24-Hour Urinary Metanephrines Is the Best Single Screening Test for Pheochromocytoma
The 24-hour urinary metanephrines (fractionated metanephrines) is the best single screening test using 24-hour urine for pheochromocytoma. This test has superior diagnostic performance compared to other urinary assays including VMA, 5-hydroxyindole acetic acid, catecholamines, and homovanillic acid (HVA).
Evidence Supporting Urinary Metanephrines
Diagnostic Performance
- 24-hour urinary fractionated metanephrines demonstrate excellent sensitivity (97%) for detecting pheochromocytoma 1
- Urinary metanephrines have been shown to have superior diagnostic performance compared to:
Clinical Guidelines Support
- The American College of Medical Genetics recommends 24-hour urinary fractionated metanephrines as an alternative first-line test with sensitivity of 86-97% and specificity of 86-95% 3
- When plasma testing is equivocal, guidelines specifically recommend "a follow-up 24-hour urine collection for catecholamines and metanephrines" 4
Comparison of Testing Options
| Test | Sensitivity | Specificity | Comments |
|---|---|---|---|
| Urinary Fractionated Metanephrines | 97% | 69-94% | Best urinary test; highest sensitivity [1,2] |
| Urinary Catecholamines | 84-86% | 88-99% | Good but less sensitive than metanephrines [1,2] |
| Urinary VMA | 64-72% | 95-96% | Poorest sensitivity of all tests [1,2] |
| 5-HIAA | N/A | N/A | Not indicated for pheochromocytoma (used for carcinoid) |
| Urinary HVA | N/A | N/A | Not indicated for pheochromocytoma (used for neuroblastoma) |
Important Clinical Considerations
When to Use 24-Hour Urine Testing
- When plasma testing is equivocal (less than fourfold elevation) 4
- In centers where plasma free metanephrine testing is not available
- For confirmation of positive plasma results
Interpretation
- Results >4 times upper limit of normal are consistent with pheochromocytoma 3
- When using a cutoff value for metanephrine + normetanephrine of 1000 ng/mg creatinine, sensitivity is 97.6% and specificity is 100% 5
- When using a standard of >500 ng/mg creatinine for either metanephrine or normetanephrine, both sensitivity and specificity reach 100% 5
Potential Pitfalls
- Certain medications can interfere with test results (tricyclic antidepressants, levodopa, sympathomimetics)
- Food interactions (caffeine, vanilla) may affect results
- Proper collection technique is essential for accurate results
- Incomplete 24-hour collections can lead to false negatives
Conclusion
While plasma free metanephrines have emerged as the preferred initial test for pheochromocytoma with the highest sensitivity (96-100%) 3, 2, when specifically considering 24-hour urine tests, fractionated metanephrines clearly outperform VMA, catecholamines, 5-HIAA, and HVA for pheochromocytoma screening.