How do you diagnose androgen secreting ovarian tumors?

Diagnostic Approach to Androgen-Secreting Ovarian Tumors

The diagnosis of androgen-secreting ovarian tumors requires measurement of serum testosterone as the first-line laboratory test, along with imaging studies including pelvic ultrasound and CT/MRI to localize the tumor. 1

Clinical Presentation

Androgen-secreting ovarian tumors typically present with:

• Rapidly progressive hirsutism and virilization
• Menstrual irregularities
• Male-pattern baldness
• Deepening of voice
• Clitoromegaly
• Increased muscle mass
• Acne

The key clinical feature that distinguishes these tumors from other causes of hyperandrogenism is the rapid onset and progression of symptoms, particularly in postmenopausal women or prepubertal girls.

Diagnostic Algorithm

Step 1: Laboratory Testing

• First-line tests:

  • Serum total testosterone (TT) - levels >200 ng/dL (>7 nmol/L) strongly suggest an androgen-secreting tumor 2
  • Free testosterone (FT) or calculated free testosterone (cFT) using equilibrium dialysis or calculated using free androgen index (FAI) 1

• Second-line tests:

  • Androstenedione
  • Dehydroepiandrosterone sulfate (DHEAS)
  • 17-hydroxyprogesterone
  • Complete blood count
  • Liver and renal function tests 1

Step 2: Imaging Studies

• Pelvic ultrasound - first imaging modality of choice
• Abdomino-pelvic CT scan - for better characterization of the mass
• MRI - particularly useful for small tumors
• Chest X-ray - to rule out metastasis in suspicious cases
• PET scan - for selected cases 1

Step 3: Differential Diagnosis Testing

• Low-dose dexamethasone suppression test - to differentiate ovarian from adrenal sources of androgens
• GnRH agonist test - to assess ovarian response
• Selective venous sampling - when imaging is negative but clinical suspicion is high 2

Tumor Types and Specific Markers

1. Sertoli-Leydig cell tumors:

   • Most common androgen-secreting ovarian tumors (0.5% of all ovarian neoplasms)
   • Typically affect women under 30 years
   • Usually unilateral and benign 3
   • Testosterone is the primary elevated hormone

2. Steroid cell tumors:

   • Can produce extremely high levels of testosterone, androstenedione, DHEAS, and 17-hydroxyprogesterone 4
   • Often present with severe virilization

3. Leydig cell tumors:

   • Common in postmenopausal women
   • Typically small and may be missed on conventional imaging 5
   • Characterized by elevated testosterone with normal DHEAS

4. Granulosa cell tumors:

   • Primarily secrete estrogen but can occasionally produce androgens
   • Inhibin is a useful tumor marker 1

Common Pitfalls and Caveats

1. Misdiagnosis as PCOS - Androgen-secreting tumors can be misdiagnosed as polycystic ovary syndrome, delaying proper treatment. Testosterone levels >200 ng/dL should prompt evaluation for an androgen-producing tumor 6.

2. Negative imaging - Some androgen-secreting tumors, particularly Leydig cell tumors, can be very small (<1 cm) and may not be detected on conventional imaging. Selective venous sampling may be necessary when clinical suspicion is high despite negative imaging 5.

3. Adrenal vs. ovarian source - Distinguishing between ovarian and adrenal sources of androgens can be challenging. The pattern of androgen elevation can help: predominant testosterone elevation suggests ovarian source, while predominant DHEAS elevation suggests adrenal source 1.

4. Laboratory method considerations - Liquid chromatography with tandem mass spectrometry (LC-MS/MS) has superior sensitivity and specificity for measuring androgens compared to direct immunoassay methods 1.

By following this systematic approach, clinicians can effectively diagnose androgen-secreting ovarian tumors, leading to appropriate surgical intervention and improved outcomes for affected patients.