What are the initial diagnostic tests for suspected pheochromocytoma?

Initial Diagnostic Tests for Suspected Pheochromocytoma

The measurement of plasma free metanephrines is the initial diagnostic test of choice for suspected pheochromocytoma, with the highest sensitivity (96-100%) and specificity (89-98%) as a single test. 1, 2

Biochemical Testing Algorithm

First-Line Tests

1. Plasma free metanephrines

   • Highest sensitivity (96-100%) and specificity (89-98%) 2
   • Should be collected after patient has been lying supine for 30 minutes 1
   • Results >4 times upper limit of normal are highly consistent with pheochromocytoma 1

2. Alternative first-line test: 24-hour urinary fractionated metanephrines

   • Sensitivity: 86-97% and specificity: 86-95% 1, 2
   • Recommended when plasma testing is unavailable 3
   • Remains the diagnostic test of choice in many centers due to wider availability 3

Interpretation of Results

• Strongly positive results (>4× upper limit of normal): Proceed directly to imaging 1
• Borderline elevations: Consider clonidine suppression test (100% specificity, 96% sensitivity) 1
• Negative results: Effectively rule out pheochromocytoma (high negative predictive value) 4

Important Considerations for Testing

Preanalytical Factors

• Ensure proper patient preparation:
  • Avoid medications that can interfere with test results (e.g., sulfasalazine) 5
  • Patient should be supine for 30 minutes before plasma sampling 1
  • Avoid stress and exercise before testing

Clinical Pearls

• Combining different biochemical tests does not improve diagnostic yield beyond plasma free metanephrines alone 2
• Plasma free metanephrines have the highest sensitivity, making them ideal for ruling out disease 2, 4
• A positive test result only moderately increases suspicion of disease when screening for sporadic pheochromocytoma 4
• In rare cases, pheochromocytoma may present with elevated metanephrines as the only biochemical finding 6

Next Steps After Positive Biochemical Testing

Imaging Studies

• CT scan of abdomen: First-line imaging modality 1
• MRI: Alternative imaging option, preferred in patients with suspected pheochromocytoma to avoid contrast-induced hypertensive crisis 3, 1
• Functional imaging: For suspected metastatic disease or to confirm diagnosis 1
  • 123I-MIBG scintigraphy for non-metastatic adrenal pheochromocytoma
  • 18F-FDG PET for SDHB-related metastatic pheochromocytomas
  • 18F-FDOPA PET for head and neck paragangliomas

Genetic Testing Considerations

• Approximately 25% of pheochromocytomas are hereditary 1
• Consider genetic testing in all patients, especially those with:
  • Young age at diagnosis
  • Bilateral or multifocal disease
  • Extra-adrenal location
  • Family history of pheochromocytoma or related syndromes

Common Pitfalls to Avoid

1. Proceeding to imaging before biochemical confirmation

   • Imaging should only be pursued after biochemical evidence of pheochromocytoma 1

2. Ignoring medication interference

   • Many medications can cause false positive results 5
   • Review all medications before testing

3. Inadequate patient preparation

   • Failure to have patient supine before plasma sampling
   • Not controlling for stress, exercise, or diet

4. Relying solely on non-specific symptoms

   • While the classic triad of headache, sweating, and palpitations is suggestive, biochemical confirmation is essential

5. Overlooking the possibility of genetic syndromes

   • Failure to consider hereditary causes may miss important diagnostic and prognostic information

By following this diagnostic algorithm, clinicians can effectively rule out or confirm pheochromocytoma, leading to appropriate management and improved patient outcomes.