Question

Difficulty: HardPediatric Endocrine Disorders

During a routine kindergarten physical, the physician notes that a 5-year-old boy has grown significantly faster than his peers. His parents report that he has developed axillary hair and adult-like body odor over the last six months. He is otherwise healthy and takes no medications. Vital signs show a blood pressure of 134/86 mm Hg134/86\text{ mm Hg} (greater than the 99th percentile for his age and height). Physical examination reveals a muscular habitus and moderate facial acne. Genitourinary examination demonstrates Tanner stage III pubic hair, an enlarged phallus, and bilateral testicular volumes of 2 mL2\text{ mL}. Radiographic imaging of the left wrist indicates a bone age of 9 years, and his serum testosterone is markedly elevated. Which of the following laboratory abnormalities is most likely to be found in this patient?

  1. Decreased plasma renin activityAnswer
  2. B
    Elevated serum aldosterone concentration
  3. C
    Elevated basal luteinizing hormone concentration
  4. D
    Elevated serum potassium concentration
  5. E
    Suppressed serum 17-hydroxyprogesterone concentration

Answer

Decreased plasma renin activity is the correct expected finding in this patient.
The correct answer is decreased plasma renin activity. This patient presents with signs of peripheral precocious puberty (advanced bone age, pubic hair, elevated testosterone, but prepubertal testicular volume of <4 mL< 4\text{ mL}) accompanied by significant hypertension. This clinical picture is highly characteristic of 11-beta-hydroxylase deficiency, the second most common form of congenital adrenal hyperplasia. The lack of 11-beta-hydroxylase prevents the conversion of 11-deoxycorticosterone to corticosterone, and 11-deoxycortisol to cortisol. The resulting decrease in cortisol removes negative feedback on the pituitary, leading to increased adrenocorticotropic hormone (ACTH) secretion. Elevated ACTH drives the accumulation of adrenal androgens (causing virilization and peripheral precocious puberty) and 11-deoxycorticosterone. Because 11-deoxycorticosterone is a potent mineralocorticoid, its massive accumulation leads to sodium retention, volume expansion, and hypertension. This volume expanded state subsequently suppresses renin production by the juxtaglomerular cells of the kidney, resulting in decreased plasma renin activity.

Step-by-Step Solution

1
Analyze the patient's presentation of precocious puberty.
The patient has advanced virilization, rapid growth, and elevated testosterone, but prepubertal testicular volume (2 mL2\text{ mL}).
This combination differentiates gonadotropin-independent (peripheral) precocious puberty (small testes due to lack of LH/FSH stimulation) from gonadotropin-dependent (central) precocious puberty (enlarged testes).
2
Integrate the vital signs with the hormonal findings.
The patient has severe hypertension alongside peripheral precocious puberty.
The combination of peripheral androgen excess and mineralocorticoid excess strongly points toward a specific congenital adrenal hyperplasia variant, namely 11-beta-hydroxylase deficiency.
3
Deduce the laboratory profile of 11-beta-hydroxylase deficiency.
The enzymatic block leads to the accumulation of 11-deoxycorticosterone.
11-deoxycorticosterone acts as a strong mineralocorticoid, causing sodium and water retention. This volume expansion inherently suppresses plasma renin activity.

Key Concept

Pathophysiology and clinical presentation of 11-beta-hydroxylase deficiency
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