Pheochromocytoma is a rare tumor that develops in the adrenal glands. There are two adrenal glands in the human body, which are located on top of the kidneys. Each adrenal gland has two parts, the outer cortex and inner medulla. The cortex produces corticosteroid and androgen hormones. The medulla produces catecholamines (epinephrine, norepinephrine, and dopamine).

Pheochromocytomas may be found in one or both glands and may spread, or metastasize (pronounced meh-TAS-tuh-size), beyond the adrenal glands. Pheochromocytomas develop from the center of the adrenal gland, in an area called the adrenal medulla, which secretes catecholamines.

Hormones that are normally produced by the adrenal medulla, catecholamines (pronounced kat-i-KOL-uh-meens), help to regulate heart rate, blood pressure, and the body's responses to stress. Pheochromocytomas release additional catecholamines, causing higher than normal amounts in the body. Changes in hormone levels produce some of the clinical signs and life-threatening symptoms of pheochromocytoma.

Although the majority of pheochromocytomas are benign (non-cancerous or non-metastatic), about one-third are malignant (cancerous or metastatic) and spread to other parts of the body. Malignant pheochromocytomas may spread, or metastasize, to the liver, lungs, bone, and lymph nodes.

Pheochromocytoma is a type of neuroendocrine tumor that grows from cells called chromaffin cells. These cells produce hormones needed for the body and are found in the adrenal glands. The adrenal glands are small organs located in the upper region of the abdomen on top of the kidneys. About 80-85% of pheochromocytomas grow in the inner layer of the adrenal gland, called the adrenal medulla. About 15-20% of pheochromocytomas grow outside of this area and are called extra-adrenal pheochromocytomas or paragangliomas.

Most pheochromocytomas are benign, which means they are not cancer and do not spread to other parts of the body. Only about 10% of pheochromocytomas spread to other parts of the body.

It is unknown how many people have pheochromocytoma because many people are never diagnosed. Most cases of pheochromocytoma occur in people aged 30 to 50 years old. One estimate suggests about only 8 people per 1 million people have pheochromocytoma, but this estimate may be low.

Approximately one-third of pheochromocytoma cases occur when patients inherit a mutated gene from their parents. Studies have linked several genes to the disease, but researchers are not sure how these genes contribute to the formation of this tumor.

The remaining two-thirds of cases are spontaneous and are not associated with a family history. However, genetic inheritance may play a role in the development of the disease through unknown genes. For example, in one study, a significant percentage of patients (7.5% to 27%) with sporadic pheochromocytoma had genetic mutations that have been linked to other family-inherited syndromes.

Scientists have found mutations in approximately 20 different genes that they think may lead to pheochromocytoma and paraganglioma. Mutations in the genes RET, VHL, NF1, SDHA, SDHB, SDHC, SDHD, SDHAF2, MDH2, IDH1, PHD1/PHD2, HIF2A/EPAS1/2, TMEM127, MAX, HRAS, MAML3 and CSDE1 may play a role in forming pheochromocytoma and paragangliomas. In many cases, it is not known what causes pheochromocytoma to form.

If you have pheochromocytoma, you may have other genetic conditions that increased your chance of getting pheochromocytoma. These genetic conditions include:
• Multiple endocrine neoplasia 2 syndrome, types A and B (MEN2A and MEN2B)
• Von Hippel-Lindau (VHL) syndrome
• Neurofibromatosis type 1 (NF1)
• Hereditary paraganglioma syndrome
• Carney-Stratakis dyad (paraganglioma and gastrointestinal stromal tumor [GIST])
• Carney triad (paraganglioma, GIST, and pulmonary chondroma)

In some cases, pheochromocytoma can run in families. About 25-35% of cases of pheochromocytoma may be inherited. Some of these inherited cases may be associated with a genetic condition, such as Multiple Endocrine Neoplasia Types 2a and 2b, Von Hippel-Lindau Syndrome, and Neurofibromatosis.

Disease screening should be offered to presymptomatic relatives who have a diagnosed mutation, especially because familial syndromes are also associated with other types of tumors and early diagnosis improves the prognosis of these patients. Patients with known genetic mutations should undergo regular periodic screening with biochemical testing and anatomic imaging (CT or MRI scans) to rule out the presence of disease.

Pheochromocytoma causes a variety of signs and symptoms, including (in alphabetical order):

• Abdominal pain
• Constipation
• Chest pain
• Dizziness
• Elevated blood sugar
• Facial flushing (redness)
• High blood pressure
• Increased respiratory rate
• Nausea
• Nervousness, anxiety, and irritability
• Pale skin tone
• Rapid heart rate and heart palpitations
• Severe headaches
• Sweating
• Visual disturbances
• Weight loss

A health care provider uses blood and urine tests that measure catecholamines (pronounced kat-i-KOL-uh-meens) and/or their metabolites to diagnose pheochromocytoma. Metabolites are biochemical substances that form when another is broken down in the body. Higher than normal amounts of these biochemical substances in the blood and/or urine can be an indication of the presence of a pheochromocytoma/paraganglioma.

Pheochromocytomas can secrete all, none, or any combination of catecholamines (epinephrine, norepinephrine, dopamine) and their metabolites, which are called metanephrines (metanephrine, normetanephrine, methoxytyramine). Multiple studies at the National Institutes of Health (NIH) have demonstrated the utility of measuring metanephrines in the blood for the diagnosis of pheochromocytoma/paraganglioma. This method is often recommended as the first diagnostic test when there is suspicion for a pheochromocytoma/paraganglioma.

