21-HYDROXYLASE-DEFICIENT NONCLASSIC ADRENAL-HYPERPLASIA

Inherited adrenal enzymatic deficiencies causing hyperandrogenic sympt oms some time after birth are defined as nonclassical adrenal hyperpla sia (NC-CAH). While 21-hydroxylase (21-OH) deficiency accounts for the vast majority of NC-CAH, deficiencies in 11 beta hydroxylase and 3 be ta-hydroxysteroid dehydrogenase may rarely result in the disorder. End ocrinologically evident 21-OH-deficient NC-CAH appears to affect betwe en 1% and 10% of hyperandrogenic women. Clinically evident deficiencie s of 21-OH result from mutations of the CYP21 gene. The Leu-281 mutati on is present in approximately 60%, Ser-453 in 25%, and Pro-30 in 10% of NC-CAH patients. Androgenic symptoms in NC-CAH generally appear per ipubertally, frequently coinciding with adrenarche. The clinical prese ntation, which is usually mild, cannot be used to distinguish 21-OH de ficient NC-CAH patients from other hyperandrogenic patients, The hormo nal profile is also nondiagnostic, with the exception of the basal fol licular phase 17-hydroxyprogesterone (17-HP) level. In untreated patie nts a 17-HP level of less than or equal to 2 ng/mL (6.0 nmol/L) effect ively rules out NC-CAH. Alternatively, 20% of hyperandrogenic patients demonstrating a 17-HP level of >2 ng/mL (>6.0 nmol/L) have NC-CAH. En do crinologically, NC-CAH is diagnosed by a 17-HP level 30 to 60 minut es after the acute IV administration of ACTH-[1-24] exceeding 10 ng/mL (30.3 nmol/L), and more frequently, 15 ng/mL (45.4 nmol/L). In NC-CAH ovulatory function responds well to glucocorticoids and/or clomiphene citrate, although many patients with NC CAH become pregnant without r equiring treatment. Hirsute NC-CAH generally require the addition of a nti androgen therapy to their glucocorticoid therapy.