The University of Arizona
Department of Surgery
 

Pheochromocytoma

Overview

A pheochromocytoma is an adrenal gland (a pair of glands located just above the kidneys) tumor that overproduces hormones called catecholamines and can result in sudden and fatal cardiovascular events. (Examples of catecholamines are dopamine, norepinephrine, and epinephrine.) The annual incidence ranges from 2 to 8 cases per million persons. Pheochromocytomas account for 1% of surgically curable cases of hypertension (high blood pressure). Most pheochromocytomas were initially thought to occur sporadically (no family history), but new studies have shown that close to 30% of pheochromocytomas have a genetic component. Tumors that occur outside of the adrenal gland are referred to as paragangliomas. Most pheochromocytomas are benign (noncancerous), but 15% are malignant (cancerous).

Certain hereditary diseases are associated with pheochromocytomas or paragangliomas:

  • Multiple endocrine neoplasia type 2A and 2B
  • von Hippel-Lindau disease
  • Neurofibromatosis type 1
  • Familial paraganglioma syndrome

The most common clinical symptom of a pheochromocytoma is hypertension. The classic pattern of hypertension is an acute episode of severe high blood pressure that returns to normal. But in 50% of patients with a pheochromocytoma, blood pressure can remain persistently elevated, making it difficult to differentiate from essential (cause unknown) hypertension.

Other symptoms can occur during these paroxysms (sudden attack) of hypertension:

  • Headache
  • Anxiety
  • Sweating
  • Chest palpitations
  • Abdominal pain
  • Vision changes
  • Syncope (Fainting)
  • Nausea or vomiting

Several factors can induce these paroxysms, including exercise, sexual intercourse, defecation, alcohol intake and urination. The inherent danger of pheochromocytomas is that invasive procedures in untreated patients can result in extreme hypertension, cardiac arrhythmia's, myocardial infarction (heart attack), pulmonary edema (lung swelling due to excessive fluid), a cerebrovascular accident (stroke), seizures,  multiorgan failure (heart failure, respiratory failure, renal failure), or death.

Workup

The diagnosis can usually be confirmed with a 24-hour urine collection test for fractionated metanephrines (metanephrine, normetanephrine, total) and fractionated catecholamines (epinephrine, normetanephrine, total). This test has a 98% sensitivity and specificity rate. Note that iodine-containing contrast solution can falsely lower metanephrine levels; labetalol and alpha-methyldopa can falsely elevate catecholamine levels; and tricyclic antidepressants and renal insufficiency also interfere with test results.

Another test, for fractionated plasma-free metanephrines (metanephrine, normetanephrine) has a high sensitivity rate of 99%, but is not good for general screening because of a 10% false-positive rate. This test is best used when the suspicion for pheochromocytoma is high because of family history.

To localize the pheochromocytoma, these imaging tests are useful:

  • Computed tomography (CT)
  • Magnetic resonance imaging (MRI)
  • MIBG (metaiodobenzylguanidine) scanning, which is most valuable for identifying tumors that are bilateral (both sides) or that are not seen on CT or MRI

Care

For at least 2 weeks before surgery, patients should take an alpha-blocker such as phenoxybenzamine (at a starting dose of 10 mg twice a day, titrated to up to 160 mg daily until blood pressure is controlled and symptoms of orthostatic hypotension [low blood pressure when standing] occur). Side effects include nausea, nasal congestion, indigestion, and lassitude (weakness or exhaustion). Alternative medications include prazosin, doxazosin, and calcium channel blockers.

Surgery can be either a laparoscopic adrenalectomy (minimally invasive removal of the affected adrenal gland) or, for large tumors or those suspected to be malignant, an open (traditional) adrenalectomy.

Follow-up

To confirm complete resection (surgical removal of all tumor), patients need to undergo a 24-hour urine collection test 2 weeks after surgery, then annual screening with 24-hour urine or plasma fractionated metanephrines and catecholamines tests.

Prognosis

Patients with benign tumors have a great prognosis. Those with malignant tumors and metastasis (spread throughout the body) have a 5-year survival rate of 30% to 45%.
 

References
Grant CS. Pheochromocytoma. In: Clark OH, Duh QY, Kebebew E. 2nd ed. Textbook of Endocrine Surgery. Philadelphia, PA: Elsevier; 2005, pp. 621-631.
 
Young WF. Adrenal causes of hypertension: Pheochromocytoma and primary aldosteronism. Rev Endocr Metab Disord. 2007;8:309-320.