What is the recommended diagnostic test for phaeochromocytoma?

Diagnostic Test for Pheochromocytoma

The measurement of plasma free metanephrines is the recommended first-line diagnostic test for pheochromocytoma due to its superior sensitivity (96-100%) and specificity (89-98%). 1

Primary Diagnostic Tests

• Plasma free metanephrines is the most sensitive test (96-100%) for diagnosing pheochromocytoma and should be the first-choice diagnostic test 1, 2
• Urinary fractionated metanephrines is an acceptable alternative with high sensitivity (86-97%) and specificity (86-95%), particularly useful in pediatric patients who are continent of urine 1, 3
• Plasma free metanephrines should ideally be collected from an indwelling venous catheter after the patient has been lying supine for 30 minutes to minimize false positive results 1

Interpretation of Results

• Results >4 times the upper limit of normal are highly consistent with pheochromocytoma and warrant immediate imaging 1
• For moderately elevated levels (1-4 times upper limit of normal), consider:
  • Repeat testing in 2 months 1
  • Clonidine suppression testing, which has 100% specificity and 96% sensitivity for distinguishing true from false positive results 1, 3
• False positive elevations are typically <4 times the upper limit of normal and may occur with:
  • Obesity 1
  • Obstructive sleep apnea 1
  • Use of tricyclic antidepressants 1
  • Certain medications (proper patient preparation is essential) 4

Special Considerations

• For equivocal plasma test results, a 24-hour urine collection for fractionated metanephrines should be performed as a follow-up test 1, 5
• Plasma methoxytyramine measurement can help assess the likelihood of malignant disease 5
• LC-MS/MS analysis is preferred for plasma metanephrine measurement as it minimizes medication interference 1, 4
• Avoid biopsy of suspected pheochromocytoma lesions due to risk of triggering a hypertensive crisis 5

When to Test

Biochemical testing for pheochromocytoma is indicated in patients with:

• Early-onset hypertension (<30 years) 1
• Resistant hypertension 1
• Paroxysmal hypertension with classic symptoms (headache, palpitations, sweating) 1, 5
• Significant blood pressure variability 1
• Family history of pheochromocytoma 1
• Adrenal incidentalomas 6
• Genetic predispositions (MEN2, von Hippel-Lindau syndrome, neurofibromatosis type 1, SDH mutations) 6

Diagnostic Algorithm

1. Measure plasma free metanephrines as first-line test 1, 2
2. If plasma free metanephrines are unavailable, measure urinary fractionated metanephrines 1, 3
3. Interpret results based on degree of elevation:
   • ≥4x upper limit: Proceed to imaging (CT or MRI) 1, 3
   • 1-4x upper limit: Repeat testing and consider clonidine suppression test 1, 3
   • Normal: Pheochromocytoma effectively ruled out (due to high negative predictive value) 2, 7

Common Pitfalls

• Failing to properly prepare patients for testing (medications, posture, fasting status) can lead to false positive results 4, 7
• Using less sensitive tests like plasma/urinary catecholamines or vanillylmandelic acid as initial screening tests may miss cases 2, 8
• Proceeding directly to imaging without biochemical confirmation wastes resources and may lead to unnecessary procedures 7
• Plasma normetanephrine levels show a significant association with age, which should be considered when interpreting results 8