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 evidence 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% 1.
- Initial screening tests include 24-hour urinary fractionated metanephrines and catecholamines, or plasma free metanephrines, which have higher sensitivity.
- Patients should avoid medications that can interfere with results, such as tricyclic antidepressants, levodopa, and sympathomimetics, for at least 2 weeks prior to testing.
- If initial tests are positive, confirmatory testing may include clonidine suppression testing, which has 100% specificity and 96% sensitivity of failure to reduce plasma metanephrines by 40% 1.
Imaging and Further Evaluation
- Imaging studies such as CT or MRI of the abdomen and pelvis should be performed to localize the tumor only after biochemical evidence for a pheochromocytoma has been obtained.
- For patients with familial syndromes or extra-adrenal disease, additional testing may include MIBG scintigraphy or PET scanning.
- Genetic testing should be considered, particularly in patients with bilateral tumors, young age of onset, or family history, to evaluate for hereditary syndromes like MEN2, von Hippel-Lindau disease, or neurofibromatosis type 1.
Recent Recommendations
- The 2023 guideline from the Journal of Urology recommends screening for pheochromocytoma with plasma or 24-hour urinary metanephrines in patients with adrenal incidentalomas that display ≥ 10 HU on non-contrast CT or who have signs/symptoms of catecholamine excess 1.
From the Research
Laboratory Workup for Pheochromocytoma
The laboratory workup for pheochromocytoma, a catecholamine-secreting tumor, involves several biochemical tests to establish the diagnosis. The following are the key tests used:
- Plasma free metanephrines: This test is considered the most sensitive and specific for diagnosing pheochromocytoma 2, 3.
- Urinary fractionated metanephrines: This test is also used to diagnose pheochromocytoma, especially when plasma free metanephrines are not available 4, 2.
- Urinary catecholamines: This test can be used to support the diagnosis of pheochromocytoma, but it has lower sensitivity and specificity compared to plasma free metanephrines and urinary fractionated metanephrines 5, 2.
- Urinary vanillylmandelic acid: This test has lower sensitivity and specificity compared to other tests and is not recommended as a first-line test 2.
Diagnostic Approach
The diagnostic approach for pheochromocytoma involves:
- Measuring plasma free metanephrines or urinary fractionated metanephrines as the initial biochemical test 4, 2.
- Using radiological imaging tests such as computed tomography (CT) or magnetic resonance imaging (MRI) to localize the tumor 4.
- Performing scintigraphy with (123)I-metaiodobenzylguanidine (MIBG) or positron emission tomography (PET) with (18)F-F-fluorodopamine (F-DA) for functional imaging 4.
- Considering genetic testing for patients with a family history of pheochromocytoma or multiple endocrine neoplasia type 2, von Hippel-Lindau syndrome, neurofibromatosis type 1, or familial paraganglioma 4.
Challenges and Limitations
The diagnosis of pheochromocytoma can be challenging due to:
- Borderline increased results in biochemical tests, which require follow-up testing to confirm or exclude the diagnosis 6.
- The low incidence of pheochromocytoma among the tested population, which can lead to false-positive results and unnecessary further testing 3.
- The need for a systematic approach to diagnosis, combining biochemical tests with radiological and functional imaging tests 4, 3.