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Dehydroepiandrosterone-sulfate (DHEA-Sulfate)
(Adrenal Androgen – Marker for Adrenal Function, Hyperandrogenism & ACTH Activity)
Synonyms
- DHEA-S (DHEAS)
- Dehydroepiandrosterone sulfate
- Dehydroisoandrosterone sulfate
- Androgen sulfate
- Adrenal androgen
Units of Measurement
- µmol/L
- µg/mL
- µg/dL
- µg/100 mL
- µg%
- µg/L
- mg/L
1 µg/dL = 0.0271 µmol/L
1 µg/mL = 1000 µg/L
mg/L = µg/mL
µg/dL = µg% = µg/100 mL
Description
DHEA-S is a sulfated steroid hormone produced almost exclusively by the adrenal cortex (zona reticularis).
It is derived from DHEA and acts as a precursor for androgens and estrogens.
Key biological features:
- Very long half-life
- Stable throughout the day (no diurnal variation)
- High concentration in serum
- Reflects overall adrenal androgen production
- Useful as a screening marker for adrenal tumors, PCOS, and congenital adrenal hyperplasia (CAH)
Physiological Role
- Precursor for testosterone & estradiol
- Important for pubarche/adrenarche
- Marker of adrenal zona reticularis function
- Involved in immune modulation and metabolism
DHEA-S is largely inactive but acts as a reservoir for peripheral conversion.
Clinical Significance
Elevated DHEA-S (Most Important)
1. Adrenal Tumors (Adenoma or Carcinoma)
- Very high levels: >700–800 µg/dL (≈ >19–22 µmol/L)
Strongly suggest: - Adrenal androgen-secreting tumor
- Especially malignant adrenal carcinoma
2. Polycystic Ovary Syndrome (PCOS)
Moderate elevation common:
- Mild ↑ DHEA-S
- Along with ↑ LH/FSH ratio, ↑ testosterone, ↑ AMH
3. Congenital Adrenal Hyperplasia (CAH)
Especially:
- 21-hydroxylase deficiency
- 3β-HSD deficiency
- 11β-hydroxylase deficiency
DHEA-S rises due to ACTH overstimulation.
4. Premature Adrenarche
- Early pubic/axillary hair
- Mild ↑ DHEA-S in children
5. Cushing’s Syndrome (ACTH-dependent)
Excess ACTH → increased adrenal androgens.
Low DHEA-S
Causes
- Adrenal insufficiency (Addison’s disease)
- ACTH deficiency (secondary/tertiary AI)
- Aging (natural decline)
- Chronic illness
- Glucocorticoid therapy (suppression of ACTH)
Symptoms
Usually mild; may contribute to:
- Fatigue
- Low libido
- Reduced wellbeing
(Non-specific and controversial.)
Reference Intervals
(Tietz 8E + Endocrine Society + Mayo + ARUP)
Strong age- and sex-dependence.
Women (µg/dL)
| Age | Reference Range |
| 18–29 | 45 – 320 |
| 30–39 | 40 – 290 |
| 40–49 | 35 – 260 |
| 50–59 | 26 – 200 |
| 60+ | 10 – 150 |
Men (µg/dL)
| Age | Reference Range |
| 18–29 | 110 – 510 |
| 30–39 | 90 – 460 |
| 40–49 | 70 – 410 |
| 50–59 | 40 – 340 |
| 60+ | 30 – 250 |
Children & Adolescents
Gradual rise at:
- Adrenarche: ~8-10 years
- Peaks at early adulthood
- Declines steadily after age 30
Clinical Thresholds
- DHEA-S >700–800 µg/dL (≈19–22 µmol/L) → suggest adrenal tumor
- Persistently high with virilization → adrenal carcinoma until ruled out
- Low DHEA-S in younger adults → suggests primary or secondary adrenal insufficiency
Diagnostic Uses
1. Evaluate Hyperandrogenism
Differentiates:
- PCOS
- Adrenal tumor
- Late-onset CAH
- Cushing disease
2. Workup of Premature Adrenarche
Mild elevation confirms early adrenal activation.
3. Diagnosis of Adrenal Tumors
High DHEA-S strongly suggests adrenal origin rather than ovarian.
4. Adrenal Insufficiency Evaluation
Low DHEA-S correlates with reduced ACTH activity.
5. Monitoring CAH Treatment
DHEA-S helps track adequacy of glucocorticoid suppression.
Analytical Notes
- No diurnal variation → sample any time
- Serum preferred
- Interference from biotin (high doses) possible
- Immunoassays commonly used; LC-MS/MS most accurate
- Oral contraceptives may reduce DHEA-S
- Pregnancy slightly lowers DHEA-S (placental metabolism)
Clinical Pearls
- DHEA-S is the most specific lab marker for adrenal androgen excess.
- Testosterone elevation with normal DHEA-S → ovarian source.
- High DHEA-S with virilization → adrenal tumor until proven otherwise.
- CAH shows high DHEA-S + high 17-OHP + high ACTH.
- Low DHEA-S in adults should prompt evaluation for adrenal insufficiency.
Interesting Fact
DHEA-S is one of the most abundant hormones in the human body by mass - tens to hundreds of times higher than testosterone or cortisol.
References
- Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Steroid Hormones.
- Endocrine Society Guidelines - Hyperandrogenism & Adrenal Disorders.
- AACE Guidelines - PCOS & CAH.
- Mayo Clinic Laboratories - DHEA-S.
- ARUP Consult - Adrenal Androgen Testing.
- MedlinePlus / NIH - DHEA-S.