Further evaluation for a child with premature pubarche and suspicion for Cushing disease or hyperandrogenic disorder

DHEAS: dehydroepiandrosterone sulfate; CAH: congenital adrenal hyperplasia; ULN: upper limit of normal; ACTH: adrenocorticotropic hormone.
* Laboratory findings raising concern for an androgen (C19 steroid)-secreting tumor include DHEAS >5 times the age-specific ULN and/or androstenedione or testosterone >2 times the age-specific ULN.
¶ A dexamethasone suppression test is used to distinguish between Cushing syndrome and androgen-secreting tumors^[1-3]. Other screening tests for adrenal hypercortisolemia include 24-hour urinary free cortisol excretion and midnight salivary cortisol concentration. Imaging should be performed only after confirmation of endogenous excessive glucocorticoid and/or androgen production.
Δ Refer to UpToDate content on Cushing syndrome. Cushing syndrome may be ACTH dependent (eg, due to pituitary hypersecretion of ACTH, also known as Cushing disease) or ACTH independent (eg, due to exogenous glucocorticoid administration or primary adrenal hyperfunction from an adrenal adenoma). Another rare cause of elevated morning cortisol is familial glucocorticoid resistance (eg, due to NR3C1 variants), which is not associated with Cushingoid features (refer to UpToDate content on premature adrenarche).
◊ Evaluate for gonadal androgen-secreting tumors. For girls, pelvic ultrasound is appropriate (transvaginal pelvic ultrasound should not be used in this age group). For boys, scrotal ultrasound is appropriate.
§ Consider rare disorders associated with excessive androgen (C19 steroid) secretion or metabolism such as cortisone reductase deficiency, apparent cortisone reductase deficiency, apparent DHEA sulfotransferase deficiency, familial male-limited precocious puberty, and portosystemic shunting. Evaluation to distinguish among these causes is discussed in UpToDate content on premature adrenarche and uncommon CAHs.