Pheochromocytoma

What is pheochromocytoma?

A pheochromocytoma (pronounced FEE-oh-KROH-moh-sy-TOH-muh) is a rare tumor that forms in the center of one or both of your adrenal glands (adrenal medulla). The tumor is made of a certain type of cell called a chromaffin cell, which produce and release the hormones that cause the “fight or flight” response.

Usually, pheochromocytoma affects only one adrenal gland, but it can affect both glands. Sometimes there’s more than one tumor in one adrenal gland.

Most pheochromocytomas are benign (not cancerous). Approximately 10% to 15% of pheochromocytomas may be malignant (cancerous). There's no standard staging system for pheochromocytoma if it’s cancerous. Instead, it’s described as the following:

• Localized pheochromocytoma: The tumor is in one or both adrenal glands only.
• Regional pheochromocytoma: The cancer has spread to lymph nodes or other tissues near your adrenal glands.
• Metastatic pheochromocytoma: The cancer has spread to other parts of your body, like your liver, lungs, bone or distant lymph nodes.
• Recurrent pheochromocytoma: The cancer has recurred (come back) after it has been treated. It may come back in the same place or in another part of your body.

What are adrenal glands?

You have two adrenal glands, one on top of each kidney in the back of your upper abdomen. They are part of your endocrine system. Each adrenal gland has two parts. The outer layer of your adrenal gland is called your adrenal cortex. The center of your adrenal gland is called your adrenal medulla.

Your adrenal medullae make hormones called catecholamines that help regulate the following important bodily functions and aspects:

• Heart rate.
• Blood pressure.
• Blood sugar (blood glucose).
• The way your body responds to stress (the “fight or flight” response).

The primary catecholamines include:

• Dopamine.
• Epinephrine (adrenaline).
• Norepinephrine (noradrenaline).

Sometimes a pheochromocytoma can release extra adrenaline and noradrenaline into your blood, causing certain symptoms.

What is the difference between pheochromocytoma and paraganglioma?

Pheochromocytoma and paraganglioma are both rare tumors that come from the same type of cells known as chromaffin cells.

Pheochromocytoma is a tumor that forms in the center of your adrenal gland (adrenal medulla), and paragangliomas form outside your adrenal gland.

Who gets a pheochromocytoma?

Anyone at any age can get a pheochromocytoma, but they occur most often in people between 30 and 50 years of age. Approximately 10% of cases occur in children.

How common are pheochromocytomas?

Pheochromocytomas are rare tumors. The true number of pheochromocytoma cases is unknown since many people with pheochromocytomas don’t have symptoms and go undiagnosed. Less than 1% of people who have high blood pressure have a pheochromocytoma.

What are the symptoms of pheochromocytoma?

Signs and symptoms of pheochromocytoma happen when the tumor releases too much adrenaline (epinephrine) or noradrenaline (norepinephrine) into your blood. However, some pheochromocytoma tumors don’t make extra adrenaline or noradrenaline and don’t cause symptoms (are asymptomatic).

Common symptoms of pheochromocytoma include:

• High blood pressure (hypertension).
• Headache.
• Excessive sweating for no known reason.
• A pounding, fast or irregular heartbeat.
• Feeling shaky.

Less common symptoms of pheochromocytoma include:

• Pain in your chest and/or abdomen.
• Being much paler than usual.
• Nausea and/or vomiting.
• Diarrhea.
• Constipation.
• An extreme drop in blood pressure upon standing suddenly (orthostatic hypotension).
• Unexplained weight loss.

You may experience signs and symptoms of pheochromocytoma after certain events, including:

• Intense physical activity.
• A physical injury or intense emotional stress.
• Childbirth.
• Going under anesthesia.
• Surgery.
• Eating foods high in tyramine, like red wine, chocolate and cheese.

Can symptoms of pheochromocytoma come and go?

A person with a pheochromocytoma could have sustained high blood pressure (the most common symptom of pheochromocytoma) or it may come and go.

People with pheochromocytomas may also experience paroxysmal “attacks,” which are chronic episodes of high blood pressure that often lead to headaches, irregular heartbeats (palpitations) and excessive sweating (diaphoresis). These episodes can happen anywhere from several times a day to a couple of times a month.

What causes pheochromocytoma?

In most cases of pheochromocytoma, the exact cause is unknown, and it occurs randomly.

Approximately 25% to 35% of people who have pheochromocytoma have a hereditary condition (passed through the family) that’s linked to pheochromocytoma, including:

• Multiple endocrine neoplasia 2 syndrome, types A and B (MEN2A and MEN2B).
• Von Hippel-Lindau (VHL) disease.
• Neurofibromatosis type 1 (NF1).
• Hereditary paraganglioma syndrome.
• Carney-Stratakis dyad [paraganglioma and gastrointestinal stromal tumor (GIST)].
• Carney triad (paraganglioma, GIST and pulmonary chondroma).

Pheochromocytomas may also be caused by mutations (changes) of one of at least 10 different genes.

How is pheochromocytoma diagnosed?

Since pheochromocytoma is a rare tumor and is sometimes asymptomatic, it can be difficult to diagnose. Healthcare providers sometimes find pheochromocytomas when a test or procedure is done for another reason.

A healthcare provider may suspect a diagnosis of pheochromocytoma after reviewing the following factors:

• A detailed medical history, including previous pheochromocytoma cases in your family.
• A thorough physical and medical evaluation.
• Certain symptom characteristics, such as paroxysmal attacks and high blood pressure that’s unresponsive to standard treatment.

What tests are used to diagnose pheochromocytoma?

Your healthcare provider may use the following tests and procedures to diagnose pheochromocytoma:

• 24-hour urine test: This type of urine (pee) test involves collecting your urine for 24 hours to measure the level of catecholamines (adrenal hormones) in your urine. Substances that result from the breakdown of these hormones are also measured. Higher-than-normal amounts of certain catecholamines in your urine may be a sign of pheochromocytoma.
• Blood catecholamine tests: These tests measure the level of catecholamines in your blood. Substances that result from the breakdown of these hormones are also measured. Higher-than-normal levels of certain catecholamines in your blood may be a sign of pheochromocytoma.
• CT scan (computer tomography scan): A CT scan is an imaging procedure that takes a series of X-ray images from different angles to provide detailed pictures of areas inside your body. Your provider may recommend a CT scan so that they can look at your adrenal glands.
• MRI (magnetic resonance imaging): An MRI is an imaging procedure that uses a magnet, radio waves and a computer to make a series of detailed pictures of areas inside your body. Your provider may recommend an MRI so that they can look at your adrenal glands.

After your provider has diagnosed pheochromocytoma, they’ll likely perform additional tests to see if the tumor is benign or malignant and if it has spread to other parts of your body.

Is there genetic testing for pheochromocytoma?

If you’re diagnosed with pheochromocytoma, your provider may recommend genetic counseling to find out your risk for having an inherited syndrome and other related cancers.

Your healthcare provider may recommend genetic testing if any of the following situations apply to you:

• You have a personal or family history of traits linked with inherited pheochromocytoma or paraganglioma syndrome.
• You have tumors in both of your adrenal glands.
• You have more than one tumor in one adrenal gland.
• You have signs or symptoms of higher-than-normal catecholamine levels in your blood.
• You’ve been diagnosed with pheochromocytoma before age 40.

If your genetic counselor finds certain gene changes in your testing results, they'll likely recommend that your family members who are at risk but do not have signs or symptoms be tested as well.

How is pheochromocytoma treated?

The best treatment option is surgery, when feasible.

Treatment options for pheochromocytoma depend on several factors, including:

• The size of the tumor.
• If the tumor is benign (not cancer) or malignant (cancer).
• If you have symptoms of catecholamines that are higher than normal.
• If the tumor is in one area only or has spread to other places in your body (metastasized).
• If the tumor has been diagnosed for the first time or has come back (recurred).

If you have pheochromocytoma that causes symptoms due to excess adrenal hormones, your healthcare provider will likely recommend medication to manage the symptoms. Medications may include:

• Medication that keeps your blood pressure normal, such as alpha-blockers.
• Medication that keeps your heart rate normal, such as beta-blockers.
• Medication that blocks the effect of the excess hormones released by your adrenal gland(s).

Treatment options for pheochromocytoma include:

• Surgery.
• Radiation therapy.
• Chemotherapy.
• Ablation therapy.
• Embolization therapy.
• Targeted therapy.

Together, you and your healthcare team will determine a treatment plan that works best for you and your situation.

Surgery

Surgery is the main form of treatment for pheochromocytoma. Approximately 90% of pheochromocytomas are successfully removed by surgery.

If you have a pheochromocytoma, your provider may recommend a type of surgery called adrenalectomy to remove one or both of your adrenal glands. During the surgery, your surgeon will check the surrounding tissue and lymph nodes to see if the tumor has spread. If it has, your surgeon will remove the affected tissue(s) as well, if possible.

After surgery, your provider will check the catecholamine levels in your blood or urine. Normal catecholamine levels are a sign that all the pheochromocytoma cells were removed.

If your surgeon removes both of your adrenal glands, you’ll need life-long hormone therapy to replace hormones made by your adrenal glands.

Radiation therapy

Radiation therapy is a cancer treatment that focuses strong beams of energy to destroy cancer cells or keep them from growing while sparing as much surrounding healthy tissue as possible.

There are two types of radiation therapy:

• External radiation therapy: This therapy uses a machine outside your body to send radiation toward the cancer.
• Internal radiation therapy: This therapy uses a radioactive substance sealed in needles, seeds, wires or catheters that a healthcare provider places directly into or near the cancer.

The type of radiation therapy your provider may recommend depends on whether your cancer is localized, regional, metastatic or recurrent. Providers most often use external radiation therapy and/or 131I-MIBG therapy to treat malignant pheochromocytoma. 131I-MIBG is a radioactive substance infusion that collects in certain kinds of tumor cells, killing them with the radiation that it gives off.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells by killing the cells or by preventing them from dividing and multiplying. Chemotherapy is usually given intravenously through a vein (intravenously). It’s usually an effective treatment, but it can cause side effects.

Ablation therapy

Ablation therapy is a minimally invasive treatment option that uses very high or very low temperatures to destroy tumors. Ablation therapies that can help kill cancer cells and abnormal cells include:

• Radiofrequency ablation: This therapy uses radio waves to heat and destroy cancer cells and abnormal cells. The radio waves travel through electrodes (small devices that carry electricity).
• Cryoablation: This therapy uses liquid nitrogen or liquid carbon dioxide to freeze and destroy cancer cells and abnormal cells.

Embolization therapy

Embolization therapy is a pheochromocytoma treatment that blocks the artery leading to your adrenal gland. Blocking the blood flow to your adrenal glands helps kill the cancer cells that are growing there.

Targeted therapy

Targeted therapy is a treatment option that uses medications or other substances to attack specific cancer cells without harming healthy cells. Healthcare providers use targeted therapies to treat metastatic and recurrent pheochromocytoma.

Researchers are currently studying sunitinib, a type of tyrosine kinase inhibitor, for the treatment of metastatic pheochromocytoma. Tyrosine kinase inhibitor therapy is a type of targeted therapy that prevents tumors from growing.

Can I prevent pheochromocytoma?

Unfortunately, you can’t prevent developing a pheochromocytoma. However, if you’re at risk for developing a pheochromocytoma due to certain inherited syndromes and genes, genetic counseling can help screen for pheochromocytoma and potentially help you catch it in its early phases.

Talk to your healthcare provider if you have any first-degree relatives (siblings and parents) that have been diagnosed with pheochromocytoma and/or any of the following genetic conditions:

• Multiple endocrine neoplasia 2 syndrome.
• Von Hippel-Lindau (VHL) disease.
• Neurofibromatosis type 1 (NF1).
• Hereditary paraganglioma syndrome.
• Carney-Stratakis dyad.
• Carney triad.

What is the prognosis (outlook) for pheochromocytoma?

The prognosis (outlook) for pheochromocytoma is usually good if it’s treated. Approximately 90% of pheochromocytomas are successfully removed by surgery.

If pheochromocytomas are left untreated, they can potentially cause serious, life-threatening complications, including:

• Heart muscle disease (cardiomyopathy).
• Inflammation of your heart muscle (myocarditis).
• Uncontrolled bleeding in your brain (cerebral hemorrhaging).
• Accumulation of fluid in your lungs (pulmonary edema).

Some people with a pheochromocytoma may also be at risk of developing a stroke or heart attack (myocardial infarction).

When should I see my healthcare provider?

If you’ve been diagnosed with a pheochromocytoma and are experiencing concerning symptoms, contact your healthcare provider.

If you’re experiencing symptoms of pheochromocytoma, such as high blood pressure and headaches, talk to your provider. Even though pheochromocytoma is rare and the likelihood of having it is low, it’s important to treat high blood pressure.

If you’ve recently found out that one of your first-degree relatives (siblings and parents) has a genetic syndrome, such as multiple endocrine neoplasia 2 syndrome or von Hippel-Lindau (VHL) disease, that puts you at a higher risk of developing pheochromocytoma. You should contact your provider about genetic testing.

What questions should I ask my doctor?

If you’ve been diagnosed with a pheochromocytoma, it may be helpful to ask your healthcare provider the following questions:

• What caused my pheochromocytoma?
• Could my children and/or relatives develop a pheochromocytoma?
• What are my treatment options?
• What are the side effects of different treatment therapies?
• How can I manage my symptoms?

A note from Cleveland Clinic

Pheochromocytoma is a rare tumor. The good news is that it’s often benign and treatable. While most pheochromocytoma cases have an unknown cause, there’s a significant link to certain inherited conditions. If you or one of your first-degree relatives have been diagnosed with a pheochromocytoma, it’s important to go through genetic testing to make sure you don’t have a genetic condition that could potentially cause other medical issues. If you have any questions about your risk of developing a pheochromocytoma, talk to your healthcare provider. They’re there to help you.