What is the DHEAS (dehydroepiandrosterone sulfate) lab test used for and when is it clinically relevant?

DHEAS Laboratory Testing: Clinical Uses and Relevance

DHEAS is a second-line diagnostic test for hyperandrogenism, used only when first-line testosterone measurements (total and free testosterone) are normal but clinical suspicion remains high, and serves as a marker to identify adrenal sources of androgen excess. 1, 2

Primary Clinical Indications

When to Order DHEAS:

• Second-line testing for hyperandrogenism when total testosterone and free testosterone measured by LC-MS/MS are not elevated but clinical signs persist (hirsutism, acne, androgenic alopecia, oligomenorrhea) 1, 2
• Evaluating adrenal androgen production when clinical signs of virilization are present alongside other androgens 1, 2
• Screening for adrenal tumors when DHEAS levels exceed 600 μg/dL, which raises concern for adrenocortical carcinoma 1
• Diagnosing congenital adrenal hyperplasia (CAH), particularly nonclassic forms, though ACTH stimulation testing is more definitive 3

Diagnostic Performance and Limitations

Poor Specificity for PCOS:

• DHEAS has inferior diagnostic accuracy compared to testosterone-based measurements, with pooled sensitivity of 75% but specificity of only 57-67% for PCOS diagnosis 4, 2
• The area under the curve (AUC) is 0.77 for DHEAS versus 0.87 for total testosterone, 0.85 for calculated free testosterone, and 0.87 for free androgen index 4, 2
• Only 8-33% of PCOS patients have elevated DHEAS levels, making it unreliable as a first-line marker 1

Assay Method Considerations:

• Direct immunoassays show sensitivity of 67% and specificity of 70% 2, 5
• LC-MS/MS methods have higher sensitivity (82%) but paradoxically lower specificity (57%) 2, 5
• Standardization problems exist across commercial immunoassays, with some showing slopes ranging from 0.84 to 1.28 compared to reference methods 6

Critical Interpretation Factors

Age-Adjusted Reference Ranges Are Mandatory:

• DHEAS levels peak between ages 20-30 years and decline approximately 2% per year thereafter 1, 2
• Failure to use age-specific norms leads to overdiagnosis of DHEAS elevation 1, 2
• Prevalence of elevated DHEAS in PCOS varies by ethnicity: approximately 20% in White patients and 33% in Black patients when age-adjusted values are used 1

Common Clinical Pitfalls

Do Not Use DHEAS as First-Line Testing:

• The Endocrine Society and American College of Obstetricians and Gynecologists explicitly recommend against using DHEAS as a first-line test for PCOS due to poor specificity 1, 2
• First-line testing should always be total testosterone and free testosterone by LC-MS/MS 1, 2

Limitations in Monitoring CAH Treatment:

• DHEAS is disproportionately suppressed in treated CAH patients, even when other markers suggest adequate control 7, 8
• Measurement of DHEAS has limited value in assessing adequacy of therapy in 21-hydroxylase deficiency 7
• Blunted adrenarche occurs in classical CAH patients, with DHEAS levels typically in the lower part of normal range regardless of disease control 8

Poor Correlation with Other Androgens:

• Basal DHEAS levels do not correlate with hormonal response to ACTH stimulation 3
• 61% of hirsute women with subtle adrenal steroidogenesis defects had normal DHEAS levels 3
• Basal DHEAS measurements may be misleading and are not helpful in differentiating causes of androgen excess 3

Practical Diagnostic Algorithm

Step 1: Measure total testosterone and free testosterone by LC-MS/MS in the morning (first-line) 1, 2

Step 2: If testosterone levels are normal but clinical suspicion remains high (persistent hirsutism, acne, virilization), then measure DHEAS and androstenedione as second-line tests 1, 2

Step 3: If DHEAS >600 μg/dL, evaluate for adrenal tumor with imaging 1

Step 4: If DHEAS is mildly elevated with clinical signs, consider ACTH stimulation testing to evaluate for nonclassic CAH rather than relying on DHEAS alone 3

When DHEAS Is NOT Clinically Useful

• Monitoring treatment response in CAH due to disproportionate suppression 7, 8
• First-line diagnosis of PCOS due to low sensitivity (only elevated in 8-33% of cases) 1
• Predicting response to ACTH stimulation as basal levels do not correlate with dynamic testing 3
• Establishing adrenal insufficiency as low DHEAS alone is insufficient without confirmatory dynamic testing 2