://doi.org/10.1093/ejendo/lvaf038","url":null,"abstract":"<p><strong>Background: </strong>Corticosteroid-binding globulin (CBG), thyroid-binding globulin (TBG), sex hormone-binding globulin (SHBG), and insulin-like growth factor-binding protein 3 (IGF-BP3) regulate the bioavailability and transport of hormones, affecting hormone concentration measurements and therapy plans. This study investigates to what extent gender-affirming hormone therapy (GAHT) impacts serum concentrations of these binding proteins.</p><p><strong>Methods: </strong>This prospective study included 41 transfeminine persons starting oral or transdermal 17β-estradiol in combination with cyproterone acetate (CPA) or gonadotropin-releasing hormone analogs (GnRHa) and 38 transmasculine persons starting testosterone gel or injections. Serum concentrations of CBG (mg/L), TBG (nmol/L), SHBG (nmol/L), and IGF-BP3 (mg/L) were measured at baseline and after 3 and 12 months. Changes were analyzed using mixed models and reported as percentage change.</p><p><strong>Results: </strong>In oral estradiol and CPA users, CBG increased by 29% (95% CI, 16, 44%), TBG by 24% (95% CI, 16, 32%), SHBG by 81% (95% CI, 61, 105%) and in oral estradiol and GnRHa users by 47% (95% CI, 7, 101%), 48% (95% CI, 9, 101%), and 242% (95% CI, 104, 474%), respectively. The IGF-BP3 remained unchanged. In transdermal estradiol users, only SHBG changed (+63% [95% CI, 3, 157%]), when combined with GnRHa. In transmasculine participants, CBG, TBG, SHBG, and IGF-BP3 decreased by 13% (95% CI, -21, -4%), 11% (95% CI, -15, -6%), 43% (95% CI, -48, -36%), and 10% (95% CI, -18, -2%) respectively, with no difference in gel vs injections.</p><p><strong>Conclusion: </strong>The GAHT led to an increase of CBG, TBG, and SHBG in estradiol users, more specifically oral estradiol, and to a decrease of SHBG, CBG, TBG, and IGF-BP3 in testosterone users. Recognizing these alterations is crucial for ensuring accurate hormone measurements and optimal patient care.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":"192 5","pages":"614-620"},"PeriodicalIF":5.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076262","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":"Primary adrenal insufficiency caused by pseudo-neonatal adrenoleukodystrophy associated with biallelic ACOX1 mutations.","authors":"Didem Helvacioglu, Aylin Tugba Canbaz, Aysel Tekmenuray-Unal, Yasin Ada, Ozge Yapici, Emine Genc, Sebile Kilavuz, Busra Gurpinar Tosun, Burcu Ozturk Hismi, Tulay Guran","doi":"10.1093/ejendo/lvaf094","DOIUrl":"10.1093/ejendo/lvaf094","url":null,"abstract":"<p><strong>Background: </strong>Peroxisomal fatty acyl-CoA oxidase 1, encoded by ACOX1, initiates and limits the rate of beta-oxidation of very long-chain fatty acids (VLCFA). Biallelic ACOX1 mutations cause pseudo-neonatal adrenoleukodystrophy (PNALD). Primary adrenal insufficiency (PAI) has not been clearly characterized in the 34 PNALD patients reported to date.</p><p><strong>Objective: </strong>Characterizing PAI in a patient and her cousin with PNALD.</p><p><strong>Methods: </strong>Clinical data were recorded, and molecular etiologies were investigated using next-generation sequencing panels and 750K microarray. Plasma steroids and VLCFAs were measured via mass spectrometry.</p><p><strong>Results: </strong>A 1.5-year-old female patient was evaluated for PAI due to hyperpigmentation, hypoglycemia, hyponatremia and hyperkalemia. She had a history of severe neonatal-onset hypotonia, seizures, psychomotor/developmental delay, and neurological regression. Molecular studies revealed a homozygous deletion encompassing exons 13 and 14 of the ACOX1 gene. Biochemical analysis revealed accumulation of saturated VLCFA. Cranial magnetic resonance imaging showed T2 high-intensity areas in bilateral centrum semiovale, basal ganglia, brainstem and cerebellar white matter. High plasma ACTH, low cortisol and steroid precursors along with high plasma renin activity were compatible with a PAI other than congenital adrenal hyperplasia (non-CAH). Abdominal computerized tomography demonstrated bilateral adrenal atrophy. The cousin of the patient with PNALD developed non-CAH PAI at 7 months of age.</p><p><strong>Conclusion: </strong>Adrenal insufficiency should be considered in the phenotypic spectrum of peroxisomal disorders. Fatty acyl-CoA oxidase 1 deficiency may emerge as a peroxisomal etiology of non-CAH PAI.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"K38-K43"},"PeriodicalIF":5.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989155","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":"Real-world outcomes of finerenone in primary aldosteronism.","authors":"Thomas Uslar, Benjamín Sanfuentes, Iván Muñoz, Anand Vaidya, René Baudrand","doi":"10.1093/ejendo/lvaf099","DOIUrl":"10.1093/ejendo/lvaf099","url":null,"abstract":"<p><p>Primary aldosteronism (PA) treatment with mineralocorticoid receptor antagonists (MRAs) is effective but limited by side-effects and low potency of currently available options. Finerenone, a novel MRA, has emerged as a promising alternative but data in PA are lacking. This report presents a real-world study wherein PA patients on eplerenone were forced to switch to finerenone therapy during a national shortage. During treatment with finerenone, blood pressure and antihypertensive dose remained unchanged, but the proportion of patients with normal blood pressure and complete biochemical response was decreased (P = .004 and P = .008, respectively). The latter was determined by a reduction in direct renin concentration, a biomarker previously associated with increased cardiovascular risk in PA. Although these results could be explained by finerenone's unique pharmacokinetics and mechanism of action, further studies are needed to evaluate longitudinal outcomes associated with these findings and determine its effectiveness in PA treatment.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"K50-K53"},"PeriodicalIF":5.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075923","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}