A 47-day-old newborn has ambiguous genitalia. Serum sodium concentration is 120 mEq/L and serum potassium concentration is 7 mEq/L. Chromosome analysis shows a 46,XX karyotype. This infant most likely has a defect in the synthesis of which of the following hormones?

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Quizplus · Accepted Answer

The infant's symptoms and lab findings suggest congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, leading to decreased cortisol synthesis. This results in ambiguous genitalia, hyponatremia, and hyperkalemia due to salt-wasting.  CYP21A2 (21-hydroxylase) deficiency is the most common enzyme defect in the adrenal gland. In one form of the disorder, called the "salt-wasting" form, aldosterone synthesis is impaired. The lack of 21-hydroxylase leads to a decrease of cortisol synthesis. This is due to the fact that 17α-hydroxyprogesterone cannot be converted to 11-deoxycortisol, the precursor of cortisol. By feedback regulation, low serum cortisol concentration results in increased production of ACTH. Increased ACTH leads to adrenal gland hyperstimulation and increased production of adrenal androgens, which results in precocious puberty. Females with this form of the disease present at birth due to ambiguity in the external genitalia.

A 47-Day-Old Newborn Has Ambiguous Genitalia