Pheochromocytomas are chromaffin cell tumors located in the adrenal medulla or extra-adrenal sites of the sympathetic nervous system (sympathetic chain, aortic arch, diaphragm, spleen, kidney, Zuckerkandl body, bladder wall, ovary and testis) which produce excessive amounts of catecholamines. Extraadrenal tumors are called paragangliomas. Pheochromocytomas and paragangliomas are characterized by the symptomatic triad of episodic sweating, headaches and palpitations in patients with either sustained or intermittent hypertension although symptoms can be variable. Catecholamine induced constriction of the arterial and venous vascular beds results in a decreased plasma volume and postural hypotension in norepinephrine dominant cases. These tumors occur in 0.1% of patients with diastolic hypertension and present most commonly in the fourth through the sixth decades of life. The ten percent rule states that 10% are malignant, 10% are bilateral, 10% are extra-adrenal and 10% are multiple. With paragangliomas, the malignancy rate increases to approximately 30%. Conditions associated with pheochromocytomas include multiple endocrine neoplasias types II and III, neurofibromatosis, medullary thyroid carcinoma and von Hippel-Lindau disease. Consider the diagnosis in cases where: there is a rise in blood pressure with antihypertensives (especially beta-blockers and guanethidine); worsening hypertension in response to anesthesia, naloxone, metoclopramide, tricyclic antidepressants, micturition, or pregnancy; a suprarenal incidentaloma on abdominal CT scanning, and refractory or severe hypertension. Common lab abnormalities may include hypokalemia, mild hypernatremia, hypomagnesemia, metabolic alkalosis and hyperglycemia. Hyperglycemia is secondary to increased glycolysis and inhibition of insulin release.

Pheochromocytomas can produce any of a vast list of products but most commonly produce epinephrine, norepinephrine or dopamine. Epinephrine is produced by 50-70% and norepinephrine is produced by 75-85% of pheochromocytomas.

The initial step in the workup is to show elevated levels of catecholamines. The diagnosis may be confirmed by measuring metanephrines and fractionated catecholamines in a 24 hour urine sample and a random resting plasma sample, respectively. Plasma catecholamine levels greater than 2,000 pg/mL and urinary metanephrine levels greater than 1.8 mg/day are highly suggestive of the diagnosis. Indeterminate levels are plasma catecholamine levels between 1,000 and 2,000 ng/mL and urinary metanephrine levels between 1.3 and 1.8 mg/day.  Indeterminate cases may have a pheochromocytoma or neurogenically mediated catecholamine release and require an oral clonidine suppression test for further clarification. Suppression of the plasma catecholamine level by 50% or more after clonidine therapy is indicative of neurogenically mediated catecholamine release whereas levels will be unaffected in cases of pheochromocytoma. If the urinary catecholamines are greater than 80% norepinephrine, then this is suggestive of an extra-adrenal tumor.

Once elevation of urinary catecholamines or metanephrines is confirmed, then localization of the tumor is the next step. CT and MRI are good initial tests for localization. If CT or MRI does not localize the tumor, the I-metaiodobenzylguanidine (131I-MIBG) scanning is a helpful test for localization.  If imaging techniques fail to reveal the location of the tumor, then adrenal venous blood sampling or angiography may be necessary.

While performing the workup or awaiting surgery, blood pressure control may be achieved with phenoxybenzamine (10 - 40 mg PO BID) as patients need to be asymptomatic for one week prior to surgery. If phenoxybenzamine is ineffective, a number of second line agents may be added to include: phentolamine, metyrosine or the peripheral alpha blockers. In patients with heart rates greater then 110 bpm after phenoxybenzamine therapy, a history of arrhythmias or PVCs, or with tumors that secrete predominantly epinephrine, then beta blocker therapy is indicated. Before surgery, patients may require liberal salt and fluid intake as they are volume constricted.

Once the tumor is localized, resection is indicated. Resection is not always curative for the hypertension. Approximately 40% of patients continue to be hypertensive postoperatively and require medical management. Also, tumor recurrence does occur, and postoperative patients should be screened for recurrence. Appropriate patients should undergo evaluation for associated MEN II or III and for von Hippel-Lindau disease.