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Difficulty: HardPediatric Endocrine Disorders

Match the following clinical presentations of suspected adrenal enzyme deficiencies with their most likely underlying diagnosis. Evaluate both the mineralocorticoid status and the degree of virilization to determine the correct enzyme defect.

  • A 2-week-old 46,XX neonate presents with virilized external genitalia, failure to thrive, serum Na+Na^+ 124 mEq/L, and serum K+K^+ 6.8 mEq/L.2121-hydroxylase deficiency
  • A 2-week-old 46,XX neonate presents with virilized external genitalia, a blood pressure of 115/75 mm Hg (elevated for age), serum Na+Na^+ 145 mEq/L, and serum K+K^+ 2.9 mEq/L.11β11\beta-hydroxylase deficiency
  • A 16-year-old phenotypic female with a 46,XY karyotype presents with primary amenorrhea, absent secondary sexual characteristics, a blood pressure of 150/95 mm Hg, and serum K+K^+ 2.8 mEq/L.17α17\alpha-hydroxylase deficiency
  • A 2-week-old 46,XY neonate presents with hypospadias (undervirilized external genitalia), severe volume depletion, hyponatremia, hyperkalemia, and a markedly elevated 17-hydroxypregnenolone to 17-hydroxyprogesterone ratio.3β3\beta-hydroxysteroid dehydrogenase deficiency

Answer

The presentations match as follows: virilized/salt-wasting to 21-hydroxylase deficiency; virilized/hypertensive to 11-beta-hydroxylase deficiency; undervirilized/hypertensive to 17-alpha-hydroxylase deficiency; and undervirilized/salt-wasting (with elevated precursor ratio) to 3-beta-hydroxysteroid dehydrogenase deficiency.
Congenital adrenal hyperplasia and related DSDs encompass several distinct enzyme defects. Diagnosis relies systematically on determining the mineralocorticoid status (hypertension and hypokalemia versus hypotension and hyperkalemia) and the androgen status (virilization in 46,XX or undervirilization in 46,XY).

Step-by-Step Solution

1
Evaluate blood pressure and potassium levels to determine mineralocorticoid effect.
Hyperkalemia and hyponatremia suggest aldosterone deficiency (21-hydroxylase or 3-beta-hydroxysteroid dehydrogenase). Hypokalemia and hypertension suggest excess mineralocorticoids (11-beta-hydroxylase or 17-alpha-hydroxylase).
This establishes the horizontal pathway of the steroidogenic block.
2
Evaluate the karyotype and external genitalia to determine androgen status.
Virilization in a 46,XX neonate indicates excess androgens (21-hydroxylase or 11-beta-hydroxylase). Undervirilization in a 46,XY neonate indicates deficient potent testosterone production (17-alpha-hydroxylase or 3-beta-hydroxysteroid dehydrogenase).
This establishes the vertical pathway of the steroidogenic block.
3
Combine the findings to isolate the specific enzyme deficiency.
Matching the mineralocorticoid and androgen profiles perfectly isolates each of the four classical congenital adrenal hyperplasia variants.
Enzyme defects create distinct accumulations of upstream precursors and deficiencies of downstream products.

Key Concept

Congenital Adrenal Hyperplasia (CAH) Enzyme Deficiencies
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Topics

Pediatric Endocrine Disorders

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