Evaluation of isolated premature pubarche

SD: standard deviations; DHEAS: dehydroepiandrosterone sulfate; 17-OHP: 17-hydroxyprogesterone; ACTH: adrenocorticotropic hormone (cosyntropin); CAH: congenital adrenal hyperplasia; DHEA: dehydroepiandrosterone; LH: luteinizing hormone; FSH: follicle-stimulating hormone; PAPSS2: 3'-phospho-adenosine 5'-phosphosulfate [PAPS] synthase.
* Occasionally, body odor or acne is the presenting complaint rather than premature pubarche.
¶ Other secondary sex characteristics refer to breast development in girls or testicular enlargement in boys. Children with these characteristics or with accelerated growth velocity should be evaluated for precocious puberty (refer to UpToDate content on precocious puberty).
Δ Exogenous androgen exposure may be due to use of an androgen-containing cream, gel or spray, or oral anabolic body-building supplement by a caregiver. These androgens may be transferred to the child by skin-to-skin contact or inadvertent ingestion.
◊ Practice varies regarding laboratory testing. Some experts perform a laboratory evaluation (DHEAS with or without 17-OHP, A and T) during the initial evaluation for precocious pubarche, at the same time as the bone age determination. Other experts perform the laboratory evaluation only for children whose bone age is advanced for chronologic age; and still others perform laboratory testing for those whose bone age is advanced for their height age (eg, predicted adult height subnormal for the family height and/or bone age ≥120% of their height age), provided that there are no additional signs of virilization.
§ 17-OHP should be tested in the early morning (8 AM); a normal 17-OHP value in an afternoon blood sample does not exclude CAH. If there is any evidence of breast development or testicular enlargement, LH and FSH levels should also be measured to assess for central precocious puberty.
¥ Premature adrenarche is a provisional diagnosis; these patients should be followed clinically. If the child develops any signs of virilization, pubertal progression, or accelerated growth velocity, further evaluation is warranted, including bone age determination and the panel of laboratory tests described above.
‡ In premature adrenarche, DHEAS is generally between 40 and 115 mcg/dL, but should also be appropriate for pubic hair stage. Children with DHEAS <40 mcg/dL and normal results for other laboratory tests probably have idiopathic premature pubarche. Evaluation for an androgen-secreting tumor (eg, with a dexamethasone suppression test) is warranted for children with marked elevations in DHEAS (eg, >5 times the age-specific upper limit of normal) or testosterone (eg, >2 times the age-specific upper limit of normal), or those with rapid clinical progression and advanced bone age.
† In children with premature adrenarche, 17-OHP is usually normal (<115 ng/dL), but occasionally is mildly elevated (115 to 200 ng/dL). Children with mildly elevated 17-OHP concentrations should be followed clinically. If virilization develops (clitoromegaly in girls, or penile enlargement in boys) or linear growth/bone age accelerate, further evaluation should be performed. This may include repeating basal laboratory tests, an ACTH stimulation test to evaluate for CAH and/or a dexamethasone suppression test to evaluate for an androgen-secreting tumor.
** 17-OHP >1000 ng/dL with or without ACTH stimulation is diagnostic of CAH due to 21-hydroxylase deficiency. Molecular genetic testing may be helpful to confirm the diagnosis and for genetic counseling purposes.
¶¶ The combination of elevated androstenedione, testosterone and DHEA with low DHEAS suggests a PAPSS2 mutation, a rare disorder in which conversion of DHEA to DHEAS is impaired. DHEAS concentrations may be normal or slightly elevated in individuals with CAH due to 21-hydroxylase deficiency.