Diagnosis and management of congenital adrenal hyperplasia

Congenital adrenal hyperplasia is a family of inborn errors of steroidogenesis, each characterized by a specific enzyme deficiency that impairs cortisol production by the adrenal cortex, and can lead to sexual ambiguity in both genetic males and females. The enzymes most often affected are 21-hydroxylase, 11β-hydroxylase, and 3β-hydroxysteroid dehydrogenase, and less often, 17α-hydroxylase/17, 20-lyase and cholesterol desmolase. Decreased production of cortisol results in increased pituitary secretion of adrenocorticotropic hormone. The elevated adrenocorticotropic hormone stimulates both the accumulation of precursor steroids in the impeded pathways and excessive steroid synthesis in other adrenal biosynthetic pathways unaffected by the enzyme deficiency. Correct identification of the enzyme affected is achieved by the observation of clinical syndromes reflecting distinct hormonal patterns, and it is measured quantitatively as low levels of cortisol and other adrenal steroids, as well as increased levels of steroids proximal to the blocked step. Many of the corresponding genes for the described enzymes have been isolated and characterized, and specific mutations causing many cases of congenital adrenal hyperplasia have been identified. These advances have important implications for early prenatal diagnosis and prenatal treatment.