Comparison of Two Forms of Hydrocortisone in Patients With Congenital Adrenal Hyperplasia

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a disease of the adrenal cortex characterized by cortisol deficiency with or without aldosterone deficiency, and androgen excess. The severe or classic form occurs in 1 in 15,000 births worldwide, while the mild non-classic form is a common cause of hyperandrogenism. The discovery of glucocorticoid therapy as a treatment for CAH occurred in the 1950's resulting in patients with classic CAH surviving to live a normal lifespan. However, existing treatment is suboptimal and many unresolved clinical problems exist. Standard hormone replacement often fails to normalize the growth and development of children with CAH, and adults may experience iatrogenic Cushing syndrome, hyperandrogenism, infertility or the development of the metabolic syndrome. Chronocort, a newly-developed formulation of hydrocortisone, results in a slow release of hydrocortisone that is designed to mimic the normal cortisol circadian rhythm. This new medical strategy, physiologic cortisol replacement, offers the prospect of an improved outcome of treatment. Chronocort has been safely given to healthy adult males in pharmacokinetic studies. This first ever study in patients with CAH is a pharmacokinetic/pharmacodynamic study comparing Chronocort to Cortef, the conventional immediate-release form of hydrocortisone.