What is the initial evaluation for a suspected Leydig cell tumor with elevated testosterone levels?

Initial Evaluation for Leydig Cell Tumor with Elevated Testosterone

The initial evaluation for a suspected Leydig cell tumor with elevated testosterone should include high-frequency testicular ultrasound, comprehensive hormonal panel (including testosterone, LH, FSH, hCG, AFP, and LDH), and CT scan of the abdomen and pelvis. 1

Clinical Presentation and Initial Assessment

Leydig cell tumors are rare, accounting for approximately 1-3% of all testicular neoplasms. These tumors can produce steroid hormones, particularly testosterone, which may lead to their clinical presentation.

Key clinical features to assess:

• Testicular mass (may be palpable or non-palpable)
• Signs of hyperandrogenism (in males, this may be subtle)
• Gynaecomastia (present in approximately 1% of patients with testicular tumors) 1

Diagnostic Algorithm

Step 1: Laboratory Evaluation

• Serum testosterone levels: Significantly elevated in Leydig cell tumors
• Luteinizing hormone (LH) and follicle-stimulating hormone (FSH): Often suppressed due to negative feedback from elevated testosterone
• Tumor markers:
  • Alpha-fetoprotein (AFP): Should be normal in pure Leydig cell tumors
  • Beta-human chorionic gonadotropin (β-hCG): Should be normal in pure Leydig cell tumors
  • Lactate dehydrogenase (LDH): May be elevated but has low specificity 1

Step 2: Imaging Studies

• High-frequency testicular ultrasound (>10 MHz): First-line imaging modality to:

  • Confirm presence of testicular mass
  • Determine if the mass is intratesticular or extratesticular
  • Assess size and characteristics of the lesion
  • Evaluate the contralateral testicle 1

• CT scan with contrast of abdomen and pelvis: To evaluate for:

  • Metastatic disease
  • Lymphadenopathy
  • Other potential sources of androgen excess 1

Step 3: Additional Testing (if diagnosis remains unclear)

• Selective venous sampling: If imaging is negative despite strong clinical suspicion and elevated testosterone, consider selective gonadal vein sampling to lateralize the source of testosterone production 2, 3

Differential Diagnosis

When evaluating a patient with elevated testosterone and suspected Leydig cell tumor, consider:

• Other testicular tumors (seminoma, non-seminoma)
• Adrenal tumors or hyperplasia
• Exogenous testosterone use
• Congenital adrenal hyperplasia (in younger patients)

Management Considerations

The definitive diagnosis of a Leydig cell tumor requires histopathological examination. For suspected testicular Leydig cell tumors:

• Radical inguinal orchiectomy is the standard approach for most testicular tumors
• Testis-sparing surgery may be considered for small tumors (<2 cm) in select cases 1

Important Caveats

1. Negative imaging doesn't rule out tumor: Some Leydig cell tumors may be occult and not visualized on conventional imaging despite causing significant hormonal abnormalities 2, 3

2. Tumor marker limitations: Normal tumor markers (AFP, β-hCG) don't exclude testicular neoplasms. Approximately 40-60% of patients with testicular tumors may have elevated LDH, but this has low specificity 1

3. Post-surgical monitoring: Following tumor removal, testosterone levels should be monitored to confirm adequate resection and detect recurrence 3

4. Fertility considerations: Patients should be offered semen preservation before orchiectomy when feasible, as both the tumor and its treatment may impact fertility 1

By following this systematic approach, clinicians can effectively evaluate patients with suspected Leydig cell tumors and elevated testosterone levels, ensuring appropriate diagnosis and management.