Pheochromocytoma

Pheochromocytoma is a catecholamine-secreting tumor derived from the chromaffin cells of the adrenal medulla. The term pheochromocytoma refers to the appearance of the tumor cells on histological section after staining with chromium salts (phios means dark-colored, chromo means color, cytoma means tumor). Approximately 90 percent of pheochromocytomas reside entirely within the adrenal glands. The remainder may develop external to the gland in the paraganglion chromaffin tissue of the sympathetic nervous system. In such instances the tumors are referred to as an ex-tra-adrenal pheochromocytoma or, paraganglioma.

Pheochromocytomas secrete the catecholamines epinephrine (adrenaline) and norepinephrine (noradrenaline) and elevated plasma dopamine levels have been reported in some cases. Despite the fact that healthy adrenal chromaffin cells predominately secrete epinephrine, pheochromocytomas secrete norepinephrine in greater abundance. One exception is in the case of familial pheochromocytomas which tend to secrete more epinephrine. Nonetheless, excessive unregulated catecholamine secretion results in hyperstimulation of both α and β adrenergic receptors. This leads to sporadic episodes of life-threaten-ing hypertension, increases in cardiac contractility, cardiac arrhythmias, glycogenolysis, gluconeogenesis, and intestinal relaxation.

Pheochromocytoma is considered a rare disease. The prevalence of pheochromocytoma is estimated at 1 in 100,000 persons per year, and about 0.1 percent in patients with hypertension and 4 percent in patients with adrenal mass. Approximately 25 percent of these masses are discovered incidentally before symptoms arise. Incidence of pheochromocytoma is found equally in males and females, and is not specific to any ethnicity. It may occur in individuals of any age, although the peak incidence is between the third and fifth decade.

Patients with pheochromocytoma present with a history of episodic headaches, palpitations, and perfuse sweating, all associated with severe high blood pressure. Other symptoms may include feelings of anxiety or terror, tremor, nausea, and constipation is common. Pheochromocytoma is associated with several familial endocrine disorders characterized by multiple and varied tumors throughout a variety of endocrine, and neuroendocrine tissues. For example, pheochromocytoma is a constituent of the multiple endocrine neoplasia type IIa (MEN IIa), and type IIb (MEN IIb) syndromes. These conditions are almost invariably (95 percent) associated with genetic mutations in a gene—more specifically a proto-oncogene—named ret. The ret pro-to-oncogene encodes for a cell-surface protein called a tyrosine kinase. Abnormal tyrosine kinase activity may cause dysfunctional regulation of the cell life-cycle, and is known to contribute to a variety of cancerous conditions. In addition, there is evidence that pheochromocytoma is associated with the syndromes neurofibromatosis (von Recklinghausen disease), and von Hippel-Lindau (VHL) disease.

The physical findings of patients with pheochromocytoma are consistent with the known actions of catecholamines. These include, but are not limited to hypertension, hypertensive retinopathy, orthostatic hypotension, pallor, tremor, and abnormal cardiac rhythms. Other physical findings may include café au lait spots and neurofibromas. The symptoms are associated with surges of catecholamine secretion from the tumor that occur in spells of inconsistent timing and duration. It is not clearly [Page 1376]understood what mediates episodic catecholamine secretion, but some triggers include mechanical stimulation arising from intra-abdominal pressure during urination or defecation, childbirth, emotional distress, administration of anesthesia, and several classes of drugs that affect the autonomic nervous system.

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