Table 1. Major Genetic Syndromes That Carry an Increased Risk of Pheochromocytoma continued...
Phenoxybenzamine (blocks alpha receptors) is an effective treatment for catecholamine excess and metyrosine (blocks catecholamine synthesis) can be added if needed.
Parasympathetic extra-adrenal paragangliomas do not secrete catecholamines and usually present as a neck mass with symptoms related to compression or are incidentally discovered on an imaging study performed for an unrelated reason. In addition, approximately half of patients with pheochromocytoma are asymptomatic because their neoplasms are discovered in the presymptomatic state by either abdominal imaging for other reasons (e.g., adrenal incidentalomas) or genetic testing in at-risk family members.[21,22,23,24]
The diagnosis of pheochromocytoma is usually suspected by the presence of an adrenal mass or a workup. Biochemical testing is done to document excess catecholamine secretion. Once the biochemical diagnosis of a catecholamine-secreting tumor is confirmed, localization studies should be performed. Controversy exists as to the optimal single test to make the diagnosis.
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.