Congenital adrenal hyperplasia

Congenital adrenal hyperplasia is not one disease but a group of them. All of them are inherited in an autosomal recessive pattern, meaning that both copies of the gene have to be altered for the condition to appear, and all of them affect one of the enzymes the adrenal gland uses to build steroid hormones out of cholesterol. The enzymes are the tools on that assembly line.

If a tool is missing, cortisol, the hormone of stress and metabolism, does not come out right. The body notices, and the pituitary, a small gland at the base of the brain, insists: it sends more corticotropin, the hormone that tells the adrenal gland to produce cortisol. Because the order is never filled, the order never stops, and the adrenal cortex, the outer layer of the gland, gets larger. That is the hyperplasia in the name. The factory cannot make what is being ordered, gets told to work harder and grows, but overproduces something else: cortisol precursors build up and the pathway shunts toward androgens, the masculinizing hormones, or toward mineralocorticoid precursors.

Many enzymes can be involved, but one dominates the picture: 21-hydroxylase deficiency. Defects in the gene that makes it, CYP21A2, account for about ninety-five percent of cases.