Pheochromocytoma

Pheochromocytoma

Definition

Pheochromocytoma is a tumor of special cells (called chromaffin cells), most often found in the middle of the adrenal gland.

Description

Because pheochromocytomas arise from chromaffin cells, they are occasionally called chromaffin tumors. Most (90%) are benign tumors so they do not spread to other parts of the body. However, these tumors can cause many problems and if they are not treated and can result in death.

Pheochromocytomas can be found anywhere chromaffin cells are found. They may be found in the heart and in the area around the bladder, but most (90%) are found in the adrenal glands. Every individual has two adrenal glands that are located above the kidneys in the back of the abdomen. Each adrenal gland is made up of two parts: the outer part (called the adrenal cortex) and the inner part (called the adrenal medulla). Pheochromocytomas are found in the adrenal medulla. The adrenal medulla normally secretes two substances, or hormones, called norepinephrine and epinephrine. These two substances, when considered together, are known as adrenaline. Adrenaline is released from the adrenal gland, enters the bloodstream and helps to regulate many things in the body including blood pressure and heart rate. Pheochromocytomas cause the adrenal medulla to secrete too much adrenaline, which in turn causes high blood pressure. The high blood pressure usually causes the other symptoms of the disease.

Demographics

Pheochromocytomas are rare tumors. They have been reported in babies as young as 5 days old as well as adults as old as 92 years old. Although they can be found at any time during life, they usually occur in adults between 30-40 years of age. Pheochromocytomas are somewhat more common in women than in men.

Causes and symptoms

The cause of most pheochromocytomas is not known. A small minority (about 10-20%) of pheochromocytomas arise because a person has an inherited susceptibility to them. Inherited pheochromocytomas are associated with four separate syndromes: Multiple Endocrine Neoplasia, type 2A (MEN2A), Multiple Endocrine Neoplasia, type 2B (MEN2B), von Hippel-Lindau disease (VHL) and Neurofibromatosis type 1 (NF1).

Individuals with pheochromocytomas as part of any of these four syndromes usually have other medical conditions, as well. People with MEN2A often have cancer (usually thyroid cancer ) and other hormonal problems. Individuals with MEN2B can also have cancer and hormonal problems, but also have other abnormal physical features. Both MEN2A and MEN2B are due to genetic alterations or mutations in a gene called RET, found at chromosome 10q11.2. Individuals with VHL often have other benign tumors of the central nervous system and pancreas, and can sometimes have renal cell cancer. This syndrome is caused by a mutation in the VHL gene, found at chromosome 3p25-26. Individuals with NF1 often have neurofibromas (benign tumors of the peripheral nervous system). NF1 is caused by mutations in the NF1 gene, found at chromosome 17q11.

All of these disorders are inherited in an autosomal dominant inheritance pattern. With autosomal dominant inheritance, men and women are equally likely to inherit the syndrome. In addition, children of individuals with the disease are at 50% risk of inheriting it. Genetic testing is available for these four syndromes (MEN2A, MEN2B, VHL and NF1) but, due to the complexity, genetic counseling should be considered before testing.

Most people (90%) with pheochromocytoma have hypertension, or high blood pressure. The other symptoms of the disease are extremely variable. These symptoms usually occur in episodes (or attacks) called paroxysms and include:

• headaches
• excess sweating
• racing heart
• rapid breathing
• anxiety/nervousness
• nervous shaking
• pain in the lower chest or upper abdomen
• nausea
• heat intolerance

The episodes can occur as often as 25 times a day or, as infrequently as once every few months. They can last a few minutes, several hours or days. Usually, the attacks occur several times a week and last for about 15 minutes. After the episode is over, the person feels exhausted and fatigued.

