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Difficulty: Very hardPediatric Endocrine Disorders

A 16-year-old girl, who recently immigrated from a region with limited access to pediatric healthcare, is brought to the clinic for evaluation of primary amenorrhea and severe, progressive facial hair growth. Her mother notes that she has had a deep voice and experienced a rapid growth spurt during early childhood. Her blood pressure is 162/100 mm Hg, and her pulse is 78/min. Physical examination reveals severe nodulocystic acne, temporal hair thinning, and Tanner stage 5 pubic hair development, but Tanner stage 1 breast development. Pelvic examination demonstrates significant clitoromegaly and partial fusion of the labioscrotal folds. A transabdominal pelvic ultrasound confirms the presence of a uterus and bilateral ovaries. Laboratory testing shows a serum sodium of 146 mEq/L and a serum potassium of 2.8 mEq/L. Which of the following serum laboratory profiles (17-hydroxyprogesterone, 11-deoxycorticosterone, and plasma renin activity) is most likely present in this patient?

  1. 17-hydroxyprogesterone: Elevated; 11-deoxycorticosterone: Elevated; Plasma renin activity: DecreasedAnswer
  2. B
    17-hydroxyprogesterone: Elevated; 11-deoxycorticosterone: Decreased; Plasma renin activity: Elevated
  3. C
    17-hydroxyprogesterone: Decreased; 11-deoxycorticosterone: Elevated; Plasma renin activity: Decreased
  4. D
    17-hydroxyprogesterone: Normal; 11-deoxycorticosterone: Normal; Plasma renin activity: Normal
  5. E
    17-hydroxyprogesterone: Elevated; 11-deoxycorticosterone: Elevated; Plasma renin activity: Elevated

Answer

17-hydroxyprogesterone: Elevated; 11-deoxycorticosterone: Elevated; Plasma renin activity: Decreased
The correct answer identifies the laboratory profile of 11-beta-hydroxylase deficiency. This patient's presentation of severe virilization, primary amenorrhea, and ambiguous genitalia (partial fusion of the labioscrotal folds) in the presence of a uterus indicates profound prenatal and postnatal androgen excess. The concurrent finding of hypertension and hypokalemia points to excess mineralocorticoid activity. In the adrenal steroidogenesis pathway, 11-beta-hydroxylase converts 11-deoxycorticosterone (DOC) to corticosterone and 11-deoxycortisol to cortisol. A deficiency in this enzyme leads to decreased cortisol, which removes negative feedback on the pituitary, causing increased ACTH secretion. This drives the overproduction of precursors proximal to the block. Consequently, 17-hydroxyprogesterone (17-OHP) is significantly elevated and shunted into the androgen synthesis pathway, causing virilization. Simultaneously, the direct precursor DOC is markedly elevated. DOC possesses intrinsic mineralocorticoid activity, leading to sodium retention, potassium wasting, and hypertension. This resulting volume expansion suppresses the juxtaglomerular apparatus, leading to decreased plasma renin activity.

Step-by-Step Solution

1
Analyze the patient's clinical presentation and vital signs.
The patient has severe virilization (deep voice, clitoromegaly, labioscrotal fusion), primary amenorrhea with a uterus present, hypertension (162/100 mm Hg), and hypokalemia (2.8 mEq/L).
Identifying the combination of prenatal/postnatal androgen excess and mineralocorticoid excess is crucial for narrowing down the differential diagnosis of congenital adrenal hyperplasia (CAH) variants.
2
Determine the specific enzymatic defect responsible for this presentation.
The clinical picture strongly indicates 11-beta-hydroxylase deficiency.
21-hydroxylase deficiency causes androgen excess but salt-wasting (hypotension). 17-alpha-hydroxylase deficiency causes mineralocorticoid excess (hypertension) but lack of androgens (no virilization). 11-beta-hydroxylase deficiency is the only CAH variant causing both severe virilization and hypertension.
3
Deduce the laboratory profile by tracing the interrupted steroidogenesis pathway.
17-hydroxyprogesterone is elevated, 11-deoxycorticosterone (DOC) is elevated, and plasma renin activity is decreased.
The enzyme block prevents the conversion of DOC to corticosterone, causing DOC to accumulate and act as a weak mineralocorticoid, which suppresses renin. Upstream precursors like 17-OHP also accumulate and are subsequently shunted into the active androgen synthesis pathway.

Key Concept

11-beta-hydroxylase deficiency causes congenital adrenal hyperplasia characterized by virilization (due to androgen excess) and hypertension with hypokalemia (due to the accumulation of 11-deoxycorticosterone, a weak mineralocorticoid that suppresses renin).
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Topics

Pediatric Endocrine Disorders

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