What is a pheochromocytoma?

Pheochromocytomas are a type of tumor of the adrenal glands that can release high levels of epinephrine and norepinephrine. As the name implies, the “ad-renal” glands are located near the "renal" area. In other words, the adrenal glands are small glands that are located near the top of the kidneys. One adrenal gland sits on top of each of the two kidneys. Despite their small size, the adrenal glands have many functions. They are complex endocrine (hormone secreting) glands. Cells in different regions of the adrenal glands have different functions in the endocrine system. There is an area (zona fasciculata) where the cells secrete cortisol, a hormone similar to cortisone. There is another area (zona glomerulosa) where cells secrete a hormone called aldosterone which helps in water regulation.

There is yet another area, referred to as the adrenal medulla, where the cells secrete substances called catecholamines -- epinephrine, norepinephrine and dopamine. These are "flight or fight" hormones. They are responsible in part for that feeling of an "adrenaline" rush people feel when they are afraid. It is these cells that are involved in a pheochromocytoma. Basically, a pheochromocytoma is a tumor of these catecholamine-secreting cells, and that causes the clinical signs and symptoms. The catecholamine-secreting cells are sometimes referred to as chromaffin cells, and they are found in other areas of the body as well as in the adrenal medulla.

Sometimes, Pheochromocytomas arise from chromaffin cells that are located outside of the adrenal gland. In this case, they are termed extra-adrenal pheochromocytomas or paragangliomas and are usually located in the abdomen. Pheochromocytomas may occur in persons of any age. The peak incidence is between the third and the fifth decades of life, but approximately 10% occur in children. Pheochromocytomas are, fortunately, quite rare and the majority of them are entirely benign. Only about 10% of pheochromocytomas are malignant.

What are the symptoms of a pheochromocytoma?

Someone with a pheochromocytoma usually has three classic symptoms:

• headache,
• sweating, and
• heart palpitations (a fast heart beat) in association with markedly elevated blood pressure (hypertension)

Other conditions that may accompany these classic symptoms are as follows:

• anxiety,
• nausea,
• tremors,
• weakness,
• abdominal pain, and
• weight loss

Some people, however, never develop symptoms of a pheochromocytoma. In some cases, the high blood pressure comes and goes and may be difficult to document. In other cases, the blood pressure is consistently elevated and easily recorded. Pheochromocytomas are present in only about 0.2% of all people with high blood pressure. There are certain conditions, however, in which the diagnosis of pheochromocytoma may rank high on the list of possibilities; they are discussed below.

What conditions are associated with pheochromocytomas?

Pheochromocytomas can be a component of certain familial or genetic syndromes. The most common familial condition is called multiple endocrine neoplasia or MEN for short. Two types of MEN -- MEN 2A and 2B -- are associated with pheochromocytomas. Both are genetic syndromes that run in families and are transmitted from parent to child in an autosomal dominant manner. Pheochromocytomas are not the only tumors that occur in MEN 2A and 2B. MEN 2A carries an increased risk of tumors of the parathyroids, glands near the thyroid that help to regulate calcium levels in the body. And both MEN 2A and 2B elevate the risk of thyroid cancer. In families where MEN is suspected, genetic testing can be done to help identify family members at risk.

Pheochromocytomas are a feature of other genetic disorders, including von Hippel-Lindau syndrome and neurofibromatosis. Both of these disorders are associated with the development of numerous benign and malignant tumors. There are also many individuals who have pheochromocytomas with no known family history of them. These cases are termed sporadic. In general, if these patients have bilateral disease (pheochromocytomas in both adrenal glands) or are diagnosed before the age of 21, genetic screening is recommended.

What else can cause the symptoms of a pheochromocytoma?

Basically, anything that can cause over activity of the sympathetic nervous system can be on the list of diagnoses to rule out when suspecting a pheochromocytoma. The sympathetic system is the main control panel governing the release of the "flight or fight" response in response to stress or fear, as mentioned above. Things that can stimulate this include drugs (even excessive use of decongestants should be considered); withdrawal from drugs (such as suddenly stopping certain blood pressure medications); panic attacks, and spinal cord injuries are among the many conditions that can also lead to some of the symptoms seen in pheochromocytomas.

How is pheochromocytoma diagnosed?

Pheochromocytoma is a possibility in anyone with the classic triad of symptoms:

• headache,
• sweating, and
• heart palpitations

Especially when there is high blood pressure (though high blood pressure is not always present), A physician becomes more suspicious if the patient is young and has no other risk factors or habits that may cause these findings.

Perhaps the patient knows their family history well and can inform their doctor of pheochromocytoma(s) diagnosed in family members. Consequently, a doctor suspecting familial pheochromocytoma can go straight to genetic testing. However, in most cases, if suspicion is high, the physician proceeds with a series of tests to measure the culprit hormones and their breakdown products (metabolites) listed below. First, hormones such as catecholamines and metanephrines are measured in a 24 hour urine collection, and metanephrines may also be measured in the blood. If these are greater than 2 times the normal level, imaging studies are usually done to look at the adrenal glands. If imaging with MRI or CT scans of the adrenal glands shows a mass in the gland (or outside it), surgery may be done. If it is not clear that the mass is actually functional and related to the findings clinically, or if there is no mass seen on imaging, another test can be performed. This test called a 131-I-MIBG scan is quite specific for pheochromocytomas. In this test a radioactive iodine molecule is injected into the bloodstream and localized in the area of the tumor, allowing visualization of the pheochromocytoma on imaging studies.

How is a pheochromocytoma treated?

Surgery is the definitive treatment. Until the tumor is removed, control of blood pressure is a top priority. Controlling blood pressure before and during surgery is the trickiest part of care. There is a chance of developing an acute hypertensive crisis after anesthesia is given during the surgery. The blood pressure is therefore closely monitored through the procedure. Consultation with an endocrinologist is recommended to help design treatment for individual patients.

Because of the types of hormones involved in a pheochromocytoma, blood pressure control utilizes agents of a specific class of drugs known as alpha blockers. There are also certain drugs (known as tyrosine kinase inhibitors) available which inhibit the formation of hormones by the tumor. These medications can be used if needed preoperatively. In the rare instances of pheochromocytomas that are malignant, chemotherapy or radiation therapy may be required after surgery.

What is the prognosis with a pheochromocytoma?

In general, pheochromocytomas that are confined to the adrenal gland are benign, and when removed by surgery have excellent outcomes. Patients with recurrent pheochromocytoma tumors, tumors that are metastatic or unable to be removed surgically have a fair to poor outlook. Pheochromocytoma in a pregnant patient (a rare occurrence), has a poor outcome for the mother and fetus; the mortality (death) rate is about 50% for both patients. Both malignant and benign pheochromocytomas can recur after surgery. The statistics vary from one study to the next, but recurrence rates average around 10%. Therefore, long-term follow-up care after surgery is very important to keep outlooks fair to good with additional appropriate treatments of medicine or surgery.

Pheochromocytoma at a Glance

• Pheochromocytoma is a relatively rare tumor of the adrenal glands or of similar specialized cells outside of the adrenal glands.
• Pheochromocytomas secrete catecholamine hormones (adrenaline and related hormones) that are responsible for the characteristic symptoms.
• Headache, sweating, and a fast heartbeat are typical symptoms, usually in association with markedly high blood pressure.
• About 10% of pheochromocytomas are malignant.
• Surgery is the treatment of choice.
• Pheochromocytomas can occur in combination with other tumors, conditions and in some familial (inherited) syndromes.