Approach to the adult with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Abstract

Congenital adrenal hyperplasia (CAH) describes a group of autosomal recessive disorders where there is impairment of cortisol biosynthesis. CAH due to 21-hydroxylase deficiency accounts for 95% of cases and shows a wide range of clinical severity. Treatment of the classic or severe form of CAH is targeted at replacing cortisol and aldosterone and effectively controlling excess androgen symptoms by using the lowest possible glucocorticoid dose. Treatment of the mild or nonclassic form is targeted at controlling excess androgen symptoms and may or may not involve glucocorticoid therapy. Hydrocortisone is the treatment of choice for children, but there is no consensus on how patients should be treated as adults. Current glucocorticoid therapy is suboptimal because it is often difficult to reduce excess androgen without giving excess glucocorticoid, and patients may experience hypercortisolism, androgen excess, or a combination of these states. Treatment of CAH, especially in the adult patient, remains controversial given the lack of prospective randomized controlled trials comparing treatment regimens. Nevertheless, patients benefit from careful individualized therapy with avoidance of Cushingoid side effects and optimization of reproductive, sexual, and bone health.

Figure 1

Clinical management of CAH is often a balancing act between two undesirable states: hyperandrogenism and hypercortisolism. If glucocorticoid is administered so as to achieve physiological replacement or prevent adrenal insufficiency, excess adrenal androgen remains. If glucocorticoid is increased to maximize suppression of excess adrenal androgen production, iatrogenic hypercortisolism will occur.

Figure 2

Algorithm outlining the clinical considerations of patients with CAH. GC, Glucocorticoid; OC, oral contraceptive. ¹ Long-acting glucocorticoid is preferred, but hydrocortisone should be considered and might be the drug of choice in the older adult when fertility is no longer desired. ² Dexamethasone should not be used in the sexually active female without concomitant use of oral contraceptive. ³ Genetic counseling should include information regarding maternal dexamethasone for the fetus at risk for classic CAH.