When laboratory testing for the assessment of hirsutism is indicated, either a bioavailable testosterone level (includes a total testosterone, SHBG, and albumin level) or a calculated free testosterone level (if albumin levels are assumed to be normal) provides the most accurate assessment of the androgen effect derived from testosterone. In clinical situations requiring a testosterone evaluation, the addition of 17-hydroxyprogesterone will screen for adult onset adrenal hyperplasia, when indicated (Table 31.2). When hirsutism is accompanied by absent or abnormal menstrual periods, assessment of prolactin and thyroid-stimulating hormone (TSH) values are required to diagnose an ovulatory disorder. Hypothyroidism and hyperprolactinemia may result in reduced levels of SHBG and may increase the fraction of unbound testosterone levels, occasionally resulting in hirsutism. In cases of suspected Cushing syndrome, patients should undergo screening with a 24-hour urinary cortisol (most sensitive and specific) assessment or an overnight dexamethasone suppression test. For this test, the patient takes 1 mg of dexamethasone at 11 p.m., and a blood cortisol assessment is performed at 8 a.m. the next day. Cortisol levels of 2 μg/dL or higher after overnight dexamethasone suppression require a further workup for evaluation of Cushing syndrome. Elevated 17hydroxyprogesterone (17-OHP) levels identify patients who may have AOAH, found in 1% to 5% of hirsute women. The 17-OHP levels can vary significantly within the menstrual cycle, increasing in the periovulatory period and luteal phase, and may be modestly elevated in PCOS. Standardized testing requires early morning testing during the follicular phase.
According to the Endocrine Society clinical guidelines, patients with morning follicular phase 17-OHP levels of less than 300 ng/dL (10 nmol/L) are likely unaffected. When levels are greater than 300 ng/dL but less than 10,000 ng/dL (300 nmol/L), ACTH testing should be performed to distinguish between PCOS and AOAH. Levels greater than 10,000 ng/dL (300 nmol/L) are virtually diagnostic of congenital adrenal hyperplasia.
Precocious pubarche precedes the diagnosis of adult onset congenital adrenal hyperplasia in 5% to 20% of cases. Measurement of 17-OHP should be performed in patients presenting with precocious pubarche, and a subsequent ACTH stimulation test is recommended if basal 17-OHP is greater than 200 ng/dL. A study using a 200 ng/dL threshold for basal 17-OHP plasma levels to prompt ACTH stimulation testing offered 100% (95% confidence interval [CI], 69– 100) sensitivity and 99% (95% CI, 96–100) specificity for the diagnosis of adult onset congenital adrenal hyperplasia within the cohort with precocious puberty (6).
Because increased testosterone production is not reliably reﬂected by total testosterone levels, the clinician may choose to rely on typical male pattern hirsutism as confirmation of its presence, or may elect measures that reﬂect levels of free or unbound testosterone (bioavailable or calculated free testosterone levels). Total testosterone does serve as a reliable marker for testosterone-producing neoplasms. Total testosterone levels greater than 200 ng/dL should prompt a workup for ovarian or adrenal tumors.
Although the ovary is the principal source of androgen excess in most of PCOS patients, 20% to 30% of patients with PCOS will demonstrate supranormal levels of DHEAS. Measuring circulating levels of DHEAS has limited diagnostic value, and overinterpretation of DHEAS levels should be avoided (7).