Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a rare form of adrenal insufficiency with a prevalence of 1 in 16,000, characterized by impaired cortisol synthesis leading to excessive adrenal androgen production. The currently recommended oral hydrocortisone (HC) therapy for children with CAH is unsatisfactory because it results in alternating hypo- and hypercortisolemia, both of which have serious long-term effects. Current oral therapy is suboptimal due to resulting non-physiologic levels of cortisol and the inability to replicate circadian and ultradian cortisol secretion rhythms associated with normal adrenal function. Therefore, an improved and personalized drug delivery system is needed which more closely replicates physiological pulsatile cortisol secretion and limits periods of hyper- and hypocortisolemia in children with a resulting tighter control of adrenal androgens.
These researchers seek to more closely replicate normal cortisol physiology by conducting the first clinical trial in children with CAH of a pulsatile SQ hydrocortisone (SQHC) pump delivery system. An open-label, non-randomized crossover design will be used for this proof-of-concept study to inform the design of a larger clinical trial. The long term goal is to improve clinical outcomes in children with CAH by optimizing the dosing and scheduling of replacement therapy and avoid the hyperandrogenemia that is specific to CAH. This study's objective is to demonstrate that pulsatile SQHC pump delivery more closely replicates circadian and ultradian rhythms of cortisol and improves control of adrenal androgens. The study's rationale is that cortisol profiles more consistent with physiologic rhythms of cortisol secretion will produce better health outcomes.