Review the following clinical scenarios of patients with suspected congenital adrenal hyperplasia. Match each patient's clinical presentation and laboratory profile to the most likely specific deficient adrenal enzyme.
- A 2-week-old genotypic female (46,XX) presents with virilized ambiguous genitalia, lethargy, blood pressure of 60/40 mmHg, serum sodium of 126 mEq/L, and serum potassium of 6.4 mEq/L.21-hydroxylase
- A 2-week-old genotypic female (46,XX) presents with virilized ambiguous genitalia, blood pressure of 105/65 mmHg (>95th percentile for age), serum sodium of 146 mEq/L, and serum potassium of 3.1 mEq/L.11-beta-hydroxylase
- A 16-year-old genotypic male (46,XY) presents with phenotypic female external genitalia, primary amenorrhea, absent secondary sexual characteristics, blood pressure of 142/92 mmHg, and serum potassium of 3.0 mEq/L.17-alpha-hydroxylase
Answer
The hypotensive, hyperkalemic virilized infant has 21-hydroxylase deficiency. The hypertensive, hypokalemic virilized infant has 11-beta-hydroxylase deficiency. The hypertensive, hypokalemic under-virilized adolescent has 17-alpha-hydroxylase deficiency.
The adrenal steroidogenesis pathway branches into mineralocorticoids, glucocorticoids, and androgens. A block at 21-hydroxylase eliminates mineralocorticoids and glucocorticoids, causing salt wasting and androgen excess. A block at 11-beta-hydroxylase eliminates terminal mineralocorticoids and glucocorticoids but traps 11-deoxycorticosterone (a potent mineralocorticoid), causing hypertension, hypokalemia, and androgen excess. A block at 17-alpha-hydroxylase eliminates glucocorticoids and androgens, forcing all production down the mineralocorticoid pathway, resulting in hypertension, hypokalemia, and phenotypic female genitalia regardless of genotypic sex.
Step-by-Step Solution
Key Concept
Clinical and laboratory differentiation of Congenital Adrenal Hyperplasia (CAH) enzyme deficiencies