Congenital adrenal hyperplasia (CAH) is the term for all the disorders in which a genetic defect affects steroidogenesis, the production of steroid hormones in the adrenal gland. The condition is inherited in an autosomal recessive pattern, so a child is affected only when both copies of the responsible gene carry a defect, and each parent of an affected child is usually an unaffected carrier.
The name follows the mechanism. In the zona fasciculata, the layer of the adrenal cortex that makes glucocorticoids, production is governed by 5 different enzymatic steps. A mutation or deficiency in any of these enzymes leads to deficient production of glucocorticoids in the adrenal gland. The low level of glucocorticoids removes the negative feedback on the pituitary gland, so ACTH production rises. This over-production of ACTH has a proliferative effect on the adrenal gland, which causes hyperplasia of both glands.
More than 90% of the cases of CAH have a mutation in the 21-hydroxylase enzyme, and this form is called 21-hydroxylase deficiency (21OHD) CAH. In 21OHD CAH there is accumulation of 17-hydroxyprogesterone, the substrate of 21-hydroxylase in the glucocorticoid pathway, which can be shunted to the androgen production pathways. Regarding its epidemiology, it is estimated that there are 1:13,000 to 1:15,000 cases.
The second most common form of CAH is related to a mutation in the 11β-hydroxylase enzyme, which makes 5-8% of all the cases of CAH. 11β-OHD CAH happens in 1:100,000 live births.