Endocrine Abstracts

The steroid 17α-hydroxylase enzyme 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 ...

Background: The multi-tyrosine kinase inhibitor sunitinib is approved for advanced renal cell carcinoma and gastrointestinal stroma tumors. It targets both tumor vessels and malignant cells. Animal experiments have pointed to a direct adrenotoxic effect of the drug.Aims: We hypothesized that sunitinib may inhibit proliferation of adrenocortical cancer (ACC) cells and influence adrenal steroid hormone synthesis.Results: Sunitinib re...

P450 oxidoreductase (POR) transfers electrons to all microsomal P450 enzymes including CYP21A2 and CYP17A1, key enzymes of glucocorticoid and andogen synthesis, respectively. Mutant POR results P450 oxidoreductase deficiency (ORD) manifesting with glucocorticoid deficiency and disordered sex development in both sexes. Neonatal presentation with undervirilisation in boys and virilisation in girls is well described. However, there is a paucity of data on the pubertal phenotype i...

Background: The adrenal glucocorticoid, cortisol, has a distinct circadian rhythm regulated by the brain’s central pacemaker. This cortisol rhythm acts as a secondary messenger to peripheral tissues and loss of the rhythm is associated with increased morbidity and mortality. This is a specific problem in adrenal insufficiency and congenital adrenal hyperplasia (CAH). Based on pharmacokinetic modelling we have developed a modified-release formulation of hydrocortisone (MR-...

Polycystic ovary syndrome (PCOS) affects 5–10% of the female population. It is characterised by androgen excess and anovulatory infertility; several studies have reported an increased incidence of the metabolic syndrome and enhanced 5α-reductase activity in PCOS. However, the contribution of obesity to these findings has yet to be clarified. Here we have analysed metabolic status and urinary steroid metabolite excretion in 114 patients with PCOS (median age 30 (range...

Congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase (CYP21A2) deficiency is the commonest inborn error in steroid hormone biosynthesis and the most frequent cause of congenital adrenal hyperplasia. The classic forms of 21-hydroxylase deficiency, salt-wasting (SW) and simple virilising (SV), usually present in the neonatal period with some simple virilising patients presenting later in childhood with precocious pseudopuberty. The non-classic form (NCCAH) mostly m...

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic disease. 5β-reductase (AKR1D1) is highly expressed in human liver where it inactivates steroid hormones and, in parallel, catalyzes a fundamental step in bile acid synthesis. Steroid hormones, including glucocorticoids, as well as bile acids (BAs) are established regulators of metabolic phenotype. We have hypothesized that AKR1D1 plays a crucial regulatory role in hepatic metabolic homeost...

Hyperandrogenaemia and polycystic ovary syndrome (PCOS) are common in women with Type 1 diabetes, but it is not known if they contribute to increased cardiovascular risk. We aimed to compare associations between androgen levels, lipid variables and early atherosclerosis in reproductive-age women with and without T1DM. 87 (16 with PCOS) women with T1DM (mean±SD; age 28.7±6.1yrs, BMI 25.4±4.4kg/m2), and 87 (16 PCOS) nondiabetic women (mean±SD; age ...

Background: Management of patients with CAH remains challenging. There is increasing evidence to suggest that failure to optimize treatment during childhood not only affects final height but also leads to psychological and psychiatric problems, reflecting an underlying effect on neural development. Previous qualitative structural T2-weighted MRI studies have identified white matter hyper-intensities in up to 46% of CAH patients. The nature and functional relevance of these abn...

BackgroundPolycystic Ovary Syndrome (PCOS) is the most prevalent endocrine disorder in women of reproductive age. The main components are hyperandrogenemia and oligo-/amenorrhea. The pathophysiology of PCOS is not fully understood which is why no causal treatment options are available. A multitude of observational studies demonstrated elevated C-reactive protein (CRP) levels in patients with PCOS compared with weight-matched controls. CRP is a sensitive ...