Endocrine Abstracts

Disorders of sex development (DSD) include a conglomerate of rare conditions with discrepancy of the chromosomal, gonadal or phenotypic sex. Since the last 2 decades the genetic causes and the pathogenesis have been identified in many patients with DSD. Multidisciplinary clinical care as decision on the sex of rearing, genital surgery, hormone therapies and psychological support has a life-long impact on the affected persons. However, previous clinical outcome studies of DSD w...

Background: In patients with phaeochromocytoma, sudden and/or chronic exposure to catecholamines may predispose to cardiac pathology, including left ventricular (LV) hypertrophy, myocardial infarction, stress-induced cardiomyopathy and heart failure. We conducted the first prospective, multicentre study using cardiovascular magnetic resonance (CMR) imaging to describe the variety and incidence of cardiac abnormalities in phaeochromocytoma.Methods: Fifty ...

Steroid sulfatase (STS) cleaves the sulfate moiety off steroid sulfates, including DHEAS, the inactive sulfate ester of the adrenal androgen precursor DHEA. Deficient DHEA sulfation, the opposite enzymatic reaction to that catalysed by STS, results in androgen excess by increased conversion of DHEA to active androgens. STS deficiency (STSD) due to deletions or inactivating mutations in the X-linked STS gene manifests with ichthyosis, but androgen homeostasis in STSD h...

Background: Patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-OHD-CAH) have poor health outcomes due to failure of currently available glucocorticoid preparations to control adrenocorticotropic hormone-driven androgen excess. We investigated whether modified-release hydrocortisone (MR-HC), which mimics the physiological circadian cortisol rhythm, could improve androgen control.Methods: 122 patients with 21-OHD-CAH ...

Context: Cytochrome P450 (CYP) 17A1 is located at major branch points of steroidogenesis exerting two distinct catalytic activities: 17α-hydroxylase generates glucocorticoid precursors and 17,20-lyase generates the principal sex steroid precursor dehydroepiandrosterone (DHEA). CYP17A1 deficiency (17OHD) is a rare form of congenital adrenal hyperplasia. In severe 17OHD, affected individuals typically present with both glucocorticoid and sex steroid deficiency and mineraloc...

Steroid 17α-hydroxylase (CYP17A1) exerts two distinct activities that catalyze conversion reactions at key branch points in steroidogenesis. CYP17A1 17α-hydroxylase activity is the key step in cortisol synthesis whereas CYP17A1 17,20 lyase activity generates sex steroid precursors. Inactivating CYP17A1 mutations result in CYP17A1 deficiency (17OHD), a rare form of congenital adrenal hyperplasia that classically presents with combined glucocorticoid and sex steroid de...

In congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency a genotype-phenotype correlation exists for paediatric cohorts, helping to predict the severity of disease expression. Data on the correlation in adults is lacking. Here we report the genetic analysis of the UK CaHASE cohort, comprising CAH adults seen at 17 endocrine tertiary care centres. CYP21A2 mutation analysis was performed in 153 patients (median age 35 (range 18–69) yrs; 103 f, 50 m) by multi...

Background: Adrenal masses are discovered in 5% of abdominal imaging scans. Accuracy of currently available imaging tests to diagnose malignancy is poor. In a proof-of-concept study (JCE&M 2011;96(12):3775-84), we had demonstrated 90% sensitivity and specificity in detecting adrenocortical carcinoma (ACC) for urine steroid metabolomics, the combination of mass spectrometry-based steroid profiling and machine learning-based data analysis. This diagnostic performance is supe...

Adrenocortical Carcinoma (ACC) is an aggressive malignancy with poor response to chemotherapy. Here we evaluated a potential new treatment target for ACC, focusing on the mitochondrial NADPH generator Nicotinamide Nucleotide Transhydrogenase (NNT). NNT has a central role within mitochondrial antioxidant pathways, protecting cells from oxidative stress. Inactivating human NNT mutations result in congenital adrenal insufficiency. We hypothesized NNT silencing in ACC cells will i...

BackgroundAdrenocortical Carcinoma (ACC) is a rare aggressive cancer with a heterogeneous behaviour. Disease surveillance relies on frequent imaging, which has limited sensitivity and results in significant radiation exposure. Aim of the study was to investigate the role of circulating cell-free DNA (ccfDNA) as a biomarker for prognostication and disease monitoring in ACC.MethodsccfDNA was extracted from 1&#8...