What tests are used to diagnose pheochromocytoma (pheo) with hypertension?

Diagnosis of Pheochromocytoma with Hypertension

Plasma free metanephrines is the most sensitive and specific single test for diagnosing pheochromocytoma in patients with hypertension, with sensitivity of 96-100% and specificity of 89-98%. 1

Primary Diagnostic Tests

Biochemical Testing

1. First-line test: Plasma free metanephrines

   • Highest sensitivity (96-100%) and specificity (89-98%) 1
   • Elevation >4 times the upper limit of normal is highly specific for pheochromocytoma 1
   • Superior to other tests for excluding or confirming pheochromocytoma 2

2. Alternative or confirmatory tests:

   • 24-hour urine collection for fractionated metanephrines (sensitivity 97%, specificity 69%) 2
   • Should be performed if plasma testing is equivocal (less than fourfold elevation) 3

Imaging Studies (after biochemical confirmation)

1. CT or MRI of abdomen and pelvis

   • First-line imaging to localize the tumor 3, 1
   • MRI preferred over CT for suspected pheochromocytoma due to risk of hypertensive crisis with IV contrast during CT 3

2. Functional imaging (for confirming diagnosis or detecting multifocal disease):

   • MIBG scintigraphy 3
   • FDOPA-PET (superior for hereditary pheochromocytoma syndromes) 3
   • FDG-PET (particularly useful in SDHB mutation and malignant tumors) 3
   • DOTA-TATE-PET 3

Diagnostic Algorithm

1. Suspect pheochromocytoma in patients with:

   • Paroxysmal or sustained hypertension
   • Hypertension with headache, palpitations, or sweating
   • Hypertension in patients >30 years with NF1
   • Hypertension during pregnancy
   • Orthostatic hypotension (in epinephrine-predominant tumors) 1

2. Biochemical confirmation:

   • Measure plasma free metanephrines
   • If elevated >4x normal: diagnosis highly likely
   • If equivocal (<4x elevation): perform 24-hour urine collection for metanephrines and catecholamines 3, 1

3. Tumor localization:

   • Perform MRI of abdomen and pelvis (preferred) or CT
   • If negative but biochemical testing positive: proceed to functional imaging
   • If multiple tumors suspected: use functional imaging 3

Important Clinical Considerations

• Fine needle biopsy of suspected pheochromocytoma is contraindicated due to risk of hypertensive crisis 3
• Biochemical testing should be performed before imaging studies 4
• In patients with known pheochromocytoma, long-term follow-up includes annual surveillance with plasma metanephrines 3
• False negatives can occur with plasma catecholamine measurements but are rare with urinary metanephrines 5
• Genetic testing should be considered in all patients with confirmed pheochromocytoma, especially those under 50 years 6

Pitfalls to Avoid

• Relying solely on plasma catecholamines, which can give falsely negative results 5
• Performing imaging before biochemical confirmation 4
• Using urinary vanillylmandelic acid (VMA) as the only test (lowest sensitivity at 64%) 2
• Performing fine needle biopsy on suspected adrenal pheochromocytoma 3
• Administering IV contrast for CT without proper alpha-blockade preparation 3

The diagnostic approach should follow this sequence: clinical suspicion → biochemical confirmation with plasma free metanephrines → anatomical and functional imaging for localization → genetic testing consideration. This approach ensures the highest diagnostic accuracy and patient safety.