Abstract
The most frequent form of congenital adrenal hyperplasia (CAH) is steroid 21-hydroxylase
deficiency, accounting for more than 90% of cases. Affected patients cannot synthesize
cortisol efficiently. Thus the adrenal cortex is stimulated by corticotropin (ACTH)
and overproduces cortisol precursors. Some precursors are diverted to sex hormone
biosynthesis, causing signs of androgen excess including ambiguous genitalia in newborn
females and rapid postnatal growth in both sexes. In the most severe “salt wasting”
form of CAH (~75% of severe or “classic” cases), concomitant aldosterone deficiency
may lead to salt wasting with consequent failure to thrive, hypovolemia, and shock.
Newborn screening minimizes delays in diagnosis, especially in males, and reduces
morbidity and mortality from adrenal crises. CAH is a recessive disorder caused by
mutations in the CYP21 (CYP21A2) gene, most of which arise from recombination between CYP21 and a nearby pseudogene, CYP21P (CYP21A1P). Phenotype is generally correlated with genotype. Classic CAH patients require chronic
glucocorticoid treatment at the lowest dose that adequately suppresses adrenal androgens
and maintains normal growth and weight gain, and most require mineralocorticoid (fludrocortisone).
Transition of care of older patients to adult physicians should be planned in advance
as a structured, ongoing process.
Keywords
CAH -
CYP21A2
- glucocorticoid - mineralocorticoid - ambiguous genitalia
