Congenital Adrenal Hyperplasia

Congenital adrenal hyperplasias (CAH) are autosomal recessive disorders associated with impaired function of one of the enzymes necessary for cortisol synthesis. Decreased enzyme function leads to cortisol deficiency, increased ACTH secretion via loss of negative feedback inhibition, and overproduction of the substrates before the impaired enzymatic step. Gonadal steroid synthesis may also be impaired because several of the enzymatic steps involved in cortisol biosynthesis are also required for gonadal sex hormone synthesis. Deleterious genetic variants have been identified in the steroidogenic enzyme genes. This chapter presents an overview regarding enzyme deficiencies resulting in CAH, focusing on 21-hydroxylase deficiency, which accounts for 95% of cases of CAH. These disorders manifest a clinical spectrum ranging from classic forms to milder forms. Glucocorticoid therapy remains the mainstay of CAH treatment. Newborn screening programs have enabled prompt diagnosis and treatment of CAH. Novel therapeutic agents are being scrutinized. Prenatal treatment remains experimental and is not considered a standard of care.