A 1-month-old infant had ambiguous genitalia at birth. The mother had not taken any medication during her pregnancy, and there was no family history of adrenogenital syndrome. Physical examination showed that the labioscrotal folds were enlarged and slightly hyperpigmented. The clitoris was also enlarged. The gonads were not palpable.
The infant's blood pressure was 85/45 mm Hg; her pulse was 120 beats per minute. Her chromosomal pattern was 46XX. At 3 days of age, her serum 17a-hydroxyprogesterone level was 19 nmol/L (normal levels are less than 8 nmol/L). Electrolyte values were normal until 6 days of age, when the serum sodium level dropped to 125 mmol/L and the serum potassium level rose to 7.2 mmol/L. A diagnosis of congenital adrenal hyperplasia was made. The child was treated with cortisone acetate, 9a-fluorocortisol, and salt supplements.
Congenital adrenal hyperplasia is an autosomal recessive disorder. Deficiency of 21-hydroxylase accounts for 95% of all cases. There are two steroid 21-hydroxylase genes (CYP21A and CYP21B). The CYP21B gene is the active gene. The CYP21A gene is 98% homologous to the CYP21B gene but is a pseudogene. Most mutations that cause 21-hydroxylase deficiency are recombinations (deletions or gene conversions) between the active CYP21B gene and the adjacent CYP21A pseudogene.
The 21-hydroxylase enzyme hydroxylates progesterone and 17a-hydroxyprogesterone to yield 11-deoxycorticosterone and 11-deoxycortisol. Deficiency of the enzyme therefore results in a deficiency of glucocorticoid and mineralocorticoid and overproduction of androgens. Most affected infants are salt-losers and have signs of virilization, as illustrated in this case. Serum levels of 17a-hydroxyprogesterone are markedly elevated and are very helpful in diagnosis.
The administration of glucocorticoid inhibits excessive production of androgens. Salt-losers should be treated with a mineralocorticoid and sodium supplements in addition to the glucocorticoid.
Increased doses are indicated during periods of stress, such as when the patient has an infection or is undergoing surgery, or during periods of decreased salt intake. The enlarged clitoris usually requires surgical correction, ideally when the child is between 6 and 12 months of age.