Definition
- DHEA-S is produced by androgenic zone of the adrenal cortex. DHEA is the principal human C-19 steroid and has very low androgenic potency but serves as the major direct or indirect precursor for most sex steroids. The bulk of DHEA is secreted as a 3-sulfoconjugate (DHEA-S). Both hormones are albumin bound, but binding of DHEA-S is much tighter. In gonads and several other tissues, most notably skin, steroid sulfatases can convert DHEA-S back to DHEA, which can then be metabolized to stronger androgens and to estrogens. During pregnancy, DHEA-S and its 16-hydroxylated metabolites are secreted by the fetal adrenal gland in large quantities. They serve as precursors for placental production of the dominant pregnancy estrogen, estriol.
- Normal range: see Table 16.28.
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TABLE 16 " “28Normal Ranges of DHES-SView LargeTABLE 16 " “28Normal Ranges of DHES-S Sex Median ( ‚ µg/dL) (Central 95%) ( ‚ µg/dL) Female 170 35 " “430 Male 280 80 " “560
Use
- Indicator of adrenal cortical function, especially for differential diagnosis of virilization, and investigations of hirsutism and alopecia in women. It is also of value in the assessment of adrenarche and delayed puberty.
- Differential diagnosis of Cushing syndrome.
- Replaces 17-KS urine excretion with which it correlates; shows no significant diurnal variation, thereby providing rapid test for abnormal androgen secretion.
Interpretation
Increased In
- CAH: Markedly increased values can be suppressed by dexamethasone. Highest values occur in CAH due to deficiency of 3 Ž ²-hydroxysteroid dehydrogenase.
- Adrenal carcinoma: Markedly increased levels cannot be suppressed by dexamethasone.
- Cushing syndrome caused by bilateral adrenal hyperplasia: Shows higher values than Cushing syndrome due to benign cortical adenoma, in which values may be normal or low.
- Cushing disease (pituitary etiology): Moderate increase in hypogonadotropic hypogonadism; DHEA-S is usually normal for chronologic age and high for bone age in contrast with idiopathic delayed puberty, in which DHEA-S is low relative to chronologic age and normal relative to bone age.
- First few days of life, especially in sick or premature infants.
- Polycystic ovary syndrome: Adrenal hyperandrogenism is a fairly typical facet of this syndrome.
Decreased In
- Addison disease
- Adrenal hypoplasia
Limitations
- Extremely high levels (>700 or 800 Ž ¼g/dL) in women are suggestive of a hormone-secreting adrenal tumor. By contrast, DHEA-SO4 levels are typically normal in the presence of ovarian tumors.
- There are currently no established guidelines for DHEA-S replacement/supplementation therapy or its biochemical monitoring.
- Many drugs and hormones can result in changes in DHEA-S levels. 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/hormones that can reduce DHEA-S levels include insulin, oral contraceptive drugs, corticosteroids, CNS agents that induce hepatic enzymes (e.g., carbamazepine, clomipramine, imipramine, phenytoin), many antilipemic drugs (e.g., statins, cholestyramine), dopaminergic drugs (e.g., levodopa/dopamine, bromocriptine), fish oil, and vitamin E.
- Drugs that may increase DHEA-S levels include metformin, troglitazone, prolactin, danazol, calcium channel blockers (e.g., diltiazem, amlodipine), and nicotine.