What laboratory tests should be ordered for a 27-year-old female presenting with hirsutism?

Laboratory Evaluation for Hirsutism in a 27-Year-Old Female

The initial laboratory workup for a 27-year-old female with hirsutism should include total testosterone, free testosterone or bioavailable testosterone, SHBG, TSH, prolactin, and a two-hour oral glucose tolerance test to evaluate for PCOS, which is the most common cause of hirsutism in reproductive-age women. 1

Initial Laboratory Assessment

First-Line Tests:

• Androgen Panel:

  • Total testosterone (preferably measured by LC-MS/MS or immunoassay after extraction) 1
  • Free testosterone or bioavailable testosterone (calculated free testosterone has high sensitivity of 89%) 1
  • Sex hormone-binding globulin (SHBG) 1
  • Free Androgen Index (FAI) 1

• Metabolic Evaluation:

  • Fasting glucose 1
  • Two-hour oral glucose tolerance test (75g glucose load) 1
  • Fasting insulin 1
  • Lipid profile (total cholesterol, LDL, HDL, triglycerides) 1

• Other Endocrine Tests:

  • Thyroid-stimulating hormone (TSH) 1
  • Prolactin 1

Second-Line Tests (Based on Clinical Suspicion):

• If severe hirsutism, rapid onset, or very high testosterone (>150 ng/dL or 5.2 nmol/L):

  • Dehydroepiandrosterone sulfate (DHEAS) 1, 2
  • Androstenedione 1
  • 17-hydroxyprogesterone (to rule out non-classic congenital adrenal hyperplasia) 1
  • Dexamethasone suppression test (if Cushing's syndrome suspected) 2

• If menstrual irregularities present:

  • LH and FSH levels (LH:FSH ratio >2 suggests PCOS) 3
  • Consider pelvic ultrasound to evaluate for polycystic ovarian morphology 3

Clinical Context for Laboratory Interpretation

When evaluating hirsutism, consider:

1. Timing of blood sampling:

   • Hormonal tests are ideally performed in the early follicular phase (days 3-6) of the menstrual cycle 3
   • Early morning sampling is preferred for testosterone measurement 2

2. Assay quality matters:

   • LC-MS/MS methods for testosterone measurement offer superior specificity (92%) compared to direct immunoassays (78%) 1
   • Calculated free testosterone has higher sensitivity (89%) than total testosterone (74%) 1

3. Clinical correlation:

   • Use the modified Ferriman-Gallwey score to objectively assess hirsutism severity (score ≥8 indicates hirsutism) 4
   • Document onset, progression, and distribution of hair growth
   • Note other signs of hyperandrogenism (acne, balding, clitoromegaly) 1
   • Assess for signs of insulin resistance (obesity, acanthosis nigricans) 1

Common Diagnostic Pitfalls

• Relying solely on total testosterone: Free testosterone or FAI may be elevated even when total testosterone is normal due to decreased SHBG levels 2
• Missing non-PCOS causes: Cushing's syndrome, androgen-secreting tumors, and non-classic congenital adrenal hyperplasia can present similarly to PCOS 1
• Overlooking metabolic assessment: PCOS patients have increased risk for type 2 diabetes and cardiovascular disease, making metabolic screening essential 1
• Inadequate sampling: Androgen levels are pulsatile; single measurements may miss subtle hyperandrogenic states 2

By following this systematic laboratory approach, you can efficiently identify the underlying cause of hirsutism and develop an appropriate treatment plan that addresses both the cosmetic concerns and any associated metabolic or reproductive abnormalities.