Pheochromocytoma is a rare tumor of chromaffin cells most commonly arising from the adrenal medulla. An estimated 800 cases are diagnosed yearly in the United States. The peak incidence is in the third to fifth decades of life. Bilateral disease is present in approximately 10% of patients. Bilaterality is much more common in familial pheochromocytoma and is often found in association with the familial multiple endocrine neoplasia syndromes (MEN, types 2A and 2B). In patients with MEN type 2 syndromes, the risk of developing a contralateral tumor following unilateral adrenalectomy is approximately 50%. Other syndromes associated with pheochromocytoma include neurofibromatosis, von Hippel-Lindau disease, cerebellar hemangioblastoma, Sturge-Weber syndrome, and tuberous sclerosis. In a series of 82 unselected patients with pheochromocytoma, 23% were found to be carriers of associated familial disorders. Therefore, all patients with pheochromocytomas should be screened for MEN2 and von Hippel-Lindau disease to avert further morbidity and mortality in the patients and their families. Extra-adrenal pheochromocytoma or functional paraganglioma occurs in approximately 10% to 15% of cases and may arise from any extra-adrenal chromaffin tissue in the body associated with sympathetic ganglia.
Extra-adrenal pheochromocytoma is most often located within the abdomen and may have greater malignant potential than adrenal pheochromocytoma.[3,4] Extra-adrenal tumors usually have a poorer prognosis than adrenal tumors.[3,4] In one series of 73 patients referred to tertiary care centers, however, no difference was found in the metastatic potential or the prognosis of extra-adrenal tumors compared to adrenal tumors. Because of the production and release of catecholamines, pheochromocytomas cause hypertension. Only 0.1% to 0.5% of all hypertension patients, however, will be found to have a pheochromocytoma. The importance of the recognition of this disease is that more than 90% of patients properly diagnosed and treated are curable.[4,6,7,8,9,10]
The hypertension caused by pheochromocytoma may be sustained or paroxysmal and is often severe with occasional malignant features of encephalopathy, retinopathy, and proteinuria. Less commonly, severe hypertensive reactions may occur during incidental surgery, following trauma, exercise, or micturition (in the setting of bladder pheochromocytoma) when the diagnosis is unsuspected. Other clinical features of pheochromocytoma include headache, sweating, palpitation, tachycardia, and severe anxiety along with epigastric or chest pain. Orthostatic hypotension is frequently present and is probably caused by reduced intravascular volume following chronic adrenergic stimulation.
The diagnosis of pheochromocytoma is established by the demonstration of elevated 24-hour urinary excretion of free catecholamines (norepinephrine and epinephrine) or catecholamine metabolites (vanillylmandelic acid and total metanephrines). The measurement of plasma catecholamines can also be of value in the diagnosis of pheochromocytoma. The measurement of plasma catecholamines, however, has limited sensitivity and specificity. Plasma metanephrines have been reported to be more sensitive than plasma catecholamines. When 52 patients with pheochromocytoma were studied, every patient was found to have elevated plasma levels of metanephrines, but eight of the patients had normal levels of plasma catecholamines. Pharmacologic testing with agents such as glucagon or clonidine is rarely required to make the diagnosis.[12,13]