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Epic Test Code LAB524 Dehydroepiandrosterone Sulfate (DHEA-S), Serum

Additional Codes

MML:DHES1


Specimen Required


Container/Tube:

Preferred: Serum gel

Acceptable: Red top

Submission Container/Tube: Plastic vial

Specimen Volume: 0.6 mL


Useful For

Diagnosis and differential diagnosis of hyperandrogenism (in conjunction with measurements of other sex steroids)

 

An adjunct in the diagnosis of congenital adrenal hyperplasia

 

Diagnosis and differential diagnosis of premature adrenarche

Method Name

Immunoenzymatic Assay

Reporting Name

Dehydroepiandrosterone Sulfate, S

Specimen Type

Serum

Specimen Minimum Volume

0.5 mL

Specimen Stability Information

Specimen Type Temperature Time
Serum Refrigerated (preferred) 14 days
  Frozen  30 days

Reject Due To

Hemolysis

Mild OK; Gross reject

Lipemia

Mild OK; Gross OK

Icterus

NA

Other

NA

Clinical Information

Dehydroepiandrosterone (DHEA) is the principal human C-19 steroid. DHEA has very low androgenic potency, but serves as the major direct or indirect precursor for most sex steroids. DHEA is secreted by the adrenal gland and production is at least partly controlled by adrenocorticotropic hormone. 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. Within weeks after birth, DHEA-S levels fall by 80% or more and remain low until the onset of adrenarche. Adrenarche is a poorly understood phenomenon peculiar to higher primates, which is characterized by a gradual rise in adrenal androgen production. It precedes puberty but is not causally linked to it. Early adrenarche is not associated with early puberty or with any reduction in final height or overt androgenization and is generally regarded as a benign condition, not needing intervention. However, girls with early adrenarche may be at increased risk of polycystic ovarian syndrome as adults, and some boys may develop early penile enlargement.

 

Following adrenarche, DHEA-S levels increase until the age of 20, up to maximum levels roughly comparable to that observed at birth. Levels then decline over the next 40 to 60 years to around 20% of peak levels. The clinical significance of this age-related drop is unknown and trials of DHEA-S replacement in the elderly have not produced convincing benefits. However, in young and old patients with primary adrenal failure, the addition of DHEA-S to corticosteroid replacement has been shown in some studies to improve mood, energy, and sex drive.

 

Elevated DHEA-S levels can cause symptoms or signs of hyperandrogenism in women. Men are usually asymptomatic, but through peripheral conversion of androgens to estrogens can occasionally experience mild estrogen excess. Most mild to moderate elevations in DHEA-S levels are idiopathic. However, pronounced elevations of DHEA-S may be indicative of androgen-producing adrenal tumors. In small children, congenital adrenal hyperplasia (CAH) due to 3 beta-hydroxysteroid deficiency is associated with excessive DHEA-S production. Lesser elevations may be observed in 21-hydroxylase deficiency (the most common form of CAH) and 11 beta-hydroxylase deficiency. By contrast, steroidogenic acute regulatory protein or 17 alpha-hydroxylase deficiencies are characterized by low DHEA-S levels.

 

An initial workup in adults might also include total and bioavailable testosterone (TTBS / Testosterone, Total and Bioavailable, Serum) measurements. Depending on results, this may be supplemented with measurements of sex hormone-binding globulin (SHBG /Sex Hormone-Binding Globulin [SHBG], Serum) and, occasionally other androgenic steroids (eg, 17-hydroxyprogesterone).

Reference Values

MALES

1-14 days: DHEA-S levels in newborns are very elevated at birth but will fall to prepubertal levels within a few days.

Tanner Stages* 

Mean

Age

Reference Range (mcg/dL)

Stage I

>14 days

11-120

Stage II

11.5 years

14-323

Stage III

13.6 years

5.5-312

Stage IV

15.1 years

29-412

Stage V

18.0 years

104-468

*Puberty onset (transition from Tanner stage I to Tanner stage II) occurs for boys at a median age of 11.5 (±) 2 years. For boys, there is no proven relationship between puberty onset and body weight or ethnic origin. Progression through Tanner stages is variable. Tanner stage V (adult) is usually reached by age 18.

18-30 years: 105-728 mcg/dL

31-40 years: 57-522 mcg/dL

41-50 years: 34-395 mcg/dL

51-60 years: 20-299mcg/dL

61-70 years: 12-227 mcg/dL

≥71 years: 6.6-162 mcg/dL

FEMALES

1-14 days: DHEA-S levels in newborns are very elevated at birth but fall to prepubertal levels within a few days.

Tanner Stages* 

Mean

Age

Reference Range (mcg/dL)

Stage I

>14 days

16-96

Stage II

10.5 years

22-184

Stage III

11.6 years

11-296

Stage IV

12.3 years

17-343

Stage V

14.5 years

57-395

*Puberty onset (transition from Tanner stage I to Tanner stage II) occurs for girls at a median age of 10.5 (±) 2 years. There is evidence that it may occur up to 1 year earlier in obese girls and in African American girls. Progression through Tanner stages is variable. Tanner stage V (adult) is usually reached by age 18.

18-30 years: 83-377 mcg/dL

31-40 years: 45-295 mcg/dL

41-50 years: 27-240 mcg/dL

51-60 years: 16-195 mcg/dL

61-70 years: 9.7-159

≥71 years: 5.3-124 mcg/dL

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), domapinergic drugs (eg, levodopa/dopamine, bromocryptine), fish oil, and vitamin E.

 

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

Cautions

There are currently no established guidelines for dehydroepiandrosterone sulfate (DHEA-S) replacement or supplementation therapy or its biochemical monitoring. In most settings, the value of DHEA-S therapy is doubtful. However, if DHEA-S therapy is used, then it seems prudent to avoid overtreatment, with its associated hyperandrogenic effects. These are particularly likely to occur in postmenopausal females if DHEA-S levels approach or exceed the upper reference range. Most supplements contain dehydroepiandrosterone (DHEA), but the in vivo conversion to DHEA-S allows monitoring of either DHEA or DHEA-S.

 

For assays employing antibodies, the possibility exists for interference by heterophile antibodies in the patient sample. Patients who have been regularly exposed to animals or have received immunotherapy or diagnostic procedures utilizing immunoglobulins or immunoglobulin fragments may produce antibodies, e.g. HAMA, that interfere with immunoassays. Additionally, other heterophile antibodies such as human antigoat antibodies may be present in patient samples (1,2) Such interfering antibodies may cause erroneous results. Carefully evaluate the results of patients suspected of having these antibodies and compare with other clinical information.

Day(s) and Time(s) Performed

Monday through Friday; 6 a.m.-12 a.m.

Saturday; 6 a.m.-6 p.m.

Analytic Time

Same day/1 day

Specimen Retention Time

14 days

Performing Laboratory

Mayo Clinic Laboratories in Rochester

CPT Code Information

82627

NY State Approved

Yes

Forms

If not ordering electronically, complete, print, and send a General Request (T239) with the specimen.