Congenital Adrenal Hyperplasia

Abstract Congenital adrenal hyperplasia (CAH) describes a family of inherited disorders whose common feature is impaired cortisol synthesis. Cortisol is produced from cholesterol in the adrenal glands through a series of enzymatic reactions. A genetic mutation of the gene encoding one of these enzymes can lead to CAH. In some forms of CAH, a build up of steroid precursors to the defective enzyme leads to an overproduction of androgens, sex steroids, causing to virilization of a female foetus affected with CAH. Most cases of CAH are owed to a defect in the enzyme, 21‐hydroxylase. This family of disorders is treatable with oral glucocorticoids. Key Concepts: Congenital adrenal hyperplasia describes a group of autosomal recessive genetic defects in the enzymes of steroidogenesis. The adrenal glands produce steroids including glucocorticoids, mineralocorticoids and sex steroids (androgens). Deficiency of 21‐hydroxylase causes more than 90% of cases of CAH and is characterised by glucocorticoid and mineralocorticoid deficiency associated with virilization in females. There are two forms of CAH: the classical form, which includes the salt‐wasting and the simple virilizing forms and the nonclassical form, which is associated with milder symptoms. The main goals of medical therapy for CAH are to replace deficient cortisol with a suitable glucocorticoid, deficient aldosterone with mineralocorticoid replacement and sodium supplements, and to prevent excessive androgen secretion. Prenatal dexamethasone treatment can prevent genital ambiguity in an affected female foetus with classical CAH. The presence of cell‐free foetal DNA in maternal plasma has opened up new possibilities for noninvasive prenatal testing of 21‐hydroxylase deficiency and other genetic steroid disorders.