CAH Definition, Aetiology, DDx

Definition
Congenital adrenal hyperplasia is (CAH) a genetic disorder characterized by a deficiency in the hormones cortisol and aldosterone.

Aka adrenogenital syndrome; 21-hydroxylase deficiency.

Aetiology
CAH is an autosomal recessive disorder; both sexes are affected with equal frequency.

Homozygous patients are affected with CAH. Heterozygotes are asymptomatic carriers.

Many of the genes involved in cortisol and aldosterone synthesis code for CYP proteins. The best-studied gene is the 21-hydroxylase gene (CYP21, CYP21B). The 21-hydroxylase gene is located on the short arm of chromosome 6 among genes that code for proteins determining human leukocyte antigen (HLA) types (controlling immune function).

Various mutations of the 21-hydroxylase gene result in various degrees of CAH (salt-losing form, simple-virilizing form, and the nonclassic form).

Clinical presentation

Types	Name	Female symptoms	Male symptoms
Severe CYP21, CYP11B1, partial 3-beta-hydroxysteroid dehydrogenase deficiency	Female: Classic virilizing adrenal hyperplasia/ Classic salt-wasting adrenal hyperplasia	Ambiguous genitalia at birth due to excess adrenal androgen production in utero	Normal genitalia at birth; present at 1-4 weeks because of FTT, recurrent vomiting, dehydration, hypotension, hyponatremia, hyperkalemia, shock
Mild 21-hydroxylase deficiency	Simple virilizing adrenal hyperplasia	Present later in childhood; precocious pubic hair, clitoromegaly, or both often accompanied by accelerated growth and skeletal development due to excess postnatal exposure to adrenal androgens	Present later in childhood; early development of pubic hair, phallic enlargement, or both accompanied by accelerated linear growth and advancement of skeletal maturation
Milder deficiencies of 21-hydroxylase or 3-beta-hydroxysteroid dehydrogenase activity	Nonclassic adrenal hyperplasia	Present in adolescence or adulthood; oligomenorrhea, hirsutism, and/or infertility
Steroidogenic acute regulatory (StAR) deficiency, classic 3-beta-hydroxysteroid dehydrogenase deficiency, or CYP17 deficiency		Phenotypically female at birth but does not develop breasts or menstruate in adolescence because of inadequate estradiol production	Ambiguous genitalia or female genitalia due to inadequate testosterone production in the first trimester of fetal life

Differential Diagnosis
Ambiguous genitalia
Possible causes in genetic females

• Congenital adrenal hyperplasia (CAH). Certain forms of this genetic condition cause the adrenal glands to make excess male hormones (androgens). Congenital adrenal hyperplasia is the most common cause of ambiguous genitalia in newborns.
• Ingestion by the mother of substances with male hormone activity, such as progesterone (taken in the early stages of pregnancy to stop bleeding).
• Tumors in the fetus or the mother that produce male hormones.

Possible causes in genetic males

• Impaired testicle development due to genetic abnormalities or unknown causes.
• Leydig cell aplasia, a condition that impairs testosterone production.
• Congenital adrenal hyperplasia. Certain forms of this genetic condition can impair production of male hormones.
• Androgen insensitivity syndrome, a condition in which developing genital tissues are unable to respond to normal male hormone levels.
• 5 alpha reductase deficiency, an enzyme defect that impairs normal male hormone production.
• Ingestion by the mother of substances with female hormone activity, such as estrogens, or anti-androgens. This is unusual, but could occur if a woman taking birth control pills gets pregnant despite taking the pills — then, not knowing she's pregnant, continues taking the pills into pregnancy for several weeks. Also some "nutritional supplements" contain plant estrogens.

Vomiting
In infants,

• Serious infection (eg, sepsis, meningitis)
• Gastroesophageal reflux
• Obstructive GI disorders such as pyloric stenosis or bowel obstruction (eg, from duodenal stenosis or volvulus) - a constriction in the outlet from the stomach
• Neurologic conditions (eg, meningitis, tumor or other space-occupying lesion)
• Metabolic disorders (eg, adrenogenital syndrome, galactosemia)

In older children, vomiting often results from acute gastroenteritis or appendicitis.

Lethargy/sleepiness
Dehydration

Sources:
http://www.emedicine.com/ped/topic48.htm
www.caresfoundation.org
http://www.merck.com/mmpe/sec19/ch266/ch266l.html