Between the attacks, people with pheochromocytoma can experience the following:

• increased sweating
• cold hands and feet
• weight loss
• constipation

Diagnosis

If a pheochromocytoma is suspected, urine and/or a blood tests are usually recommended. A test called "24-hour urinary catacholamines and metanephrines" will be done. This test is designed to look for adrenaline and the break-down products of adrenaline. Since the body gets rid of these hormones in the urine, those testing will need to collect their urine for 24 hours. The laboratory will determine whether or not the levels of hormones are too high. This test is very good at making the diagnosis of pheochromocytoma. Another test called "serum catacholamines" measures the level of adrenaline compounds in the blood. It is not as sensitive as the 24-hour urine test, but can still provide some key information if it shows that the level of adrenaline compounds is too high.

One of the difficulties with these tests is that a person needs to have an attack of symptoms either during the 24-hour urine collection time period or shortly before the blood is drawn for a serum test to ensure the test's accuracy. If a person did not have an episode during that time, the test can be a "false negative." If a doctor suspects the patient has gotten a "false negative" test, additional tests called "pharmacologic tests" can be ordered. During these tests, a specific drug is given to the patient (usually through an IV) and the levels of hormones are monitored from the patient's blood. These types of tests are only done rarely.

Once a person has been diagnosed with a pheochromocytoma, he or she will undergo tests to identify exactly where in the body the tumor is located. The imaging techniques used are usually computed tomography scan (CT scan) and magnetic resonance imaging (MRI). A CT scan creates pictures of the interior of the body from computer-analyzed differences in x rays passing through the body. CT scans are performed at a hospital or clinic and take only a few minutes. An MRI is a computerized scanning method that creates pictures of the interior of the body using radio waves and a magnet. An MRI is usually performed at a hospital and takes about 30 minutes.

Treatment team

A pheochromocytoma will usually be treated by an internist (general medical doctor) an anesthesiologist (doctor who administers anesthesia for surgery) and a specialized surgeon (doctor who removes the tumor from the body). If the tumor is found to be malignant, a radiation oncologist (doctor who specializes in radiation treatment for cancer) and medical oncologist (doctor who specializes in chemotherapy treatment for cancer) may be consulted.

Clinical staging, treatments and prognosis

Once a pheochromocytoma is found, more tests will be done to see if the tumor is benign (not cancer) or malignant (cancer). If the tumor is malignant, tests will be done to see how far the cancer has spread. There is no accepted staging system for pheochromocytoma; but an observation of the tumor could provide one of these four indications:

• Localized benign pheochromocytoma means that the tumor is found only in one area, is not cancer, and cannot spread to other tissues of the body.
• Regional pheochromocytoma means that the tumor is malignant and has spread to the lymph nodes around the original cancer. Lymph nodes are small structures that are found all over the body that make and store infection-fighting cells.
• Metastatic pheochromocytoma means that the tumor is malignant and has spread to other, more distant parts of the body.
• Recurrent pheochromocytoma means that a malignant tumor that was removed has come back.

Treatment in all cases begins with surgical removal of the tumor. Before surgery, medications such as alpha-adrenergic blockers are given to block the effect of the hormones and normalize blood pressure. These medications are usually started 7 to 10 days prior to surgery. The surgery of choice is laparoscopic laparotomy, which is a minimally invasive outpatient abdominal procedure performed under general or local anesthesia. A small incision is made in the abdomen, the laparoscope is inserted and the tumor is removed. The patient can usually return to normal activities within two weeks. If a laparoscopic laparotomy cannot be done, a traditional laparotomy will be performed. This is a more invasive surgery done under spinal or general anesthesia and requires five to seven days in the hospital. Usually patients are able to return to normal activities after four weeks. After surgery, blood and urine tests will be done to make sure hormone levels return to normal. If the hormone levels are still above normal, it may mean that some tumor tissue was not removed. If not all tumor can be removed (as in malignant pheochromocytoma, for example) drugs will be given to control high blood pressure.

