What is the initial approach for a patient with an ovarian cyst and elevated testosterone levels, possibly indicative of Polycystic Ovary Syndrome (PCOS)?

Initial Approach for Ovarian Cyst with Elevated Testosterone

For patients presenting with ovarian cysts and elevated testosterone levels, the initial diagnostic approach should include comprehensive laboratory testing with total and free testosterone measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS), transvaginal ultrasound for ovarian morphology assessment, and exclusion of other causes of hyperandrogenism to confirm or rule out PCOS. 1

Diagnostic Evaluation Algorithm

Step 1: Laboratory Assessment

• Measure total testosterone and free testosterone using LC-MS/MS (preferred method) 1
  • Free testosterone can be measured by equilibrium dialysis or calculated using free androgen index (FAI)
  • Recent evidence shows cFT, FAI, and TT have the highest sensitivity and specificity for diagnosing biochemical hyperandrogenism in PCOS 2
• Additional hormone tests:
  • Thyroid-stimulating hormone (TSH) to exclude thyroid disease
  • Prolactin to exclude hyperprolactinemia
  • Consider DHEAS and androstenedione (although less accurate than testosterone) 2

Step 2: Imaging

• Transvaginal ultrasound is the gold standard for ovarian morphology assessment 1
  • Look for ≥20 follicles per ovary measuring 2-9mm and/or ovarian volume ≥10ml
  • Use ≥8MHz transducer for optimal visualization
• For patients who cannot tolerate transvaginal ultrasound:
  • MRI of pelvis without contrast is the most reliable alternative, particularly in obese patients 1
  • Transabdominal ultrasound is less reliable but can assess ovarian volume

Step 3: Exclude Other Causes of Hyperandrogenism

• Rule out:
  • Cushing's syndrome (look for buffalo hump, moon facies, abdominal striae)
  • Androgen-secreting tumors (rapid onset of symptoms, very high testosterone)
  • Non-classic congenital adrenal hyperplasia
  • Exogenous androgens
  • Acromegaly
  • Primary ovarian failure 2, 1

Step 4: Metabolic Assessment

• Two-hour oral glucose tolerance test with 75g glucose load 2
• Fasting lipid profile (total cholesterol, LDL, HDL, triglycerides) 2
• Calculate BMI and waist-hip ratio 2

Clinical Pearls and Pitfalls

Important Clinical Features to Assess

• Menstrual history: cycle length >35 days suggests chronic anovulation 1
• Clinical signs of hyperandrogenism: hirsutism, acne, alopecia 1
• Signs of insulin resistance: obesity, acanthosis nigricans 2
• Family history of cardiovascular disease and diabetes 2

Common Pitfalls

• Relying solely on ultrasound for diagnosis is inadequate - PCOS diagnosis requires at least two of three Rotterdam criteria 1
• Using inappropriate testosterone assays or reference ranges can lead to misdiagnosis 1
• Failing to exclude other disorders that can present similarly 1
• Not considering rare presentations - even large ovarian cysts can be associated with PCOS rather than malignancy 3

Special Considerations

• In adolescents with large ovarian cysts, consider PCOS in addition to ruling out malignancy 3
• In patients with insulin resistance, evaluate for metabolic syndrome and diabetes risk 1
• Testosterone-producing solitary ovarian cysts can present with rapid onset of hirsutism and should be distinguished from PCOS 4

By following this structured approach, clinicians can accurately diagnose PCOS or identify other causes of ovarian cysts with hyperandrogenism, leading to appropriate management strategies that address both immediate symptoms and long-term health risks.