What is the most important initial screening study for a 5-year-old girl with premature pubarche (early onset of pubic hair growth) and adult body odor, with a height at the 75th percentile and weight at the 95th percentile, and no signs of acne or clitoromegaly (enlargement of the clitoris)?

Initial Screening for Premature Pubarche in a 5-Year-Old Girl

The most important initial screening study is dehydroepiandrosterone sulfate (DHEA-S), as it is the best marker to identify premature adrenarche—the most common cause of isolated premature pubarche—and helps exclude more serious virilizing disorders.

Rationale for DHEA-S as First-Line Test

• DHEA-S is the primary biomarker for adrenarche and will be elevated in premature adrenarche, which accounts for ≥90% of premature pubarche cases 1
• In this clinical scenario with isolated pubic hair and body odor without clitoromegaly, acne, or accelerated growth velocity, premature adrenarche is the most likely diagnosis 2, 1
• DHEA-S levels above the prepubertal range (typically >40-60 μg/dL depending on age) confirm premature adrenarche 2
• The absence of clitoromegaly and acne makes virilizing disorders like congenital adrenal hyperplasia or androgen-secreting tumors less likely 3, 4

Why Other Tests Are Not First-Line

17-Hydroxyprogesterone (Option C)

• 17-hydroxyprogesterone is indicated when atypical features suggest virilizing congenital adrenal hyperplasia, such as clitoromegaly, rapid progression, or compromised height potential 3, 1
• This patient lacks these concerning features, making nonclassic CAH less likely
• 17-OHP testing with ACTH stimulation should be reserved for cases with atypical premature pubarche (genital enlargement present) or when DHEA-S is markedly elevated 3

Testosterone (Option D)

• Testosterone may be mildly elevated in premature adrenarche but is less specific than DHEA-S for distinguishing the etiology 1
• Markedly elevated testosterone would suggest exogenous exposure, tumors, or severe CAH—all unlikely given the benign examination 4

FSH (Option B)

• FSH is used to evaluate central precocious puberty, which presents with breast development (thelarche) in girls, not isolated pubarche 5
• This patient has no breast development or other signs of true puberty, making gonadotropin testing unnecessary initially 5

Clinical Algorithm for This Patient

1. Measure DHEA-S first to confirm premature adrenarche 2, 1
2. If DHEA-S is appropriately elevated for early puberty (typically 40-150 μg/dL) with normal growth velocity and no virilization, diagnose premature adrenarche and provide reassurance 2
3. If DHEA-S is markedly elevated or atypical features develop, proceed to 17-hydroxyprogesterone with ACTH stimulation testing to exclude nonclassic CAH 3
4. Monitor growth parameters and weight, as premature adrenarche is associated with obesity and insulin resistance risk 2, 1

Important Caveats

• Rule out exogenous androgen exposure by asking about household testosterone gel use or intensive diaper cream application, which can cause premature pubarche 4
• The weight at 95th percentile is significant, as obesity is commonly associated with premature adrenarche and increases peripheral conversion of DHEA-S to active androgens 2
• Height at 75th percentile with normal growth velocity is reassuring and typical for premature adrenarche, unlike virilizing disorders which cause accelerated growth 1
• Only 5-10% of premature pubarche cases are due to virilizing disorders requiring more extensive evaluation 1

Answer: A. Dehydroepiandrosterone sulphate