Androgen Excess Workup

Updated: Mar 14, 2018
  • Author: Mohamed Yahya Abdel-Rahman, MD, MSc; Chief Editor: Richard Scott Lucidi, MD, FACOG  more...
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Workup

Laboratory Studies

Laboratory evaluation should be part of the workup for every woman who seeks treatment for signs or symptoms of androgen excess, such as hirsutism. Although the most common cause of androgen excess in women is PCOS, some women with only mild hirsutism are found to have an androgen-secreting neoplasm, for which early diagnosis and treatment can be life saving. Furthermore, delay in diagnosis and appropriate treatment of non-life-threatening conditions can result in irreversible virilization. Fortunately, the basic laboratory evaluation for hirsutism is relatively inexpensive.

Some organizations recommend laboratory evaluation (and imaging studies) only for women with moderate or severe hirsutism (mFG >15). [62] Exceptions are made for Asian women, hirsutism of sudden onset, and the presence of other symptoms suggesting underlying pathology. However, for the reasons mentioned above, a basic laboratory evaluation can be justified in all women seeking treatment for hirsutism. [63, 64] A 2012 position statement from the Androgen Excess and Polycystic Ovary Syndrome Society recommends basic hormonal evaluations for every woman who presents with hirsutism. [65]

Laboratory tests can be divided into basic screening tests, and diagnostic tests indicated for signs and symptoms suggestive of specific pathology. [64] The following screening tests should be performed in all women presenting with signs of increased androgens.

Total testosterone

Total testosterone levels are often mildly elevated in women with PCOS, so values between the upper limit of the normal range and 2 ng/dL (2 ng/mL, 8.92 nmol/L) can be consistent with PCOS. Total testosterone levels >2 ng/dL (2 ng/mL, 8.92 nmol/L) suggest a virilizing ovarian tumor [66] or hyperthecosis.

Dehydroepiandrosterone sulphate (DHEAS)

DHEAS is secreted exclusively by the adrenal glands and is therefore a good marker for adrenal androgen production. A mildly elevated DHEAS level is common in women with PCOS. [67] In contrast, DHEAS values above 700 ng/dL (7µg/ml, 18umol/L) are suggestive of adrenal neoplasm. [68]

17-hydroxyprogesterone

Measuring serum levels of 17-hydroxyprogesterone is a screening test for nonclassic congenital adrenal hyperplasia. [69] Enzyme defects (most commonly 21-hydroxylase) result in increased levels of 17-hydroxyprogesterone. Women with levels > 200 ng/dL (6.05 nmol/L) should be further evaluated with a corticotrophin stimulation test.

Thyroid-stimulating hormone

Hypothyroidism and hyperthyroidism should be evaluated in women with androgen excess. Subclinical thyroid dysfunction may be the cause of anovulation and menstrual irregularities. Thyroid-stimulating hormone (TSH) is the screening test of choice, particularly in patients with irregular cycles. [68]

Prolactin

Hyperprolactinemia has been shown to be associated with androgen excess. Prolactin can be elevated in women with hypothyroidism. When prolactin levels are elevated in women with normal thyroid function, magnetic resonance imaging (MRI) of the pituitary may be warranted to exclude pituitary tumors.

Other diagnostic tests

Patients with signs or symptoms suggestive of specific diagnoses should undergo more extensive testing. These tests are listed below, under Other Tests.

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Imaging Studies

Ultrasonography

Analogous to laboratory evaluation, some organizations recommend imaging studies only for women with moderate or severe hirsutism (mFG >15), [62] However, many clinicians recommend pelvic ultrasonography for all women seeking treatment for signs of increased androgens since this technology is noninvasive, relatively inexpensive, and very accurate for diagnosing both PCOS and ovarian neoplasms. [64]

The diagnosis of PCOS is made in women with hirsutism when at least 1 ovary is found to have 12 or more follicles < 10 mm in diameter, assuming other pathology is excluded. [27] The presence of a large, complex ovarian cyst can indicate the presence of an androgen-secreting ovarian tumor. [70]

CT scan and MRI

Adrenal pathology is suggested by significantly elevated DHEAS levels or abnormal 24-hour urine free cortisol. Women suspected of having an adrenal neoplasm should be further evaluated with either computerized tomography (CT) or MRI. Both techniques can usually differentiate between benign adenomas and malignant nodules of the adrenal gland. [71] CT can diagnose an adrenal nodule of less than 5 mm, whereas MRI can determine if a tumor has invaded into the blood vessels. [58]

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Other Tests

Tests in addition to routine screening tests should be obtained in patients with signs or symptoms suggestive of specific diagnoses.

Oral glucose tolerance test (OGTT) and glycosylated hemoglobin

Women diagnosed with PCOS should be periodically screened for glucose intolerance and diabetes mellitus. [27, 72, 73, 74] Traditionally, a 2-hour OGTT has been recommended for both initial and periodic screening. More recently, the American Diabetic Association has recommended measuring hemoglobin A1c for diagnosing type 2 diabetes mellitus in the general population. [75, 76, 77]

24-hour urine free cortisol

Women with clinical evidence of Cushing syndrome (moon face, buffalo hump, obesity, hypertension, and dyslipidemia) should be evaluated by measuring 24-hour urine free cortisol. This test has a sensitivity >95% and specificity of 98% for diagnosing Cushing syndrome and is more specific than the dexamethasone suppression test. [78, 55]

Synthetic ACTH (corticotrophin) stimulation test

The corticotrophin stimulation test is a diagnostic test for nonclassic congenital adrenal hyperplasia when levels of 17-hydroxyprogesterone are < 200 ng/dL (6.05 nmol/L). [69] For this test, 17-hydroxyprogesterone is measured 1 hour after injection of synthetic corticotrophin. levels >10 ng/dL (30.02 nmol/L) are diagnostic for nonclassic adrenal hyperplasia.

Dexamethasone suppression, 2-day test

This test can be used to determine the source of significantly elevated androgens. After drawing baseline DHEAS, testosterone, and cortisol, the patient is give 8 doses of 0.5 mg of dexamethasone over a period of 48 hours and these tests are redrawn. An adrenal source is suggested if testosterone is suppressed more than 40% and DHEAS is suppressed more than 60%. An ovarian source is suggested if testosterone is not suppressed while DHEAS and cortisol are both suppressed. A combined source is suggested if DHEAS and cortisol are suppressed and testosterone is suppressed less than 40%. If DHEAS is not suppressed, Cushing syndrome or adrenal cancer must be considered.

GnRH analog suppression

A GnRH agonist (eg, leuprolide acetate) can be given by injection to confirm the ovarian origin of significant hyperandrogenemia when no obvious ovarian neoplasm can be found by ultrasonography. [79] The goal is to downregulate the pituitary to eliminate ovarian stimulation by FSH and LH. A GnRH agonist must be given for >2 weeks to attain this effect. More recently, GnRH agonists have become available that suppress ovarian function within days. Dexamethasone can be given as described above to suppress any contribution of the adrenal glands.

Normally, FSH, LH, estradiol, and testosterone are extremely low after suppression with a GnRH analog and dexamethasone. Inability to suppress some or all of these suggests a hormone secreting tumor.

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Procedures

Ovarian and adrenal vein sampling

Ovarian and adrenal vein sampling is used when laboratory values indicate a tumor but no tumor can be identified by imaging studies. Sampling of blood from the ovarian and adrenal veins helps determine the source of elevated androgen levels and whether 1 or both glands are involved. Involvement of a single gland is highly suggestive of a tumor. [39]

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