Recommended Laboratory Evaluation for Suspected Pheochromocytoma
The recommended initial laboratory evaluation for suspected pheochromocytoma should include measurement of plasma free metanephrines or urinary fractionated metanephrines, with plasma free metanephrines being the preferred first-line test due to its superior diagnostic performance (sensitivity 96-100%, specificity 89-98%). 1
Initial Biochemical Testing
- Plasma free metanephrines (normetanephrine and metanephrine) provide the highest diagnostic sensitivity (96-100%) and specificity (89-98%) for pheochromocytoma, making them the preferred initial test 1, 2
- Urinary fractionated metanephrines are an acceptable alternative with high sensitivity (86-97%) and specificity (86-95%) 1, 2
- Plasma free metanephrines should ideally be collected from an indwelling venous catheter, after the patient has been lying supine for 30 minutes to limit false positive results 1
- Plasma methoxytyramine measurement (when available) can help assess the likelihood of malignant disease 3, 1
Interpretation of Results
- Results ≥4 times the upper limit of normal are highly consistent with pheochromocytoma and warrant immediate imaging 1
- Results 2-4 times the upper limit of normal suggest possible pheochromocytoma; repeat testing in 2 months and consider genetic testing 1
- Marginally elevated levels (1-2 times upper limit) may represent false positives; consider repeat testing in 6 months and clonidine suppression test 1
- False positive elevations are usually <4 times the upper limit of normal and may occur with obesity, obstructive sleep apnea, or use of tricyclic antidepressants 1
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, 4
- Clonidine suppression testing is recommended in cases of equivocal results with strong clinical suspicion (100% specificity, 96% sensitivity) 1
- Avoid fine needle biopsy of suspected pheochromocytoma as it is contraindicated due to risk of hypertensive crisis 3, 4
Imaging After Biochemical Confirmation
- MRI is preferred for suspected pheochromocytoma due to risk of hypertensive crisis with IV contrast for CT 3, 4
- For patients with established pheochromocytoma, FDG-PET appears superior to MIBG for detecting malignant tumors, particularly in patients with SDHB mutation 3
- If initial imaging is negative but biochemical evidence is positive, extend imaging to include chest and neck, and consider functional imaging 4
Special Considerations
- For pediatric patients with suspected hereditary syndromes, begin surveillance with plasma metanephrines at age 6-8 years for hereditary paraganglioma/pheochromocytoma syndromes, or age 2 years for von Hippel-Lindau syndrome 1
- Patients with SDHB mutations require more intensive surveillance due to higher risk of malignancy 3, 1
- Plasma free metanephrines can help predict tumor size, location, and presence of metastases 1, 5
Common Pitfalls to Avoid
- Failing to ensure proper patient preparation before testing (medications, posture, fasting status) 1, 6
- Relying solely on imaging without biochemical confirmation 4
- Not considering extra-adrenal locations when adrenal imaging is negative 4
- Overlooking the need for specialized imaging protocols optimized for adrenal evaluation 4
- Performing fine needle biopsy of suspected pheochromocytoma, which is contraindicated 3, 4