In the various forms of congenital adrenal hyperplasia, production of cortisol (a glucocorticoid), aldosterone (a mineralocorticoid), or both is impaired because of an autosomal recessive genetic defect in one of the adrenal enzymes involved in synthesizing adrenal steroid hormones from cholesterol. The enzyme may be absent or deficient, completely or partially disabling synthesis of cortisol, aldosterone, or both. In the forms in which cortisol synthesis is absent or decreased, adrenocorticotropic hormone (ACTH, corticotropin) release, normally suppressed by cortisol, is excessive.
The most common forms of congenital adrenal hyperplasia are 21-hydroxylase deficiency and 11beta-hydroxylase deficiency. In these forms, precursors proximal to the enzyme block accumulate and are shunted into adrenal androgens. The consequent excess androgen secretion causes varying degrees of virilization in external genitals of affected females; no defects are discernible in external genitals of males.
In some less common forms affecting enzymes other than 21-hydroxylase and 11beta-hydroxylase, the enzyme block impairs androgen synthesis (dehydroepiandrosterone [DHEA] or androstenedione). As a result, virilization of males is inadequate, but no defect is discernible in females.