Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders resulting from deficiency of one of the enzymes required for synthesis of cortisol in the adrenal cortex. The most common form of the disease is classic 21-hydroxylase deficiency, which is characterized by decreased synthesis of glucocorticoids and often mineralocorticoids, adrenal hyperandrogenism and impaired development and function of the adrenal medulla. The clinical management of classic 21-hydroxylase deficiency is often suboptimal, and patients are at risk of developing in tandem iatrogenic hypercortisolism and/or hyperandogenism. Limitations of current medical therapy include inability to control hyperandrogenism without employing supraphysiologic doses of glucocorticoid, hyperresponsiveness of the hypertrophied adrenal glands to ACTH and difficulty in suppressing ACTH secretion from the anterior pituitary. Current therapy with immediate-release hydrocortisone is most commonly used for glucocorticoid replacement in patients with classic 21-hydroxylase deficiency. However, conventional hydrocortisone treatment cannot simulate the physiologic rhythm of cortisol secretion. Optimization of current treatment has been attempted with thrice-daily dosing, which still fails to simulate the normal diurnal rhythm of cortisol secretion and results in temporary over- or under-replacement. Proof-of-concept studies using hydrocortisone infusions predict improvement in biochemical control and quality of life. Delayed and sustained release oral formulations of hydrocortisone are being developed, and these represent a novel treatment approach that offers the prospect of physiologic cortisol replacement. Other therapeutic alternatives that might be used in conjunction with substitution therapy include GnRH analogs, anti-androgens and aromatase inhibitors, however, many of these agents still require further evaluation in patients with the classic form of the disease.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology