The term pheochromocytoma refers to a tumor, usually but not always located in the adrenal medulla, which secretes excessive amounts of catecholamines. The word combines the color (“dusky” from the Greek “phaios”) that catecholamines render the tissues in which they occur when exposed to dichromium salts (chromo) with the tissue type (cytoma=tumor). Pheochromocytoma is relatively rare, with an estimated occurrence of 1 in 1700–4500 individuals and 3–8 new cases per million people per year. It is found in 0.1–1% of patients with hypertension and 5% of patients in whom adrenal masses are discovered incidentally. The average age of diagnosis is 25 years in hereditary cases (approximately 20% of the total) and 44 years in sporadic (nonhereditary) cases. The genders are equally represented in the patient population. Although rare, the tumor is a dangerous one as the result of lack of detection and treatment is often fatal.
The signs and symptoms of the presence of a pheochromocytoma are listed in Table 1 and reflect fairly closely the known actions of the catecholamines summarized in Figure 1. The signs and symptoms are presented as characteristic of either the episodic spells of their appearance or their underlying constant (chronic) presence. The episodic symptoms occur as spells that may be spontaneous or brought about by a change in posture, anxiety, or certain medications. Spells may occur several times a day or as infrequently as once every few months; they are usually 15–20 minutes in duration, although they can be much longer or much shorter. It should be noted that most people who have such spells do not have a pheochromocytoma, as there are many other causes for these relatively nonspecific manifestations.
Table1. Signs and Symptoms of Pheochromocytoma
Fig1. Catecholamine-mediated responses to acute stress. Three types of responses are shown: On the left (pink) are effects of epinephrine on the heart and vasculature which allow increased blood flow to skeletal muscles and decreased flow to the GI tract. In the center (blue) is bronchodilation to allow increased gas exchange, thus maintaining the flow of oxygen to the muscles and brain. On the right (green) are the metabolic responses which increase the supply of fuel to the muscles and brain. In each box, the primary adrenergic receptor responsible for the actions is indicated.
The most sensitive and specific biochemical test for pheochromocytoma is the measurement of plasma or urinary free (nonconjugated) metanephrine and normetanephrine (Figure 2). These are produced continually by the pheochromocytoma itself, independent of catecholamine release, and there fore are a good marker of the presence of these cells. Once biochemical confirmation of a catecholamine- secreting tumor has been indicated, imaging studies can determine its localization so that it can be surgically resected. Most (85%) of the tumors will be found in the adrenal glands although some might lie elsewhere in the abdominal cavity, as will the catecholamine-secreting paragangliomas, which are also detected by metanephrine and normetanephrine measurements.
Fig2. Catabolism of circulating epinephrine and norepinephrine. Epinephrine and norepinephrine are inactivated in the liver, through the action of one or both of two enzymes, monamine oxidase (MAO) and catechol-O-methyltransferase (COMT). The latter uses S-adenosyl methionine as the methyl group donor. The metabolites shown on the right are excreted in the urine as glucuronide or sulfate conjugates.
Surgical removal is the sole treatment for pheochromocytoma and requires great care prior to and during the operation. Preparation involves the control of blood pressure for a period of time (about two weeks) prior to surgery and prevention of a hypertensive cri sis due to sudden catecholamine release from the tumor during surgery. Drugs used in this context are α- and β-blockers as well as inhibitors of tyrosine hydroxylase. In addition, anesthetics must be chosen carefully for their safety since some can affect catecholamine release; clearly, cardiovascular and hemodynamic parameters must be closely monitored.
