A 4-year-old boy is brought to the clinic after his mother noticed he was developing pubic hair. The boy had a recent growth spurt and is now taller than his 5-year-old brother. The patient's preschool teacher recently mentioned he has body odor after he runs or plays. Height is at the 95th percentile for age, and weight is at the 80th percentile. Examination reveals sparse growth of long, pigmented hair at the base of the penis and in both axillae. Testes are present bilaterally and appear normal. Laboratory assessment reveals high serum concentrations of 17-hydroxyprogesterone and testosterone.Which of the following is most likely present in this patient?

Question

A 4-year-old boy is brought to the clinic after his mother noticed he was developing pubic hair.  The boy had a recent growth spurt and is now taller than his 5-year-old brother.  The patient's preschool teacher recently mentioned he has body odor after he runs or plays.  Height is at the 95th percentile for age, and weight is at the 80th percentile.  Examination reveals sparse growth of long, pigmented hair at the base of the penis and in both axillae.  Testes are present bilaterally and appear normal.  Laboratory assessment reveals high serum concentrations of 17-hydroxyprogesterone and testosterone.Which of the following is most likely present in this patient?

Quizplus · Accepted Answer

11ec160b_390d_8015_9249_7f5657dbe531_MD0001_00 Deficiency of 21-hydroxylase is the most common form of congenital adrenal hyperplasia and leads to impaired conversion of 17-hydroxyprogesterone (17-OHP) to 11-deoxycortisol. Excess 17-OHP is shunted away from cortisol synthesis toward androgen production. ACTH increases due to the decline in cortisol levels and has a trophic effect on adrenal cortical cells, causing adrenal cortical hyperplasia. Depending on the residual enzyme activity, 21-hydroxylase deficiency can present as 3 distinct clinical syndromes of differing severity. This patient most likely has the classic, non-salt-wasting (ie, simple virilizing) form of the disease. Because 21-hydroxylase is not completely absent (as in the most severe form), sufficient mineralocorticoids and glucocorticoids are maintained to avoid salt wasting such that patients have normal blood pressure and electrolytes. Due to adrenal androgen overproduction, girls with this variant are often identified at birth due to ambiguous genitalia. Boys appear normal at birth and typically present around age 2-4 with early virilization (eg, body odor, pubic/axillary hair). Exposure to high levels of sex hormones also induces an early pubertal growth spurt that manifests as accelerated linear growth at a young age. In all forms of 21-hydroxylase deficiency, patients have increased 17-OHP and androgen levels. Adrenal androgens (eg, dehydroepiandrosterone and androstenedione) undergo peripheral conversion to testosterone, which explains this patient's high testosterone level. (Choice B) Adrenal medullary hyperplasia is a precursor lesion for pheochromocytoma characterized by increased catecholamine production. Presenting signs include hypertension, tachycardia, and sweating (not virilization). (Choice C) Leydig cell tumors produce excess testosterone and can present with precocious puberty in young boys (eg, early testicular/phallic enlargement). A testicular mass is typically palpated on examination. (Choice D) Production of excess LH and FSH by pituitary adenomas can lead to increased testosterone but not increased 17-OHP levels. Pituitary adenomas producing excess ACTH can lead to excess adrenal androgen production; however, symptoms of excess cortisol production (Cushing syndrome) such as growth deceleration and weight gain would predominate. (Choice E) A seminoma is a testicular tumor most commonly found in adolescents and adults. These tumors are derived from the seminiferous tubules and present with a testicular mass, not virilization and elevated testosterone. Educational objective: Deficiency of 21-hydroxylase causes adrenal cortical hyperplasia due to excess stimulation of the adrenal cortex by ACTH. The classic, non-salt-wasting form presents in boys age 2-4 with early virilization, accelerated linear growth, and elevated levels of 17-hydroxyprogesterone and androgens.

A 4-Year-Old Boy Is Brought to the Clinic After His