Initial laboratory evaluation to determine the cause of hyperandrogenemia in an adolescent female

17OHP: 17-hydroxyprogesterone; Beta-hCG: beta-human chorionic gonadotropin; CAH: congenital adrenal hyperplasia; DHEAS: dehydroepiandrosterone sulfate; FSH: follicle-stimulating hormone; IGF-1: insulin-like growth factor 1; LH: luteinizing hormone; NCCAH: nonclassic congenital adrenal hyperplasia; PCOM: polycystic ovary morphology; PCOS: polycystic ovary syndrome; SHBG: sex hormone-binding globulin; TSH: thyroid-stimulating hormone.

* Pregnancy is associated with elevated testosterone levels.

¶ Slightly elevated LH and slightly low FSH are common in PCOS. High FSH suggests primary hypogonadism. Low LH suggests hypogonadotropic hypogonadism.

Δ Thyroid dysfunction may alter the total testosterone level by altering SHBG. Hypothyroidism may cause multicystic ovaries and coarse hair that may be mistaken for hirsutism.

◊ Ultrasonography is generally reserved for patients with atypical features (eg, testosterone level >150 mg/dL, clitoromegaly, rapidly progressing hirsutism, poor response to treatment). Ultrasonography screens for ovarian and adrenal tumors. Ultrasound may detect ovotesticular disorder of sex development (true hermaphroditism) or hCG-related disorders of pregnancy. PCOM is supportive but is neither specific nor a diagnostic criterion for adolescent PCOS.

§ Moderate elevations of 8:00 AM 17OHP (>170 ng/dL [>5.1 nmol/L]) is approximately 95% sensitive and 90% specific for detecting the most common type of NCCAH (21-hydroxylase deficiency) in anovulatory or follicular-phase women. NCCAH is the most common condition mimicking PCOS. 17OHP elevation is often found in virilizing neoplasms.

¥ DHEAS >700 mcg/dL (>13.6 micromol/L) suggests an adrenal virilizing tumor or the rare 3-beta-hydroxysteroid dehydrogenase deficiency form of NCCAH.

‡ Hyperprolactinemia can cause anovulation either with hyperandrogenemia (usually accompanied by galactorrhea) or without hyperandrogenemia (due to hypogonadotropic hypogonadism).

† Cushing syndrome should be considered in hyperandrogenic cases with central obesity. Plasma cortisol <10 mcg/dL (<276 nmol/L) essentially rules out endogenous Cushing syndrome unless the clinical index of suspicion is high.

** Acromegaly should be ruled out by IGF-1 screening if the patient has acromegaloid overgrowth. The IGF-1 result should be interpreted in the context of the patient's age; the normal range is higher for adolescents than for adults.

¶¶ Exclusion of the preceding disorders in a hyperandrogenic patient with menstrual dysfunction meets standard diagnostic criteria for PCOS with approximately 99% reliability. However, this work-up does not identify rare adrenal disorders (eg, rare types of CAH and adrenal steroid metabolic disorders), very small tumors such as the rare testosterone-secreting neoplasm, or idiopathic hyperandrogenism. If symptoms persist, these patients should be reevaluated.