From the Guidelines
The laboratory workup for pheochromocytoma should begin with biochemical testing for catecholamines and their metabolites, specifically measurement of circulating catecholamine metabolites such as plasma free or urinary fractionated metanephrines, as recommended by the most recent guidelines 1.
Key Considerations
- The screening test of choice for pheochromocytoma is measurement of circulating catecholamine metabolites, with plasma free metanephrines having a sensitivity of 96%−100% and specificity of 89%−98%, and urinary fractionated metanephrines having a sensitivity of 86%−97% and specificity of 86%−95% 1.
- Initial screening tests include 24-hour urinary fractionated metanephrines and catecholamines, or plasma free metanephrines, which have higher sensitivity.
- Patients should avoid certain medications, such as tricyclic antidepressants, MAO inhibitors, and sympathomimetics, and substances like caffeine, alcohol, and strenuous exercise for 24 hours before testing.
- If initial biochemical tests are positive, imaging studies like CT or MRI of the abdomen and pelvis should follow to localize the tumor, as recommended by the recent Endocrine Society guideline 1.
Biochemical Testing
- Plasma free metanephrines require blood collection after the patient has been supine and resting for at least 30 minutes, with the patient fasting and avoiding medications that might interfere with results.
- 24-hour urinary fractionated metanephrines and catecholamines require patients to collect all urine over a 24-hour period in a container with acid preservative.
- Clonidine-suppression testing can be used to further evaluate suspected false positives, with 100% specificity and 96% sensitivity of failure to reduce plasma metanephrines by 40% 1.
Imaging Studies
- Imaging should be pursued only after biochemical evidence for a pheochromocytoma has been obtained.
- Computed tomography is recommended as the initial imaging modality, with magnetic resonance imaging as an alternative, and metaiodobenzylguanidine scanning to further evaluate suspected metastatic disease 1.
From the Research
Laboratory Workup for Pheochromocytoma
The laboratory workup for pheochromocytoma typically involves measurements of plasma free metanephrines or urinary fractionated metanephrines.
- Plasma free metanephrines have a high diagnostic sensitivity of 98% and specificity of 92% 2
- Urinary fractionated metanephrines also have high sensitivity and specificity, with values of 97% and 69%, respectively 3
- Measurements of plasma catecholamines, urinary catecholamines, and urinary vanillylmandelic acid can also be used, but have lower sensitivity and specificity compared to plasma free metanephrines and urinary fractionated metanephrines 3
- A new radioimmunoassay (RIA) for the measurement of free metanephrines in plasma has been developed and shows good agreement with tandem mass spectrometry (LC-MS/MS) method 4
Diagnostic Tests
The following diagnostic tests can be used to diagnose pheochromocytoma:
- Plasma free metanephrines
- Urinary fractionated metanephrines
- Plasma catecholamines
- Urinary catecholamines
- Urinary vanillylmandelic acid
- Radioimmunoassay (RIA) for free metanephrines in plasma
Test Interpretation
- A positive test result indicates the presence of pheochromocytoma, but a negative result does not completely rule out the diagnosis 2, 5
- Borderline increased results should be followed up with repeat testing to either exclude or confirm diagnosis 6
- The choice of test and interpretation of results should be individualized based on patient characteristics and clinical presentation 3