Interpretation

Elevated dehydroepiandrosterone sulfate (DHEA-S) levels indicate increased adrenal androgen production. Mild elevations in adults are usually idiopathic, but levels of 600 mcg/dL or more can suggest the presence of an androgen-secreting adrenal tumor. DHEA-S levels are elevated in more than 90% of patients with such tumors, usually well above 600 mcg/dL. This is particularly true for androgen-secreting adrenal carcinomas, as they have typically lost the ability to produce down-stream androgens, such as testosterone. By contrast, androgen-secreting adrenal adenomas may also produce excess testosterone and secrete lesser amounts of DHEA-S.

Patients with congenital adrenal hyperplasia (CAH) may show very high levels of DHEA-S, often 5- to 10-fold elevations. However, with the possible exception of 3 beta-hydroxysteroid dehydrogenase deficiency, other steroid analytes offer better diagnostic accuracy than DHEA-S measurements. Consequently, DHEA-S testing should not be used as the primary tool for CAH diagnosis. Similarly, discovering a high DHEA-S level in an infant or child with symptoms or signs of possible CAH should prompt additional testing, as should the discovery of very high DHEA-S levels in an adult. In the latter case, adrenal tumors need to be excluded and additional adrenal steroid profile testing may assist in diagnosing nonclassical CAH.

Girls below the age of 7 to 8 and boys before age 8 to 9, who present with early development of pubic hair, or, in boys, penile enlargement, may be suffering from either premature adrenarche or premature puberty or both. Measurement of DHEA-S (DHES / Dehydroepiandrosterone Sulfate [DHEA-S], Serum), dehydroepiandrosterone (DHEA_ / Dehydroepiandrosterone [DHEA], Serum), and androstenedione (ANST / Androstenedione, Serum), alongside determination of sensitive estradiol (EEST / Estradiol, Serum), testosterone and bioavailable (TTBS / Testosterone, Total and Bioavailable, Serum), or free testosterone (TGRP / Testosterone, Total and Free, Serum), sex hormone-binding globulin (SHBG / Sex Hormone-Binding Globulin [SHBG], Serum), and luteinizing hormone (LH / Luteinizing Hormone [LH], Serum)/follicle-stimulating hormone (FSH / Follicle-Stimulating Hormone [FSH], Serum) levels will allow correct diagnosis in most cases. In premature adrenarche, only the adrenal androgens, chiefly DHEA-S, will be above prepubertal levels, whereas early puberty will also show a fall in SHBG levels and variable elevations of gonadotropins and gonadal sex-steroids above the prepuberty reference range.

Levels of DHEA-S do not show significant diurnal variation.

Many drugs and hormones can result in changes in DHEA-S levels. Whether any of these secondary changes in DHEA-S levels are of clinical significance and how they should be related to the established normal reference ranges is unknown. In most cases, the drug-induced changes are not large enough to cause diagnostic confusion, but when interpreting mild abnormalities in DHEA-S levels, drug and hormone interactions should be taken into account.

Examples of drugs and hormones that can reduce DHEA-S levels include: insulin, oral contraceptive drugs, corticosteroids, central nervous system agents that induce hepatic enzymes (eg, carbamazepine, clomipramine, imipramine, phenytoin), many antilipemic drugs (eg, statins, cholestyramine), dopaminergic drugs (eg, levodopa/dopamine, bromocriptine), fish oil, and vitamin E.

Drugs that may increase DHEA-S levels include metformin, troglitazone, prolactin, many neuroleptic drugs (by indirect implication)), danazol, calcium channel blockers (eg, diltiazem, amlodipine), and nicotine.