If a pheochromocytoma is malignant, radiation therapy and/or chemotherapy may be used. Radiation therapy uses high-energy x rays to kill cancer cells and shrink tumors. Because there is no evidence that radiation therapy is effective in the treatment of malignant pheochromocytoma, it is not often used for treatment. However, it is useful in the treatment of painful bone metastases if the tumor has spread to the bones. Chemotherapy uses drugs to kill cancer cells. Like radiation therapy, it has not been shown to be effective in the treatment of malignant pheochromocytoma. Chemotherapy, therefore, is only used in rare instances.

Untreated pheochromocytoma can be fatal due to complications of the high blood pressure. In the vast majority of cases, when the tumor is surgically removed, pheochromocytoma is cured. In the minority of cases (10%) where pheochromocytoma is malignant, prognosis depends on how far the cancer has spread, and the patient's age and general health. The overall median five-year survival from the initial time of surgery and diagnosis is approximately 43%.

Coping with cancer treatment

If laparascopic laparotomy is done and no further treatment is necessary, patients usually return to normal activity within two weeks. If more extensive surgery is performed, normal activity is delayed for a few weeks and can be emotionally difficult. In rare cases where radiation and/or chemotherapy are needed, coping can be very difficult. Consultation with physicians, nurses, social workers, and psychologists may be beneficial.

Prevention

Unfortunately, little is known about environmental and other causes of pheochromocytoma. Some of the tumors are due to inherited predisposition. Because of these factors, pheochromocytoma cannot be prevented.

Special concerns

Pheochromocytoma in children

Pheochromocytoma is rare in children, but occurs most commonly between the ages of 8 and 14 years. Diagnosis of pheochromocytoma can be more difficult at this age, because other childhood cancers (e.g. neuroblastoma ) can also elevate adrenaline compounds in the body. Pheochromocytomas in children are more likely to be bilateral (on both the left and right sides of the body) and outside the adrenal glands. For this reason, transabdominal surgery is usually performed to remove the tumor.

Pheochromocytoma in pregnancy

Although rare, pheochromocytoma in pregnancy can be very dangerous. Because x rays are to be avoided in pregnancy, MRI and/or ultrasound is used to locate the tumor. Alpha-adrenergic blocking agents to reduce blood pressure are given to the woman as soon as the diagnosis is made. If the woman is in the first two trimesters of pregnancy, most often the tumor is removed. In the third trimester, the woman usually remains on alpha-adrenergic blocking agents until a cesarean section can be safely performed.

See Also Multiple endocrine neoplasia syndromes; von Recklinghausen's neurofibromatosis

Resources

BOOKS

Keiser, Harry R. "Pheochromocytoma and Related Tumors.". In Endocrinology, Fourth Edition, edited by Leslie J DeG-root and J. Larry Jameson. New York: W.B. Saunders Company, 2001, pp1862-1883.

Goldfien, Alan. "Adrenal Medulla." In Basic and Clinical Endocrinology, edited by Francis Greenspan and David Gardner. New York: Lange Medical Books/McGraw-Hill, 2001, pp. 399-421.

PERIODICALS

Barzon, Luisa, and Marco Boscaro. "Diagnosis and Manage ment of Adrenal Incidentalomas." In The Journal of Urol ogy 163 (February 2000):398-407.

Young, William F. "Management Approaches to Adrenal Inci dentaloma". In Endocrinology and Metabolism Clinics of North America 29 (March 2000): 159-185.

Baker, Joanne. "Adrenal Disorders: A Primary Care Approach." In Lippincott's Primary Care Practice 1 (5) (November/December 1997): 527-536.

OTHER

"Pheochromocytoma" National Cancer Institute Cancer Web <http://www.graylab.ac.uk/cancernet/202494.html> 29 June 2001.

Lori De Milto

Kristen Mahoney Shannon, M.S., C.G.C.

KEY TERMS

Adrenal medulla

—The central core of the adrenal gland.

Laparoscope

—An instrument used to examine body cavities during certain types of surgery; for example, surgeries to remove fibroid tumors, or gall bladders, are often removed through the navel rather than cutting into the body.

Paroxysm

—A sudden attack of symptoms.