From the Guidelines
The laboratory workup for pheochromocytoma should start with measuring plasma free metanephrines or 24-hour urinary fractionated metanephrines, as these tests have the highest sensitivity (over 95%) 1.
Key Considerations
- The screening test of choice for pheochromocytoma/paraganglioma is measurement of circulating catecholamine metabolites, specifically plasma free or urinary fractionated metanephrines 1.
- Initial testing should include plasma free metanephrines or 24-hour urinary fractionated metanephrines and catecholamines.
- For plasma testing, blood should be drawn after the patient has been supine and resting for at least 30 minutes, with careful attention to avoid medications that might interfere with results.
- The 24-hour urine collection requires preservatives and specific dietary restrictions (avoiding caffeine, acetaminophen, and certain foods) for 48-72 hours before testing.
Additional Testing
- If initial tests are positive, confirmatory testing may include clonidine suppression test or glucagon stimulation test.
- Additional laboratory tests should include comprehensive metabolic panel, complete blood count, and tests for MEN syndromes if familial disease is suspected (calcitonin, parathyroid hormone, calcium) 1.
- Chromogranin A can serve as a tumor marker.
Imaging Studies
- Once biochemical diagnosis is established, imaging studies like CT, MRI, or functional imaging with MIBG scan or PET should be performed to localize the tumor 1.
- The recent Endocrine Society guideline recommends starting with computed tomography, with magnetic resonance imaging as an alternative and metaiodobenzylguanidine scanning to further evaluate suspected metastatic disease.
Recent Guidelines
- The 2023 guideline from The Journal of Urology suggests screening for pheochromocytoma in patients with adrenal incidentalomas that display >10 HU on non-contrast CT or who have signs/symptoms of catecholamine excess with plasma or 24-hour urinary metanephrines 1.
- However, the most recent and highest quality study 1 prioritizes the measurement of circulating catecholamine metabolites as the initial step in the laboratory workup for pheochromocytoma.
From the Research
Laboratory Workup for Pheochromocytoma
The laboratory workup for pheochromocytoma, a catecholamine-secreting tumor, typically involves biochemical tests to establish the diagnosis. The following are key components of the laboratory workup:
- Measurement of plasma free metanephrines, which has been shown to have high sensitivity and specificity for diagnosing pheochromocytoma 2, 3, 4, 5
- Measurement of urinary fractionated metanephrines, which is also a useful diagnostic test 2, 4, 5
- Measurement of urinary catecholamines, which can be elevated in patients with pheochromocytoma, but has lower sensitivity and specificity compared to plasma free metanephrines and urinary fractionated metanephrines 3, 5
- Measurement of plasma catecholamines, which can be elevated in patients with pheochromocytoma, but has lower sensitivity and specificity compared to plasma free metanephrines and urinary fractionated metanephrines 5
Diagnostic Criteria
The diagnostic criteria for pheochromocytoma typically involve a combination of clinical presentation, biochemical tests, and imaging studies. The following are key diagnostic criteria:
- Elevated plasma free metanephrines or urinary fractionated metanephrines 2, 4, 5
- Clinical presentation of hypertension, unexplained spells, incidental adrenal masses, or a family history of pheochromocytoma 2, 3
- Imaging studies, such as computed tomography (CT) or magnetic resonance imaging (MRI), to confirm the presence of a tumor 2
Special Considerations
In some cases, pheochromocytoma may be extra-adrenal in origin, and special consideration should be given to these cases. For example:
- Extra-adrenal pheochromocytoma of the urinary bladder has been reported in rare cases, and diagnosis may require a combination of biochemical tests and imaging studies 6
- Measurement of methoxytyramine, the O-methylated metabolite of dopamine, may be useful in diagnosing extra-adrenal pheochromocytoma 4