Congenital adrenal hyperplasia (CAH) is a family of autosomal recessive disorders.
21-Hydroxylase deficiency, in which there are mutations in CYP21A2 (the gene encoding the adrenal
21-hydroxylase enzyme), is the most common form (90%) of CAH. In classic CAH there is impaired
cortisol production with diagnostic increased levels of 17-OH
progesterone. Excess
androgen production results in
virilization and in the newborn female may cause development of ambiguous external genitalia. Three-fourths of patients with classic CAH also have
aldosterone insufficiency, which can result in
salt-wasting; in infancy this manifests as
shock,
hyponatremia and
hyperkalemia. CAH has a reported incidence of 1:10,000-1:20,000 births although there is an increased prevalence in certain ethnic groups. Nonclassic CAH (
NCCAH) is a less severe form of the disorder, in which there is 20-50% of
21-hydroxylase enzyme activity (vs. 0-5% in classic CAH) and no
salt wasting. The degree of symptoms related to
androgen excess is variable and may be progressive with age, although some individuals are asymptomatic.
NCCAH has an incidence of 1:1000-1:2000 births (0.1-0.2% prevalence) in the White population; an even higher prevalence is noted in certain ethnic groups such as Ashkenazi Jews (1-2%). As many as two-thirds of persons with
NCCAH are compound heterozygotes and carry a severe and mild mutation on different alleles. This paper discusses the genetics of
NCCAH, along with its variable phenotypic expression, and reviews the
clinical course in untreated patients, which includes rapid early childhood growth, advanced skeletal age, premature adrenarche,
acne, impaired reproductive function in both sexes and
hirsutism as well as menstrual disorders in females. Finally, it addresses treatment with
glucocorticoids vs. non treatment and other
therapies, particularly with respect to long term issues such as adult
metabolic disease including
insulin resistance,
cardiovascular disease,
metabolic syndrome, and bone mineral density.