How to diagnose Polycystic Ovary Syndrome (PCOS) with elevated Dehydroepiandrosterone (DHEA) levels while ruling out Congenital Adrenal Hyperplasia (CAH)?

Diagnosing PCOS with Elevated DHEA While Ruling Out CAH

To diagnose PCOS in a patient with elevated DHEAS levels, first measure total testosterone (TT) and free testosterone (FT) by LC-MS/MS, then perform a 17-hydroxyprogesterone test to rule out CAH before confirming PCOS diagnosis. 1

Diagnostic Algorithm for PCOS vs CAH

Step 1: First-Line Laboratory Testing

• Total Testosterone (TT) - Measure using LC-MS/MS (sensitivity 0.74, specificity 0.86) 2
• Free Testosterone (FT) - Either measured by equilibrium dialysis or calculated using Free Androgen Index (FAI) (sensitivity 0.89, specificity 0.83) 2, 1
• Sex Hormone Binding Globulin (SHBG) - Required for calculating FAI 2

Step 2: Rule Out CAH

• 17α-hydroxyprogesterone (17-OHP) - Critical test to differentiate PCOS from non-classic congenital adrenal hyperplasia (NCAH) 2, 3
  • Perform in early morning (follicular phase)
  • If 17-OHP is elevated (>200 ng/dL), consider ACTH stimulation test to confirm or rule out CAH

Step 3: Additional Testing for Hyperandrogenism

• DHEAS levels - Elevated in 20-30% of PCOS patients 4, 5
  • Less specific than TT or FT (sensitivity 0.75, specificity 0.67) 2
  • More commonly elevated in non-classic PCOS phenotypes (B and C) 6
• Androstenedione (A4) - Consider if clinical suspicion remains high but TT/FT not conclusive 2, 1

Step 4: Clinical Assessment

• Document hyperandrogenic symptoms:
  • Hirsutism (using modified Ferriman-Gallwey score)
  • Acne
  • Androgenic alopecia
  • Menstrual irregularities 2, 1

Step 5: Confirm PCOS Diagnosis

• Rotterdam criteria (requires 2 of 3):
  1. Clinical or biochemical hyperandrogenism
  2. Oligo/anovulation
  3. Polycystic ovaries on ultrasound 2

Interpreting Elevated DHEAS in PCOS vs CAH

• PCOS with elevated DHEAS:

  • 17-OHP levels normal or mildly elevated but <200 ng/dL
  • DHEAS elevation is part of generalized androgen excess 6
  • Often seen in lean PCOS phenotypes 7
  • Represents adrenal contribution to overall hyperandrogenism 5

• CAH presentation:

  • Significantly elevated 17-OHP (>200 ng/dL)
  • More pronounced elevation after ACTH stimulation
  • May have similar clinical features to PCOS (hirsutism, menstrual irregularity)
  • Often presents with earlier onset of symptoms 2

Additional Considerations

• Laboratory timing: Morning collection is preferred for androgen measurements 1
• Assay method matters: LC-MS/MS is strongly preferred over immunoassay methods for all androgen measurements due to superior accuracy 2, 1
• Age considerations: DHEAS levels are age-dependent and decrease by approximately 40% from twenties to thirties 6
• BMI impact: DHEAS levels tend to be higher in lean-PCOS compared to obese-PCOS patients 7

Common Pitfalls to Avoid

1. Relying solely on DHEAS: While elevated in many PCOS patients, DHEAS alone has lower diagnostic accuracy (AUC 0.77) compared to TT (AUC 0.87) or FAI (AUC 0.87) 2

2. Using direct immunoassays: These methods have lower accuracy compared to LC-MS/MS, particularly at the lower concentrations seen in women 2, 1

3. Failing to rule out CAH: Always measure 17-OHP to exclude non-classic CAH, as treatments differ 2, 3

4. Ignoring clinical correlation: Biochemical markers should be interpreted alongside clinical signs - positive correlations exist between hirsutism score and FAI, cFT, and cBT 3

By following this systematic approach, clinicians can accurately diagnose PCOS with elevated DHEAS while properly excluding CAH, leading to appropriate treatment strategies that will improve morbidity, mortality, and quality of life outcomes.