Congenital adrenal hyperplasia caused by 21-hydroxylase deficiency

[Britney]

21-Hydroxylase (CYP21A2) deficiency causes defective conversion of adrenal precursors to cortisol and, in some cases, to aldosterone, sometimes resulting in severe hyponatremia and hyperkalemia. Accumulated hormone precursors are shunted into androgen production, causing virilization. Diagnosis is by measurement of cortisol, its precursors, and adrenal androgens, sometimes after adrenocorticotropic hormone administration. Treatment is with a glucocorticoid plus, if needed, a mineralocorticoid and, for some female neonates with genital ambiguity, surgical reconstruction.
21-Hydroxylase deficiency causes 90% of all cases of congenital adrenal hyperplasia. Incidence ranges from 1/10,000 to 1/15,000 live births. Disease severity depends on the specific CYP21A2 mutation and degree of enzyme deficiency. The deficiency completely or partially blocks conversion of 17-hydroxyprogesterone to 11-deoxycortisol, a precursor of cortisol, and conversion of progesterone to deoxycorticosterone, a precursor of aldosterone. Because cortisol synthesis is decreased, adrenocorticotropic hormone (ACTH) levels increase, which stimulates the adrenal cortex, causing accumulation of cortisol precursors (eg, 17-hydroxyprogesterone) and excessive production of the adrenal androgens dehydroepiandrosterone (DHEA) and androstenedione. Aldosterone deficiency can lead to salt wasting, hyponatremia, and hyperkalemia (1, 2).