Diagnostic Testing for Pheochromocytoma
The measurement of plasma free metanephrines is the recommended first-line diagnostic test for pheochromocytoma, with the highest sensitivity (96-100%) and specificity (89-98%) among all biochemical tests. 1, 2
Primary Diagnostic Tests
- Plasma free metanephrines is the preferred initial test due to its superior diagnostic performance, with nearly 100% sensitivity for detecting pheochromocytoma 1, 3
- Urinary fractionated metanephrines is an acceptable alternative with high sensitivity (86-97%) and specificity (86-95%) 1, 2
- For optimal results, plasma free metanephrines should be collected from an indwelling venous catheter after the patient has been lying supine for 30 minutes to limit false positive results 2
Interpretation of Results
- Results ≥4 times the upper limit of normal are highly consistent with pheochromocytoma and warrant immediate imaging 1, 2
- Results 2-4 times the upper limit of normal suggest possible pheochromocytoma; repeat testing in 2 months and consider genetic testing 1, 2
- Marginally elevated levels (1-2 times upper limit) may represent false positives; consider repeat testing in 6 months and clonidine suppression test 1, 2
Follow-up Testing for Equivocal Results
- If plasma testing is equivocal (less than fourfold elevation), perform a 24-hour urine collection for catecholamines and metanephrines 1, 2
- Clonidine suppression testing is recommended in cases of equivocal results with strong clinical suspicion, with 100% specificity and 96% sensitivity 4, 1
- The clonidine suppression test is regarded as negative when there is a marked reduction of plasma catecholamines 4
Imaging After Biochemical Confirmation
- MRI is preferred for suspected pheochromocytoma due to risk of hypertensive crisis with IV contrast for CT 1, 2
- For patients with established pheochromocytoma, FDG-PET appears superior to MIBG for detecting malignant tumors, particularly in patients with SDHB mutation 2
- If initial imaging is negative but biochemical evidence is positive, extend imaging to include chest and neck, and consider functional imaging 4
Special Considerations
- Avoid fine needle biopsy of suspected pheochromocytoma as it is contraindicated due to risk of hypertensive crisis 4, 2
- Approximately 35% of pheochromocytomas/paragangliomas are hereditary, so genetic testing should be considered, especially in younger patients 1, 5
- Patients with SDHB mutations require more intensive surveillance due to higher risk of malignancy 1, 2
- For pediatric patients with suspected hereditary syndromes, begin surveillance at age 6-8 years for hereditary paraganglioma/pheochromocytoma syndromes, or age 2 years for von Hippel-Lindau syndrome 1, 2
Common Pitfalls to Avoid
- False positive elevations are usually <4 times the upper limit of normal and can occur with obesity, obstructive sleep apnea, or use of tricyclic antidepressants 1
- Failing to ensure proper patient preparation before testing (medications, posture, fasting status) can lead to false results 2
- Relying solely on imaging without biochemical confirmation is not recommended 2
- Not considering extra-adrenal locations when adrenal imaging is negative can lead to missed diagnoses 2