Congenital adrenal hyperplasia in Infant/Neonate
CAH can be classified into 2 main clinical presentations: classic salt-wasting and nonclassic. The clinical presentation of classic CAH is directly related to the amount of residual enzyme activity and can range from simple virilizing (previously called non-salt-wasting) to a life-threatening adrenal crisis.
There are multiple genetic enzyme defects that can lead to CAH. These include 21-hydroxylase deficiency, 11-beta-hydroxylase deficiency, 17-alpha-hydroxylase deficiency, 3-beta-hydroxysteroid dehydrogenase deficiency, P450 oxidoreductase deficiency, and congenital lipoid adrenal hyperplasia.
21-hydroxylase deficiency accounts for 95% of all cases of CAH and is inherited in an autosomal recessive pattern. It is due to a mutation of the CYP21 gene. Different genetic mutations result in varying degrees of enzyme activity, which correlate with the severity of clinical symptoms and presentation. CAH due to 21-hydroxylase deficiency can occur in a classic or nonclassic form. The incidence of the classic form is roughly 1:15 000, while that of the nonclassic form is approximately 1:100. Classic CAH due to 21-hydroxylase deficiency can be further divided into a salt-wasting form (75%) and a simple virilizing form (25%). 21-hydroxylase is necessary for the production of cortisol and aldosterone. Lack of this enzyme shunts intermediate steroid precursors toward androgen production. Symptoms are related to excess androgens and, in the salt-wasting form of classic CAH, decreased aldosterone. Aldosterone is necessary for normal sodium retention and potassium secretion by the kidney.
E25.0 – Congenital adrenogenital disorders associated with enzyme deficiency
237751000 – Congenital adrenal hyperplasia
Differential Diagnosis & Pitfalls
- Polycystic ovarian syndrome can present with hirsutism, acne, and menstrual irregularities, but these patients will not have increased serum 17-hydroxyprogesterone, classical electrolyte abnormalities (hyponatremia, hyperkalemia), or increased urine 17-ketosteroids.
- 5-alpha-reductase deficiency can cause ambiguous genitalia in male neonates because of a lack of conversion of testosterone to the more physiologically active dihydrotestosterone. At puberty, these patients may partially virilize.
- Androgen insensitivity syndrome can cause ambiguous genitalia in male neonates, but prenatal undervirilization occurs with absence of pubic and axillary hair and lack of acne.
- Adrenal hemorrhage