Should I get plasma free metanephrines or a 24-hour urine collection for fractionated metanephrines to measure metanephrine levels?

Plasma Free Metanephrines vs. 24-Hour Urine Collection for Measuring Metanephrine Levels

Plasma free metanephrines is the preferred first-line test for measuring metanephrine levels due to its superior sensitivity (96-100%) compared to 24-hour urine collection (86-97%). 1

Diagnostic Performance Comparison

Plasma Free Metanephrines

• Sensitivity: 96-100% 1
• Specificity: 89-98% 1
• Advantages:
  • Higher sensitivity for detecting pheochromocytoma 2
  • No false-negative results in most studies 2
  • More convenient for patients (single blood draw vs. 24-hour collection)
  • Particularly valuable in high-risk patients with familial endocrine syndromes 3
  • Preferred for patients who cannot reliably collect 24-hour urine 1

24-Hour Urine Fractionated Metanephrines

• Sensitivity: 86-97% 1
• Specificity: 86-95% 1
• Advantages:
  • Fewer false-positive results (higher specificity) 3
  • Better for low-risk patients where false positives are more concerning 3
  • Acceptable alternative once patients are continent of urine 4

Clinical Decision Algorithm

1. For most patients: Use plasma free metanephrines as the first-line test 4, 1

   • Requires proper collection technique: patient should be lying supine for 30 minutes before collection 1
   • Avoid interfering foods and medications prior to testing 1

2. For specific patient populations:

   • High-risk patients (familial syndromes, known genetic mutations): Plasma free metanephrines 3
   • Low-risk patients (where false positives are more concerning): 24-hour urine collection may be preferred 3
   • Children or incontinent patients: Plasma free metanephrines 4

3. Interpretation of results:

   • Plasma metanephrines ≥4 times upper limit of normal: Consistent with disease, proceed with imaging 4, 1
   • Plasma metanephrines 2-4 times upper limit of normal: Repeat testing in 2 months 4
   • Marginally elevated levels: Repeat testing in 6 months or consider clonidine suppression test 4, 1

Important Considerations

• Normal plasma metanephrine levels effectively exclude pheochromocytoma, whereas normal urine levels may still miss some cases 2
• Adrenal pheochromocytomas can sometimes be missed by urinary testing, particularly in patients with familial syndromes 3
• For screening patients with adrenal incidentalomas that display ≥10 HU on non-contrast CT or who have signs/symptoms of catecholamine excess, either plasma or 24-hour urinary metanephrines are acceptable 4

Potential Pitfalls

• False positives with plasma testing can occur due to:

  • Medications (tricyclic antidepressants, MAO inhibitors, sympathomimetics)
  • Stress or acute illness
  • Improper collection technique (not resting supine before collection)
  • Failure to fast

• False negatives with urine testing can occur due to:

  • Incomplete 24-hour collection
  • Small tumors, especially in familial syndromes
  • Intermittent catecholamine secretion

For optimal results, ensure proper collection techniques and patient preparation regardless of which test is chosen.