Table 1. Major Genetic Syndromes That Carry an Increased Risk of Pheochromocytoma continued...
24-hour urine collection
A 24-hour urine collection for catecholamines (e.g., epinephrine, norepinephrine, and dopamine) and fractionated metanephrines (e.g., metanephrine and normetanephrine) has a relatively low sensitivity (77%-90%) but a high specificity (98%). Pretest probability is also important. The specificity of plasma-free fractionated metanephrines is 82% in patients tested for sporadic pheochromocytoma versus 96% in patients tested for hereditary pheochromocytoma.[25,26]
Plasma-free fractionated metanephrines
Measurement of plasma-free fractionated metanephrines appears to be an ideal case-detection test for patients at higher baseline risk of pheochromocytoma. Examples of these patients might include the following:
- Patients with an incidentally discovered adrenal mass.
- Patients with a family history of pheochromocytoma.
- Patients with a known inherited predisposition to pheochromocytoma.
The test is associated with a relatively high false-positive rate in patients with a lower baseline risk of pheochromocytoma. Measurement of plasma-free metanephrines (e.g., metanephrine and normetanephrine) has a high sensitivity (97%-99%) but a relatively low specificity (85%).
In general, it is reasonable to use measurement of plasma-free fractionated metanephrines for initial case detection, which is followed by 24-hour measurement of urine-fractionated metanephrines and catecholamines for confirmation. Test results can be difficult to interpret because of the possibility of false-positive results. False-positive results can be caused by any of the following:[20,25]
- Common medications (e.g., tricyclic antidepressants).
- Physical or emotional stress.
- Inappropriately low reference ranges based on normal laboratory data rather than clinical data sets.
- Common foods (e.g., caffeine and bananas) that interfere with specific assays and medications.
A mildly elevated catecholamine or metanephrine level is usually the result of assay interference caused by drugs or other factors. Patients with symptomatic pheochromocytoma almost always have increases in catecholamines or metanephrines two to three times higher than the upper limits of reference ranges.
Provocative testing (e.g., using glucagon) can be dangerous, adds no value to other current testing methods, and is not recommended.
Computed tomography (CT) imaging or magnetic resonance imaging (MRI) of the abdomen and pelvis (at least through the level of the aortic bifurcation) are the most commonly used methods for localization. Both have similar sensitivities (90%-100%) and specificities (70%-80%). CT imaging provides superior anatomic detail compared with MRI.