What is the best initial test for diagnosing pheochromocytoma?

Diagnostic Testing for Pheochromocytoma

The best initial test for diagnosing pheochromocytoma is measuring plasma free metanephrines (metanephrine and normetanephrine). 1, 2

Biochemical Testing Algorithm

1. First-line test: Plasma free metanephrines

   • Highest sensitivity (99%) for detecting pheochromocytoma 2
   • Allows reliable exclusion of pheochromocytoma when normal 1
   • Additional measurement of plasma methoxytyramine provides useful information to assess malignancy risk 3

2. Interpretation of plasma metanephrine results:

   • ≥4 times upper limit of normal: Consistent with pheochromocytoma - proceed to imaging 1
   • 2-4 times upper limit of normal: Suspicious - repeat testing in 2 months 1
   • <2 times upper limit of normal: Consider other causes of hypertension

3. Alternative/supplementary tests:

   • 24-hour urine collection for fractionated metanephrines (if plasma testing is equivocal) 1
   • Clonidine suppression test for borderline elevations of plasma normetanephrine 4

Imaging (After Positive Biochemical Testing)

1. First-line imaging:

   • CT scan of abdomen with adrenal protocol 1
   • MRI preferred if pheochromocytoma is strongly suspected due to risk of hypertensive crisis with IV contrast for CT 3

2. Second-line functional imaging (if needed):

   • FDG-PET: Superior for detecting malignant lesions and SDHB-related tumors 3
   • MIBG scintigraphy: If biochemical testing is positive but conventional imaging is negative 1
   • FDOPA-PET: Superior for detection of pheochromocytomas in hereditary syndromes 1

Important Clinical Considerations

• Never perform fine needle biopsy of suspected pheochromocytoma due to risk of hypertensive crisis and tumor seeding 3, 1

• Preoperative preparation is essential:

  • Alpha-adrenergic blockade should be started if normetanephrine levels are ≥2-fold the upper reference limit 1
  • Alpha blockade must be established for 10-14 days before any surgical intervention 1

• High-risk features requiring more extensive evaluation:

  • Tumor size ≥5 cm
  • Extra-adrenal paraganglioma
  • Known SDHB germline mutation
  • Plasma methoxytyramine >3x upper limit of normal 3

Why Plasma Free Metanephrines Are Superior

• Highest diagnostic accuracy with sensitivity of 99% and specificity of 89% 2
• More reliable than urinary tests due to direct measurement of tumor metabolites 2, 5
• Fewer false negatives compared to other biochemical tests 2, 6
• Combining different tests does not improve diagnostic yield beyond plasma free metanephrines alone 2

Post-Diagnostic Follow-up

• Measure plasma/urine metanephrines 8 weeks post-surgery 1
• Imaging 3-6 months post-surgery 1
• Continue surveillance for at least 10 years (lifelong for genetic cases) 1

Plasma free metanephrines provide the most reliable initial test for pheochromocytoma diagnosis, with the highest sensitivity to rule out the condition when negative and sufficient specificity to guide further management when positive.