Clinical Scenario:
A term newborn with female-appearing external genitalia is found to have marked clitoromegaly and posterior labial fusion. At 12 days of life, she develops vomiting, poor feeding and lethargy. Investigations show Na⁺ 126 mmol/L, K⁺ 6.5 mmol/L and low cortisol. Plasma renin activity is markedly elevated. A markedly elevated 17-hydroxyprogesterone is detected. Pelvic ultrasound demonstrates a uterus.
Which of the following best explains the genital phenotype and biochemical abnormalities?
A. Maternal androgen exposure
B. Androgen insensitivity syndrome
C. 21-hydroxylase deficiency
D. 11β-hydroxylase deficiency
E. 17α-hydroxylase deficiency
Correct answer & Explanation:
Explanation
Correct answer: C. 21-hydroxylase deficiency
The newborn has virilization + salt-wasting adrenal crisis + ↑17-hydroxyprogesterone, which strongly indicates classic salt-wasting 21-hydroxylase deficiency. Reduced cortisol and aldosterone synthesis causes ↑ACTH and adrenal androgen excess, while aldosterone deficiency causes hyponatremia, hyperkalemia, dehydration and elevated renin.
Why the others are wrong:
- A. Maternal androgen exposure: Can cause virilization of a 46,XX fetus, but does not cause neonatal salt wasting, hyperkalemia or adrenal insufficiency.
- B. Androgen insensitivity syndrome: Occurs in a 46,XY infant; Müllerian structures are absent and adrenal function is normal.
- D. 11β-hydroxylase deficiency: Causes androgen excess but typically hypertension due to accumulation of deoxycorticosterone, not salt-wasting hypotension.
- E. 17α-hydroxylase deficiency: Causes hypertension with low sex-steroid production, so fetal virilization would not occur.
Exam clue:
Virilized newborn girl + salt wasting + ↑17-OHP → 21-hydroxylase deficiency.
