Endocrine Abstracts

CAH is the commonest inborn endocrine disorder and associated with significant morbidity. The health status of CAH adult patients has recently been reported by the UK Congenital adrenal Hyperplasia Adult Study Executive, CaHASE (Arlt et al. JCEM 2010 95 5110–5121). Compared to the health survey for England, metabolic abnormalities were common in adult patients with CAH: obesity (41%), hypercholesterolemia (46%), insulin resistance (29%), osteopenia (40%), and osteoporosis (7%). HR-QOL (SF-36) showed significant impairment similar to scores in heart failure. The CAH patients were taking different glucocorticoid therapies at various doses (n=196): hydrocortisone (n=25M, 26W), prednisolone (n=21M, 67W), dexamethasone (n=15M, 22W), or combination therapy (n=4M, 16W). The CaHASE group have hypothesised that steroid dose mediates some adverse metabolic outcomes. ANOVA and univariate regression analysis only showed weak correlations (r<0.2) between prednisolone equivalent dose and SBP and DBP, HDL-cholesterol and HOMA-IR. However, using principal component analysis (PCA), it was identified that disease control factors, BP and mutation severity are associated with both the choice and total dose of glucocorticoid prescribed. Studies, independent of CaHASE, have examined the development of a modified release formulation of hydrocortisone, Chronocort, for the treatment of adults with CAH. Chronocort, in dexamethasone suppressed normal individuals, is capable of recreating the physiological rise in overnight cortisol levels and in adult patients with CAH improved control of morning 17-hydroxyprogesterone compared to immediate release hydrocortisone. In conclusion, health status in adults with CAH is significantly impaired and Chronocort represents a foundation for future drug development in the pursuit of physiological cortisol replacement.

CaHASE is grateful to the Society for Endocrinology for management of the project and The Clinical Endocrinology Trust for financial support.