Pheochromocytoma 

A pheochromocytoma is a rare, catecholamine-secreting tumor derived from chromaffin cells. When such tumors arise outside of the adrenal gland, they are termed extra-adrenal pheochromocytomas, or paragangliomas. (See the images below.) Because of excessive catecholamine secretion, pheochromocytomas may precipitate life-threatening hypertension or cardiac arrhythmias. If the diagnosis of a pheochromocytoma is overlooked, the consequences can be disastrous, even fatal; however, if a pheochromocytoma is found, it is potentially curable.^[1] (See Pathophysiology, Prognosis, and Treatment.)

The term pheochromocytoma (in Greek, phios means dusky, chroma means color, and cytoma means tumor) refers to the color the tumor cells acquire when stained with chromium salts. Roux performed the first surgical resection of a pheochromocytoma in Lausanne, Switzerland in 1926. Later the same year, Charles Mayo performed the first surgical resection in the United States.^[2]

In a study by Paraby et al, severe hypertension was associated with 5 of 35 pheochromocytoma resections (14.3%), compared with 2 of 106 nonpheochromocytoma adrenal tumor resections (1.9%), and there was a significant increase in the need for intraoperative hypertensive treatment in the pheochromocytoma patients. In the study, the researchers investigated whether significant differences exist between perioperative hemodynamic changes arising from laparoscopic adrenalectomy for pheochromocytomas and those stemming from the use of the procedure for other types of adrenal tumors. The study included 34 patients who underwent laparoscopic adrenalectomy for pheochromocytomas (total resections = 35) and 104 patients who underwent the laparoscopic adrenalectomy for other tumors (total resections = 106).^[3] (See Treatment.)

Despite the greater occurrence of hypertension in the pheochromocytoma group, the investigators found no instances of transient or persistent systolic blood pressure of greater than 220 mm Hg in either group and noted no significant differences in recovery room hemodynamic parameters, frequency of persistent hypotension, or occurrence of heart rates greater than 120/min between the 2 groups.

Location of pheochromocytomas

Over 90% of pheochromocytomas are located within the adrenal glands, and 98% are within the abdomen. Extra-adrenal pheochromocytomas develop in the paraganglion chromaffin tissue of the sympathetic nervous system. They may occur anywhere from the base of the brain to the urinary bladder. Common locations for extra-adrenal pheochromocytomas include the organ of Zuckerkandl (close to origin of the inferior mesenteric artery), bladder wall, heart, mediastinum, and carotid and glomus jugulare bodies. (See Workup.)

Malignancy

Approximately 10% of pheochromocytomas are malignant. Direct invasion of surrounding tissue or the presence of metastases determines malignancy. Unfortunately, no other reliable clinical, biochemical, or histologic features distinguish a malignant from a benign pheochromocytoma. Factors that suggest a malignant course include large tumor size and DNA ploidy pattern (aneuploidy, tetraploidy). Common metastatic sites include bone, liver, and lymph nodes.

Patient education

For patient education information, see High Blood Pressure.

The clinical manifestations of a pheochromocytoma result from excessive catecholamine secretion by the tumor. Catecholamines typically secreted, either intermittently or continuously, include norepinephrine and epinephrine; rarely, dopamine is secreted. The biologic effects of catecholamines are well known. Stimulation of alpha-adrenergic receptors results in elevated blood pressure, increased cardiac contractility, glycogenolysis, gluconeogenesis, and intestinal relaxation. Stimulation of beta-adrenergic receptors results in an increase in heart rate and contractility.^[4]

Catecholamine secretion in pheochromocytomas is not regulated in the same manner as in healthy adrenal tissue. Unlike the healthy adrenal medulla, pheochromocytomas are not innervated, and catecholamine release is not precipitated by neural stimulation. The trigger for catecholamine release is unclear, but multiple mechanisms have been postulated, including direct pressure, medications, and changes in tumor blood flow.

Relative catecholamine levels also differ in pheochromocytomas. Most pheochromocytomas secrete norepinephrine predominantly, whereas secretions from the normal adrenal medulla are composed of roughly 85% epinephrine. Familial pheochromocytomas are an exception, because they secrete large amounts of epinephrine. Thus, the clinical manifestations of a familial pheochromocytoma differ from those of a sporadic pheochromocytoma.

Precipitants of hypertensive crisis

Precipitants of a hypertensive crisis include the following:

• Anesthesia induction
• Opiates
• Dopamine antagonists
• Cold medications
• Radiographic contrast media
• Drugs that inhibit catecholamine reuptake, such as tricyclic antidepressants and cocaine
• Childbirth

Occurrence in the United States

Pheochromocytomas are rare, reportedly occurring in 0.05-0.2% of hypertensive individuals. Patients may be completely asymptomatic. A retrospective study from the Mayo Clinic revealed that in 50% of cases, the diagnosis was made at autopsy.^[5] Approximately 10% of pheochromocytomas are discovered incidentally.^[6]

Race- and age-related demographics

Pheochromocytomas occur in people of all races, although they are diagnosed less frequently in blacks.

Pheochromocytomas may occur in persons of any age. The peak incidence, however, is between the third and the fifth decades of life. Approximately 10% occur in children. In children, 50% of pheochromocytomas are solitary intra-adrenal, 25% are present bilaterally, and 25% are extra-adrenal.

The 5-year survival rate for people with nonmalignant pheochromocytomas is greater than 95%. In those with malignant pheochromocytomas, the 5-year survival rate is less than 50%.

Although pheochromocytomas are rare, making the diagnosis is critical, because the malignancy rate is 10%, pheochromocytomas may be associated with a familial syndrome, they may precipitate life-threatening hypertension, and the patient may be cured completely with their removal.

Many cardiac manifestations are associated with pheochromocytomas. Hypertension is the most common complication. Cardiac arrhythmias, such as atrial and ventricular fibrillation, may occur because of excessive plasma catecholamine levels. Other complications include myocarditis, signs and symptoms of myocardial infarction,^[7] dilated cardiomyopathy, and pulmonary edema, either of cardiac or noncardiac origin.

A pheochromocytoma-induced hypertensive crisis may precipitate hypertensive encephalopathy, which is characterized by altered mental status, focal neurologic signs and symptoms, or seizures. Other neurologic complications include stroke due to cerebral infarction or an embolic event secondary to a mural thrombus from a dilated cardiomyopathy. Intracerebral hemorrhage also may occur, because of uncontrolled hypertension.

Pregnancy

Pheochromocytoma occurring during pregnancy carries a grave prognosis, with maternal and fetal mortality rates of 48% and 55%, respectively. However, maternal mortality is virtually eliminated and the fetal mortality rate is reduced to 15% if the diagnosis is made antenatally.