What are the next steps for a patient with hyperandrogenism (elevated testosterone level) diagnosed via blood draw?

Next Steps for Hyperandrogenism Diagnosed via Blood Draw

After confirming elevated testosterone via blood draw, immediately repeat the morning testosterone measurement (8-10 AM) using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to verify the finding, then measure LH, FSH, prolactin, and DHEAS to determine the underlying cause. 1

Confirm the Diagnosis

• Repeat morning total testosterone between 8 AM and 10 AM using LC-MS/MS methodology, as a single elevated value requires confirmation before proceeding with extensive workup 1, 2
• Measure free testosterone by equilibrium dialysis or calculate the free androgen index (FAI) if mass spectrometry is unavailable, particularly important in patients with obesity where SHBG alterations affect interpretation 1, 2
• Avoid direct immunoassay methods for free testosterone due to poor accuracy at low serum concentrations 2

Essential Hormone Panel

• Measure LH and FSH to distinguish between ovarian/testicular causes (primary) versus pituitary-hypothalamic causes (secondary) of hyperandrogenism 1
  • An LH/FSH ratio >2 suggests polycystic ovary syndrome (PCOS), which accounts for 95% of hyperandrogenism cases in women 2
• Measure serum prolactin to exclude hyperprolactinemia, especially if LH levels are low or low-normal 1
  • If prolactin is elevated, repeat the measurement to ensure it is not spurious 1
• Measure DHEAS if testosterone is twice the upper limit of normal, as levels >600 mg/dL indicate androgen-secreting adrenal cortical adenoma 3
• Measure 17-hydroxyprogesterone to screen for nonclassic congenital adrenal hyperplasia, a key differential diagnosis 4, 5

Additional Laboratory Testing

• Measure TSH to rule out thyroid disease, which can present with similar symptoms 2
• Check fasting glucose and 2-hour oral glucose tolerance test to screen for diabetes and insulin resistance, commonly associated with PCOS 2
• Obtain fasting lipid panel to assess cardiovascular risk factors 2
• Measure baseline hemoglobin/hematocrit before considering any testosterone-related interventions 6, 1

Imaging Studies When Indicated

• Order pelvic ultrasonography in women to evaluate for polycystic ovaries or ovarian tumors 1, 2
  • Note that isolated polycystic ovaries on ultrasound do not equal PCOS diagnosis, which requires both clinical/biochemical hyperandrogenism and ovulatory dysfunction 2
• Obtain pituitary MRI if prolactin is persistently elevated or if testosterone is <150 ng/dL with low/normal LH, regardless of prolactin levels 1
• Consider adrenal or ovarian imaging if DHEAS is markedly elevated or if virilization is present, suggesting androgen-secreting tumor 3, 5

Clinical Assessment Priorities

• Evaluate for signs of severe hyperandrogenism: virilization (clitoromegaly, voice deepening, breast atrophy) suggests androgen-secreting tumor and requires urgent evaluation 7, 8, 5
• Assess cardiovascular risk factors: dyslipidemia, hypertension, diabetes, smoking status 6, 1
• Document menstrual history: oligomenorrhea or amenorrhea supports PCOS or other ovulatory dysfunction 2, 4
• Evaluate for insulin resistance signs: acanthosis nigricans, central obesity 2
• In men over 40 years: measure PSA and perform digital rectal examination before any testosterone therapy consideration 6, 1

Critical Decision Points

• If testosterone is >200 ng/dL or rapid symptom onset: urgently evaluate for androgen-secreting tumor with imaging 3, 5
• If DHEAS >600 mg/dL: pursue adrenal imaging for adenoma 3
• If 17-hydroxyprogesterone is elevated: confirm nonclassic congenital adrenal hyperplasia with ACTH stimulation test 5
• If signs of Cushing's syndrome present: perform overnight dexamethasone suppression test or 24-hour urinary free cortisol 5

Fertility Considerations

• In men interested in fertility: perform testicular examination and measure FSH before any testosterone therapy, as exogenous testosterone suppresses spermatogenesis 6
• In women with infertility: hyperandrogenism evaluation is essential as it commonly causes anovulation 2, 7

Common Pitfalls to Avoid

• Do not diagnose PCOS in adolescents without longitudinal follow-up, as normal puberty overlaps significantly with PCOS symptoms 4
• SHBG fluctuations from obesity, oral contraceptives, or liver disease can falsely normalize total testosterone while free testosterone remains elevated 2, 3
• Normal testosterone with clear clinical hyperandrogenism (hirsutism, acne) still warrants full evaluation, as SHBG may be reduced in metabolic syndrome 3
• Isolated acne or androgenic alopecia without other features is insufficient for hyperandrogenism diagnosis 7