1

What is a pheochromocytoma?

A pheochromocytoma is a tumor of neuroendocrine tissue arising in the adrenal medulla from chromaffin cells that synthesize catecholamines. Neoplastic proliferation of these cells can lead to release of one or more substances (norepinephrine, epinephrine, or dopamine) in varying amounts and can cause catecholamine toxicity. Most pheochromocytomas are solitary, benign, and sporadic, but they are occasionally multifocal, malignant, or part of a syndrome (e.g., multiple endocrine neoplasias, von Hippel–Lindau syndrome, neurofibromatosis, tuberous sclerosis, Sturge-Weber syndrome, ataxia-telangiectasia). They can also occur in pediatric and obstetric settings. Similar tumors can arise in extraadrenal locations from paraganglial cells of the autonomic nervous system (e.g., in the organ of Zuckerkandl or carotid body) and in the heart or pericardium. These paragangliomas are less likely to be functional compared with adrenal tumors. Incidence of pheochromocytoma in the United States is approximately 1000 cases per year.

2

What are the signs and symptoms and diagnostic criteria?

Signs and symptoms of pheochromocytoma are related to catecholamine excess and vary, depending on which catecholamine predominates. Norepinephrine secretion is most common and is usually sustained, with effects related to α-adrenergic stimulation. Epinephrine release is less common and more often paroxysmal, causing episodic effects related to β-adrenoreceptor stimulation. Dopamine release is least common and has less specific signs and symptoms. Table 30-1 lists typical signs and symptoms as well as uncommon but more severe end-organ manifestations of catecholamine toxicity.

Catecholamine release (and symptoms) from the tumor may be provoked by postural changes, exercise, anxiety, trauma, or pain. Foods and medications (e.g., antidepressants, cold/flu medications, weight-loss medications, cocaine, tobacco, alcohol) may also exacerbate symptoms by their effects on catecholamine metabolism. Pheochromocytoma may first manifest during anesthesia and surgery for another related tumor or unrelated condition or during pregnancy and may be confused with other conditions such as thyrotoxicosis, malignant hyperthermia, or preeclampsia.

Diagnosis of pheochromocytoma is made by laboratory testing in patients with suggestive signs and symptoms. Elevated levels of metanephrine and normetanephrine measured in plasma (for patients with sustained signs and symptoms) or 24-hour urine collection (for patients with paroxysmal signs and symptoms) confirm the diagnosis. Absolute catecholamine concentrations may not always correlate with the severity of signs and symptoms because of temporal variation, difference in the predominant catecholamine, and adrenoreceptor desensitization that may occur with chronic exposure. Computed tomography, magnetic resonance imaging, metaiodobenzylguanidine scintiscan, or 18F-fluorodopa positron emission tomography scanning can be used for tumor localization and surgical planning. Before surgical intervention, echocardiography may be performed to detect cardiomyopathy and monitor improvement after preoperative medical therapy.