What lab work is used to diagnose pheochromocytoma?

Laboratory Workup for Pheochromocytoma Diagnosis

The most sensitive and specific initial laboratory test for diagnosing pheochromocytoma is measurement of plasma free metanephrines as a single test. 1

Primary Biochemical Testing

First-Line Testing

• Plasma free metanephrines (normetanephrine and metanephrine)
  • Highest sensitivity (99%) for detecting pheochromocytoma 2
  • Should be collected after 30 minutes of rest in the supine position 1
  • Most sensitive single test for clinically suspected pheochromocytoma 1

Follow-up Testing (if plasma results are equivocal)

• 24-hour urine collection for:
  • Catecholamines and metanephrines (recommended if plasma testing shows less than fourfold elevation) 1
  • Urinary free metanephrines have shown 100% sensitivity in some studies 3

Special Considerations for Sample Collection

• Plasma sampling requirements:

  • Patient should rest 30 minutes in supine position before collection
  • Normal reference range should be based on samples collected in the same manner 1
  • 3-methoxytyramine should be sampled after overnight fast 1
  • If sampling is done sitting, 25% of results will be falsely elevated compared to supine reference 1

• Laboratory technique:

  • Analysis should be performed using liquid chromatography with detection by mass spectrometry 1

Interpretation of Results

• High levels of metanephrine suggest adrenal pheochromocytoma
• Isolated elevation of 3-methoxytyramine suggests paraganglioma (can also occur in rare dopamine-producing pheochromocytomas) 1
• Levels of 3-methoxytyramine correlate with tumor size and presence of metastasis 1

Confirmatory Testing for Borderline Results

• Clonidine suppression test can be used for patients with borderline elevations 4
  • Blood samples before and 3 hours after clonidine administration
  • Negative test: clonidine-induced fall in normetanephrine >40% or to below upper reference limit
  • 100% specificity for excluding pheochromocytoma when using normetanephrine as the marker 4

Common Pitfalls and Caveats

• Medications that can interfere with test results:

  • Tricyclic antidepressants and monoamine oxidase inhibitors increase levels of metanephrine and normetanephrine
  • Levodopa raises levels of 3-methoxytyramine 1

• False positives can occur due to:

  • Improper patient positioning during collection (sitting vs. supine)
  • Stress or anxiety during blood draw
  • Failure to follow fasting requirements for 3-methoxytyramine

• Avoid biopsy of suspected pheochromocytoma/paraganglioma before biochemical testing as it can trigger hypertensive crisis and tachyarrhythmia 1

Testing Algorithm

1. Initial test: Plasma free metanephrines (most sensitive and specific single test)
2. If equivocal results (less than fourfold elevation): Proceed to 24-hour urine collection for catecholamines and metanephrines
3. If still uncertain: Consider clonidine suppression test for borderline elevations
4. After biochemical confirmation: Proceed to anatomical imaging (CT/MRI) for tumor localization

Remember that while biochemical testing is the cornerstone of diagnosis, imaging studies are subsequently required for tumor localization once biochemical evidence confirms the presence of a pheochromocytoma.