Abstract

A deficiency of 21-hydroxylase in the adrenal cortex results in insufficient cortisol production. The salt-wasting form of 21-hydroxylase deficiency is characterized by inadequate aldosterone production, as well. Because the hypothalamic-adrenal negative feedback system is broken, excess adrenal androgens are produced. This disordered corticosteroid production causes hormonal and clinical symptoms, including pseudohermaphroditism in genetic females and disordered puberty in both males and females. There is a spectrum of the time of onset and the severity of these symptoms. This disorder is inherited in an autosomal recessive manner. The 21-hydroxylase deficiency is genetically linked to the human leukocyte antigen (HLA) complex; in addition, nonclassical and classical 21-hydroxylase deficiency have each been shown to be in genetic linkage disequilibrium with specific HLA-B antigens. This genetic linkage, used in conjunction with baseline and stimulated serum hormonal levels, is useful in the diagnosis of this disorder. Prenatal diagnosis of homozygote, heterozygote, and unaffected fetuses is also available. Adequate treatment with glucocorticoid and mineralocorticoid replacement resolves symptoms and enables a normal life.