Endocrine Abstracts

The prevalence of metabolic syndrome and its hepatic manifestation, non-alcoholic fatty liver disease (NAFLD), continues to escalate. Glucocorticoids (GCs) and bile acids (BAs) are established regulators of metabolic phenotype. 5β-reductase (AKR1D1) is highly expressed in human and rodent liver, where it inactivates steroid hormones and catalyses a fundamental step in BA synthesis. We have previously demonstrated that AKR1D1 modulates hepatic GC availability and GC recept...

Introduction: Worldwide the Short Synacthen Test (SST) is the most popular investigation for adrenal insufficiency (AI). Its invasivity make it resource-intensive. Salivary cortisol is a well-established alternative to serum. We have developed a non-invasive alternative to the SST, using a novel formulation of Synacthen (containing a drug enhancer, chitosan) administered nasally and utilising saliva to measure glucocorticoid response.Methods: Four open-l...

Suppression of excess androgen production poses a considerable clinical challenge in the management of patients with congenital adrenal hyperplasia (CAH). Whilst the major route of androgen synthesis in humans is the classic pathway via androstenedione and testosterone, the relative contribution of the alternative pathway originating from 17-hydroxyprogesterone to androgen excess in CAH has not been defined. Androgen effects of both pathways are elicited in androgen target tis...

Background: Treatment of CAH in childhood focuses on growth and development; however the impact of final height (FH) on adult health is not known. We examined the relationship between FH, adiposity, cardiometabolic risk and quality of life (QoL) in a cohort of adult patients.Methods: Cross-sectional analysis of 199 adults with CAH. FH, waist circumference (WC) and QoL were expressed as z-scores adjusted for mid-parental target height (FHTH<...

Background: Quality of life (QoL) has been variously reported as normal or impaired in congenital adrenal hyperplasia (CAH) adults. We found impaired QoL in UK CAH adults and now report the relationship between QoL, glucocorticoid treatment and health outcomes in these patients.Methods: Cross-sectional analysis of 151 CAH adults with 21-hydroxylase deficiency aged 18–69 years in whom QoL (SF-36), glucocorticoid regimen, anthropometric, and metabolic...

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-...

Context11-oxygenated C19 steroids have recently gained attention as markers of androgen control in congenital adrenal hyperplasia (CAH) due to 21hydroxylase deficiency (21OHD). However, they have not yet been systematically investigated in the context of different glucocorticoid (GC) replacement regimens and in particular not in patients receiving new modified-release formulations.MethodsCross-sectional singl...

BackgroundStandard glucocorticoid (GC) therapy in classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-OHD-CAH) is often inadequate in controlling adrenal androgen excess, leading to GC over-exposure and poor health outcomes. A novel modified-release formulation of hydrocortisone (MR-HC, Chronocort® Diurnal Ltd. UK) has been shown to improve circulating adrenal androgen excess in 21-OHD-CAH. We investigated whether saliva and ...

Introduction: First-line treatment for congenital adrenal hyperplasia (CAH) is hydrocortisone1. When adequate control is not achieved, prednisolone (or its prodrug prednisone) are often used. However, there has been no formal comparison of disease control in CAH comparing prednis(ol)one vs hydrocortisone and patients are often on a glucocorticoid dose that exceeds the guideline recommended dose of hydrocortisone (≤25 mg/day)1,2. We report an interim...

Background: Congenital adrenal hyperplasia (CAH) is a rare condition that is associated with life long risk of adrenal crisis. Management of CAH demands a fine balance between excess glucocorticoid leading to adverse effects and too little glucocorticoid risking adrenal crises. Frequent occurrence of sick day episodes warrants dose adjustment and education regarding adrenal crisis. In a condition such as CAH it is difficult to collect sufficient data from small cohorts at a si...