Many clinicians use the term pheochromocytoma to refer to both adrenal pheochromocytomas and extra-adrenal catecholamine-secreting paragangliomas, because they have similar clinical presentations and are treated with similar approaches. The distinction between pheochromocytoma and paraganglioma is an important one, however, because of implications for associated neoplasms, risk of malignancy, and genetic testing.
Catecholamine-secreting tumors are rare, with an annual incidence of 2 to 8 cases per 1 million people in all populations studied. There are several reasons to suspect, confirm, localize, and resect these tumors:
Pheochromocytoma is frequently diagnosed before symptoms develop because of genetic screening for hereditary endocrine syndromes or incidental discovery of an adrenal mass on computed tomography (CT) or magnetic resonance imaging (MRI).
Approximately 5% of all adrenal incidentalomas have proved to be pheochromocytomas. In the past, more than 95% of patients with pheochromocytoma had paroxysmal symptoms (spells) of palpitations, diaphoresis, and headaches. With the widespread use of CT and MRI, however, approximately 50% of all pheochromocytomas are initially detected as adrenal incidentalomas in patients without spells and, frequently, without hypertension.
In a patient with spells, the degree of increase in fractionated metanephrines and catecholamines in the blood or urine should be markedly abnormal (eg, increases more than 5 times the upper limit of the reference range). In an asymptomatic patient with pheochromocytoma, however, the biochemical test results may be normal because the neoplasm has been detected in the prebiochemical phase. In this situation, the clinician must rely on the features of the mass on CT or MRI (the imaging phenotype) to guide management.
Plasma-fractionated metanephrines have a 15% false-positive rate, usually because of increased plasma normetanephrine concentrations. Table 1 shows the upper limits of the reference ranges based on patients who are investigated for pheochromocytoma but are found not to have this rare tumor.
|Table 1. Upper Limit of Reference Ranges for 24-Hour Urinary Fractionated Metanephrines and Catecholamines|
Patients with values above these diagnostic cutoffs have pheochromocytoma, are severely ill (eg, hospitalized in an intensive care unit), or are taking a medication that is causing false-positive test results. Use of antihypertensive agents (eg, b-adrenergic blockers, a-adrenergic inhibitors) and selective serotonin reuptake inhibitors does not result in false-positive biochemical test results.
|Table 2. Medications and Situations That Can Cause False-Positive Results on Biochemical Testing for Pheochromocytoma|
After biochemical confirmation of pheochromocytoma, CT or MRI of the abdomen and pelvis is the first localization test. Approximately 90% of these tumors can be localized when in the adrenal glands and 98% when in the abdomen and pelvis. If the abdominal imaging result is negative, then scintigraphic localization with 123I-metaiodobenzylguanidine (123I-MIBG) is indicated. Computer-assisted chest, neck, and head imaging provides additional localizing procedures that can be used, although they are rarely required.
The tumor can always be found in symptomatic patients with pheochromocytoma, because the average diameter of a pheochromocytoma in this situation is 4.5 cm. The typical imaging phenotype of a pheochromocytoma is a dense (Hounsfield units, >20) and vascular mass with slow contrast washout (<50% at 10 minutes after contrast medium administration).
By comparison, the much more common adrenocortical adenoma is usually hypodense (Hounsfield units, <10) and has rapid contrast washout (>50% at 10 minutes).
When the clinician has trouble localizing a pheochromocytoma, it is usually because the patient does not have pheochromocytoma. Medication-induced false-positive biochemical test results and use of inappropriately low reference ranges can lead to imaging misadventures.
Finally, it is important to understand that 123I-MIBG is taken up by healthy adrenal glands and the intensity of uptake is usually asymmetric. An adrenal gland should never be resected on the basis of asymmetric adrenal uptake of 123I-MIBG unless the uptake pattern correlates with a vascular adrenal mass on CT.