Key Points
ÎÎCongenital adrenal hyperplasia (CAH) is a group of autosomal recessive
disorders characterized by impaired cortisol synthesis. In most populations
the incidence ranges from 1:10,000 to 1:20,000 births.
ÎÎThe cortisol synthetic block leads to corticotropin stimulation of the adrenal
cortex with accumulation of cortisol precursors that are diverted to sex
hormone biosynthesis.
ÎÎA cardinal feature of classic or severe virilizing CAH in newborn females is
genital ambiguity. If the disorder is not recognized and treated, both girls
and boys undergo rapid postnatal growth and sexual precocity or, in the
case of severe enzyme deficiency, neonatal salt loss and death.
ÎÎThere is a mild nonclassic form of CAH, with less severe degrees of
postnatal androgen excess; some affected individuals are asymptomatic.
ÎÎThe mild subclinical impairment of cortisol synthesis in nonclassic CAH
(NCCAH) generally does not lead to Addisonian crises.
ÎÎNonclassic forms of CAH are more prevalent.
Diagnosis and Assessment of Disease
Newborn Screening
ÎÎIncorporate screening for 21-hydroxylase deficiency into all newborn
screening programs (1|⊕⊕) using a two-tier protocol (initial
immunoassay with further evaluation of positive tests by liquid
chromatography/tandem mass spectrometry).
ÎÎStandardize first-tier screening tests to a common technology with a single
consistent set of norms stratified by gestational age (1|⊕⊕).
ÎÎFollow infants with positive newborn screens for CAH according to specific
regional protocols (1|⊕⊕).
Diagnosis of NCCAH/CAH after Infancy
ÎÎIn symptomatic individuals, obtain an early morning baseline serum
17-hydroxyprogesterone (17-OHP) (1|⊕⊕).
ÎÎObtain a complete adrenocortical profile following a cosyntropin stimulation
test to differentiate 21-hydroxylase deficiency from other enzyme defects,
and to make the diagnosis in borderline cases (1|⊕⊕).
ÎÎGenotype only when results of the adrenocortical profile following
cosyntropin stimulation test are equivocal or for purposes of genetic
counseling (2|⊕).
ÎÎConfirm adult NCCAH screening with an early morning serum measurement
of 17-OHP and when needed through an adrenocorticotropic hormone
(ACTH) stimulation test (1|⊕⊕).
