What is the initial step in testing for pheochromocytoma?

Testing for Pheochromocytoma

The initial step in testing for pheochromocytoma is measurement of plasma free metanephrines, which has the highest sensitivity (96-100%) and specificity (89-98%) as a single test. 1, 2

Biochemical Testing Algorithm

First-Line Testing

• Plasma free metanephrines is the preferred initial test 3, 2

  • Highest sensitivity (99%) for detecting pheochromocytoma
  • Reasonable specificity (89%)
  • Ideally collected after patient has been lying supine for 30 minutes 2

• Alternative first-line test: 24-hour urinary fractionated metanephrines 2

  • Sensitivity: 86-97%
  • Specificity: 86-95%
  • Appropriate once patients are continent of urine 2

Interpreting Results

• >4 times upper limit of normal: Consistent with pheochromocytoma; proceed to imaging 2, 1
• 2-4 times upper limit of normal: Repeat testing in 2 months 2
• Marginally elevated: Repeat testing in 6 months or consider clonidine suppression test 2

Confirmatory Testing

• Clonidine suppression test for borderline elevations 2, 1
  • 100% specificity and 96% sensitivity
  • Test is negative (rules out pheochromocytoma) if there is marked reduction of plasma metanephrines 2

Important Considerations

Factors Affecting Test Accuracy

• Several medications and foods can interfere with metanephrine analysis 2
• Common false positives occur with:
  • Tricyclic antidepressants 2
  • Obesity 2
  • Obstructive sleep apnea 2

Clinical Context

• Testing should be prioritized in patients with:
  • Hypertension that is resistant to treatment 2
  • Paroxysmal hypertension 2
  • Hypertension with headache, palpitations, or sweating 2
  • Age >30 years with hypertension (in NF1 patients) 2
  • Pregnancy with hypertension 2
  • Family history of pheochromocytoma 1

Next Steps After Biochemical Confirmation

• Imaging should only be pursued after biochemical evidence of pheochromocytoma 2, 1
• CT scan of the abdomen is the first-line imaging modality 2, 1
• MRI is an alternative imaging option 2, 1
• Functional imaging (meta-iodobenzylguanidine scanning or FDOPA-PET) for suspected metastatic disease 2, 1

Common Pitfalls to Avoid

1. Don't start with imaging - biochemical testing must precede imaging 2, 1
2. Don't perform biopsy of suspected pheochromocytoma - potentially dangerous and should be avoided 2, 1
3. Don't ignore borderline elevations - they require follow-up or confirmatory testing 2
4. Don't forget to screen for genetic syndromes - approximately 25% of pheochromocytomas are hereditary 4, 5
5. Don't delay diagnosis - average delay in diagnosis is 3 years, which increases morbidity and mortality 2

By following this systematic approach to testing for pheochromocytoma, early diagnosis can be achieved, allowing for appropriate preoperative management and ultimately surgical cure in most cases.