Tumors can also be found accidentally during non-related imaging studies. The location of a pheochromocytoma can be determined by using several imaging methods, including computed tomography (CT) and magnetic resonance imaging (MRI). CT scans use X-rays to produce detailed images of the inside of the body, while MRI uses magnetic waves to produce these pictures. A third imaging method that can be used to detect pheochromocytomas is MIBG (metaiodobenzylguanidine) scintigraphy. During this procedure, MIBG, a compound containing a small amount of radioactivity, is injected into a vein and is picked up by pheochromocytoma cells, but not normal cells. The body is scanned with a scanner that detects the MIBG. Any MIBG that is seen with the scanner can indicate the presence of pheochromocytoma cells.

Pheochromocytoma can occur at any age. However, it is diagnosed most frequently between the ages of 30 and 50.

Up to 20% of pheochromocytomas are diagnosed in children.

Yes. Genetic testing is available for pheochromocytoma. Genetic testing is especially recommended for some groups of patients who:

• Have a family history of pheochromocytoma
• Have clinical features of syndromes associated with pheochromocytoma
• Have multiple tumors or an extra-adrenal tumor (tumor is at a location other than the adrenal glands) (paraganglioma)
• Are diagnosed before age 50
• Have specific biochemical results

Genetic testing may also be recommended for other patients depending upon family history, the patient's age, and the location of the patient's tumor.

Standard treatments for pheochromocytoma include:

• Surgical removal of the tumor
• Medications (chemotherapy) designed to kill tumor cells
• Radiotherapy: utilizing radio waves to destroy the tumors
• Medications to control the signs and symptoms of the disease

Types of Therapies for Pheochromocytoma:

Ninety percent of patients are cured by surgery to remove benign pheochromocytoma tumors. Surgery for tumor removal is typically done by laparoscopy, during which a small incision is made in the abdomen. During surgery to remove the tumor, the physician will usually examine nearby organs to determine whether the pheochromocytoma has spread to other parts of the body.

Medications are prescribed to treat the clinical signs and symptoms of pheochromocytoma.

Commonly prescribed medications include the following:

• Alpha-adrenergic blockers to lower blood pressure
• Beta blockers for controlling rapid, irregular pulse

For tumors that are successfully removed, blood pressure and hormone levels usually return to normal over the weeks immediately following surgery.

The success of pheochromocytoma treatment depends upon several factors; the most important include: presence of metastasis, genetics, location, and overall extent of the disease. Malignant pheochromocytoma can only be determined by the presence of metastasis or tumor spreading (tumors in locations such as the bone, liver, lungs, or lymph nodes).

The only curative treatment for pheochromocytoma is complete surgical removal of the tumor. The long-term prognosis of patients after resection of a single sporadic pheochromocytoma is excellent.

Even after tumor removal, there is still a risk that pheochomocytoma or paraganglioma might return (called recurrence). Recurrence is more likely for those with paraganglioma, those who are younger, those whose family members also have the disease, and those who had large tumors.

There is currently no cure for malignant pheochromocytoma. Radiation therapy, or the use of radio waves to destroy tumors, can assist in shrinking some malignant tumors. Tumor shrinkage can lessen the clinical signs and symptoms of pheochromocytoma by reducing the production of hormones and in some cases may allow for surgery.

Although not curative, medications are used to control the clinical signs and symptoms of both benign and malignant pheochromocytoma.

The estimate of how a disease will affect you long-term is called prognosis. Every person is different and prognosis will depend on many factors, such as:

• Where the tumor is in your body
• If the cancer has spread to other parts of your body
• How much of the tumor was taken out during surgery

If you want information on your prognosis, it is important to talk to your doctor.

Doctors estimate pheochromocytoma survival rates by how groups of people with pheochromocytoma have done in the past. Patients with a small pheochromocytoma that has not spread to other parts of the body have a five-year survival rate of about 95%. Patients with pheochromocytoma that has grown back (recurred) or spread to other parts of the body have a five-year survival rate between 34% and 60%.

Pheochromocytoma can be inherited as part of another syndrome or may coexist with other diseases. Some patients with pheochromocytoma have the inheritable disease von Hippel-Lindau (VHL) syndrome or neurofibromatosis type 1 (NF1). Both VHL and NF1 are cancer syndromes in which patients have tumors at multiple sites.

Another disease in which pheochromocytoma is often present is multiple endocrine neoplasia type 2 (MEN2), which produces tumors in the endocrine glands, including the parathyroid gland. About one-half of patients with MEN2 have pheochromocytoma.

Approximately one-third of pheochromocytoma cases are inheritable, and the remaining cases occur sporadically. Children are at risk of developing pheochromocytoma/paraganglioma if they inherit one of the known disease-causing mutated genes from their parents. The penetrance of the disease, or the percentage of individuals with a known genetic mutation who develop the disease, varies with different mutations.

Pregnancy may be complicated by the clinical signs of pheochromocytoma. In pregnant women, high blood pressure, cardiovascular problems, and seizures, which occur in patients with pheochromocytoma, could affect the health of the unborn child.