What is the appropriate workup for suspected pheochromocytoma?

Diagnostic Workup for Pheochromocytoma

The appropriate workup for suspected pheochromocytoma should begin with plasma free metanephrines as the initial biochemical test, followed by anatomical imaging with CT or MRI after positive biochemical confirmation, and functional imaging in select cases to detect multifocal or metastatic disease. 1, 2

Initial Biochemical Testing

• Plasma free metanephrines (normetanephrine and metanephrine) is the most sensitive (99%) and specific (89%) single test for diagnosing pheochromocytoma and should be the first-line diagnostic test 1, 3
• If plasma testing is equivocal (less than fourfold elevation), perform a follow-up 24-hour urine collection for catecholamines and metanephrines 4, 2
• Consider measuring plasma methoxytyramine (when available) as it provides useful information to assess the likelihood of malignancy 1, 2
• Be aware of potential false positives from medications (such as sulfasalazine, amphetamines) that can interfere with metanephrine measurements 5, 6
• Rare cases of symptomatic pheochromocytoma with normal urinary catecholamines have been reported, highlighting the superiority of plasma free metanephrines 7, 8

Imaging Studies (After Positive Biochemical Testing)

• Localization of the pheochromocytoma is generally done by CT or MRI of the abdomen 4, 1
• CT imaging provides excellent spatial resolution for tumor localization and should include the chest to evaluate for potential metastatic disease 1
• MRI is particularly useful for pregnant patients and those with contrast allergies 1

Functional Imaging (For Specific Scenarios)

• Functional imaging is indicated in the following scenarios:

  • Suspected multifocal disease
  • Extra-adrenal paragangliomas
  • Suspected metastatic disease
  • Genetic syndromes associated with pheochromocytoma
  • Biochemically positive cases with negative conventional imaging 4

• Options for functional imaging include:

  • Meta-iodobenzylguanidine (MIBG) scintigraphy - helpful for detecting multifocal disease 4, 1
  • 3,4-dihydroxy-6-18F-fluoro-L-phenylalanine positron emission tomography (FDOPA-PET) - superior for detection of pheochromocytomas in hereditary syndromes 4
  • FDG-PET - particularly useful for SDHB-related tumors 2

Special Considerations

• Avoid biopsy of suspected pheochromocytoma due to risk of hypertensive crisis and tachyarrhythmia 4, 2
• Biochemical screening in asymptomatic patients is not recommended unless they have specific risk factors 4, 2
• Consider genetic testing, particularly in patients with:
  • Family history of pheochromocytoma/paraganglioma
  • Young age at diagnosis (<40 years)
  • Bilateral or multifocal disease
  • Extra-adrenal location 1

Risk Factors for Malignancy

• Tumor size ≥5 cm
• Extra-adrenal paraganglioma
• SDHB germline mutation
• Elevated plasma methoxytyramine (>3x upper limit) 1

Follow-up Protocol

• After successful treatment, perform biochemical testing approximately 14 days following surgery to check for remaining disease 1
• Long-term follow-up should include annual surveillance with plasma metanephrines 4, 1
• For patients with high-risk features (PASS score ≥4, large primary tumor, SDHB mutation), consider extended and life-long monitoring 4