Why DHEA Bloodwork is Checked
DHEA-S (dehydroepiandrosterone sulfate) bloodwork is primarily checked to evaluate adrenal androgen production when investigating hyperandrogenism, to help distinguish between adrenal versus ovarian sources of androgen excess, and to aid in diagnosing adrenal insufficiency.
Primary Clinical Indications for DHEA-S Testing
Evaluation of Hyperandrogenism
DHEA-S serves as a second-line diagnostic marker when first-line androgen tests (total testosterone, free testosterone, or free androgen index) are negative but clinical suspicion for hyperandrogenism remains high 1.
DHEA-S is measured when total testosterone is twice the upper limit of normal to help localize the source of androgen excess 2.
Markedly elevated DHEA-S levels (>600 μg/dL) strongly suggest an androgen-secreting adrenal cortical adenoma, requiring adrenal imaging with CT or MRI 2, 3.
In suspected adrenocortical carcinoma (ACC) or when clinical signs of virilization are present (clitoromegaly, voice deepening, rapid symptom onset), DHEA-S should be measured alongside other androgens 1.
Diagnostic Performance in PCOS
DHEA-S has limited utility for diagnosing PCOS, with pooled sensitivity of 0.75 and specificity of only 0.57, making it inferior to testosterone-based measurements 1.
The area under the curve (AUC) for DHEA-S in PCOS diagnosis is 0.77, lower than total testosterone (0.87), calculated free testosterone (0.85), and free androgen index (0.87) 1.
Only 8.1% of women with PCOS have elevated DHEA-S when age-adjusted norms are used, compared to 4.3% in controls 4.
DHEA-S elevation is found in approximately 20-33% of PCOS patients depending on race and phenotype, but correlates only with other androgens and not with ovarian, pituitary, or metabolic markers 1, 4.
Diagnosis of Adrenal Insufficiency
A normal age- and sex-adjusted DHEA-S level practically rules out the diagnosis of adrenal insufficiency (both primary and central) 5.
Low DHEA-S is a characteristic finding in primary adrenal insufficiency, alongside low cortisol, elevated ACTH, and low aldosterone 3.
When baseline serum cortisol is ≥12 μg/dL or DHEA-S is normal for age and sex, adrenal insufficiency is extremely unlikely 5.
Low or equivocal DHEA-S levels require dynamic testing (1-μg cosyntropin test) to definitively assess hypothalamic-pituitary-adrenal axis function 5.
Measurement Methodology Considerations
Assay Methods and Accuracy
Direct immunoassays for DHEA-S have sensitivity of 0.67 and specificity of 0.70 6, 1.
LC-MS/MS methods have higher sensitivity (0.82) but lower specificity (0.57) compared to direct immunoassays 6, 1.
The choice of assay method significantly impacts diagnostic accuracy, though the differences are less pronounced for DHEA-S than for testosterone measurements 1.
Clinical Context and Interpretation
Age-Related Considerations
DHEA-S levels decline progressively with age at approximately 2% per year, reaching maximum concentrations between ages 20-30 years 1, 7.
Age-adjusted reference ranges are essential for accurate interpretation, as failure to use age-specific norms leads to overdiagnosis of DHEA-S elevation 4.
Source Localization in Hyperandrogenism
DHEA-S is primarily of adrenal origin in women, making it useful for distinguishing adrenal from ovarian sources of androgen excess 2, 1.
Normal DHEA-S with elevated testosterone suggests ovarian hyperthecosis (often with insulin resistance) or androgen-secreting ovarian tumor 2.
DHEA-S correlates with total testosterone (r=0.34), androstenedione (r=0.24), and 17-hydroxyprogesterone (r=0.22), but not with LH, FSH, or AMH 4.
Common Clinical Pitfalls
When NOT to Rely on DHEA-S
Do not use DHEA-S as a first-line test for PCOS diagnosis due to poor specificity and low prevalence of elevation 1, 4.
DHEA-S measurement adds little value for understanding PCOS pathophysiology except when testosterone levels are very high (>2× upper limit of normal) 4, 2.
A low DHEA-S alone is insufficient to establish the diagnosis of adrenal insufficiency and requires confirmation with dynamic testing 5.
Appropriate Clinical Algorithm
For hyperandrogenism evaluation:
- First-line: Measure total testosterone and free testosterone (or FAI) by LC-MS/MS 8, 1
- Second-line: If first-line tests are negative but clinical suspicion remains high, measure DHEA-S and androstenedione 1, 8
- If DHEA-S >600 μg/dL: Obtain adrenal CT/MRI to exclude adrenal tumor 3, 2
- If testosterone >2× upper limit with normal DHEA-S: Obtain pelvic ultrasound for ovarian pathology 2, 3
For suspected adrenal insufficiency: