Congenital adrenal hyperplasia (CAH) is a family of inborn errors of steroidogenesis, each disorder characterized by a specific enzyme deficiency that impairs cortisol production by the adrenal cortex. Numerous investigators have unraveled the mechanisms of adrenal steroid synthesis and the associated enzyme defects responsible for the clinical syndromes. The enzyme most often deficient is 21-hydroxylase, the focus of this seminar, which accounts for over 90% of CAH cases, and is the most common cause of genital ambiguity in the newborn. Less often, CAH is caused by deficiencies of 11β-hydroxylase, 3β-hydroxysteroid dehydrogenase, aldosterone synthase, 17α-hydroxylase/17,20-lyase, and the steroidogenic acute regulatory protein (lipoid hyperplasia).

Correctly identifying the form of CAH is achieved by the observation of clinical syndromes reflecting distinct hormonal patterns, and is measured quantitatively as abnormally low or high glucocorticoid, mineralocorticoid, and androgen levels. In the severe, or classical form of CAH owing to 21-hydroxylase deficiency (21-OHD), adrenal androgen overproduction causes prenatal virilization in females and continued masculinization postnatally in both sexes. There are two types of classical CAH, including simple virilizing and salt-wasting. The less severe, nonclassical form of 21-hydroxylase deficiency does not cause genital ambiguity in females and is characterized by signs of postnatal androgen excess. Approximately 60 mutations in the gene for 21-hydroxylase, CYP21, have been identified to cause classical and nonclassical CAH. These identifications have important implications for early prenatal diagnosis and prenatal treatment. The current direction of CAH research is focusing on improved therapeutic management of patients, including promising new treatment protocols, as well as exploring the possibility of gene therapy.