All About Pheochromocytoma

What are pheochromocytomas?

Pheochromocytomas are very rare tumors of chromaffin cells. Chromaffin cells are found in the adrenal gland and make hormones called catecholamines. In pheochromocytoma, the cells make too many catecholamines, like norepinephrine, epinephrine (also known as adrenaline), and dopamine. They are all needed for the body to work. Pheochromocytomas are found in the adrenal glands. Humans have two adrenals and each sits on top of a kidney. Often, only one adrenal gland is affected by a pheochromocytoma, but there may be more than one tumor in that gland.

Tumors that are found outside the adrenal glands are known as extra-adrenal pheochromocytomas or paragangliomas. Most tumors that start in the chromaffin cells do not spread to other parts of the body and are benign (not cancerous). Despite being benign, these tumors can cause problems because they make catecholamines. They do need to be treated. A small percent of pheochromocytomas are malignant (cancerous). These are tumors that have spread outside the adrenal gland.

What causes pheochromocytoma and am I at risk?

Pheochromocytoma is rare. There are about 2 to 8 persons per million diagnosed each year. It can affect a person of any age, affects men and women equally, and is most common in people ages 30 to 50. The only known risk factor is a genetic syndrome, which causes about 25% of cases. Genetic syndromes linked to pheochromocytoma are von Hippel-Lindau Syndrome (vHL), Multiple Endocrine Neoplasia Syndrome type 2A and 2B (MEN2A and 2B), Neurofibromatosis type 1 (NF1), and Succinate dehydrogenase syndromes. Talk to your provider about genetic testing and counseling if you think you should be tested for these syndromes.

How can I prevent pheochromocytoma?

There are no specific ways you can prevent pheochromocytoma. The only known risk factor is hereditary and you cannot change your genetics.

What screening tests are there for pheochromocytoma?

Pheochromocytoma is a very rare type of cancer and there are no specific screening tests.

What are the signs of pheochromocytomas?

The signs of a pheochromocytoma are related to the extra catecholamines being made. They can cause the classic symptoms of high blood pressure, along with headache, heart palpitations, and sweating. These symptoms can be persistent or can occur in "episodes,” with periods of time where there are no symptoms. How often you have side effects depends on how the tumor is causing catecholamines to be released into the bloodstream.  

Hypertension is the most common sign. Your blood pressure may be normal in between elevated episodes or unable to be controlled with medications. Some patients will present in "pheo crisis,” when adrenaline is released in a dangerous amount and can cause stroke, heart attack, organ failure, coma, and in some cases death.

How is pheochromocytoma diagnosed?

In some cases, it is found during a CT or MRI of the abdomen that was done for an unrelated reason. In patients who do have symptoms, there are blood and urine tests (such as a 24-hour urine collection) to measure the level of catecholamines in the body. Types of catecholamines tested for include vanillylmandelic acid, metanephrines, and plasma metanephrines. These are all substances that are formed as catecholamines are broken down by the body and higher if you have a pheochromocytoma.

CT and MRI scans are most often used to detect the tumor. A special nuclear medicine scan called a meta-iodo-benzylguanidine (MIBG) scan may be used in cases where the laboratory tests or symptoms point to a pheochromocytoma, but none is found on CT or MRI. This test uses a radioactive form of iodine, which is attached to the MIBG molecule. MIBG is structurally similar to noradrenaline. It is given through a vein. The patient returns to the nuclear medicine department the following day for the actual scan. This delay allows the MIBG compound to concentrate in any tumor cells. The radioactive part of the compound allows these areas of tumor to be seen on the scan. In addition, PET scanning is being studied in the diagnosis of these tumors. Genetic testing may be done if you are at risk of having an inherited syndrome.

How is pheochromocytoma staged?

After you have been diagnosed with pheochromocytoma, tests will be done to see if the tumor has spread to other parts of the body. Staging helps to guide your treatment and looks at where your tumor is and if it has spread.

The staging system used to describe pheochromocytoma is the "TNM system,” as described by the American Joint Committee on Cancer. The TNM systems are used to describe many types of cancers. They have three parts:

• T-describes the size/location/extent of the "primary" tumor in the lung.
• N-describes if the cancer has spread to the lymph nodes.
• M-describes if the cancer has spread to other organs (metastases). 

The staging system is very complex. The entire staging system is outlined at the end of this article. Though complicated, the staging system helps healthcare providers determine the extent of the cancer, and in turn, make treatment decisions for your cancer.

If standard staging is not used for your pheochromocytoma it may be called localized, regional, or metastatic:

• Localized: The tumor is found at an early stage in the adrenal medulla or in 1 or both adrenal glands. 
• Regional: Cancer has spread to surrounding tissues and/or lymph nodes. 
• Metastatic: Cancer has spread to a distant part of the body. 

How is pheochromocytoma treated?

There are different ways to treat your pheochromocytoma depending on if it is cancerous, if it has metastasized, and your overall health. There is limited research about treatments, but many options are available. Ask your provider what options are best for you. 

Surgical Treatment

Surgery is often used whether the tumor is benign or malignant. The surgical resection may remove the whole tumor and adrenal gland or the tumor and only part of the adrenal gland. If the cancer has spread to other parts of the body, those organs and tissues may also be removed. 

After the tumor is removed, symptoms often go away. Medication is used to treat hypertension before surgery and to prevent any issues during the surgery. Catecholamine levels can change quickly during the surgery and will need to be managed. The surgery should be done by providers with experience treating pheochromocytomas. A few weeks after surgery plasma free metanephrines (a laboratory test) are measured. If the results are normal, the resection is thought to be complete.

Surgical resection can often cure the cancer in cases of localized pheochromocytoma. These tumors may metastasize (spread) to the lung, brain, and bone. If it occurs, metastatic disease tends to progress slowly over a period of many years. There can be issues related to the elevated catecholamine levels which your provider will watch for. If both adrenal glands are removed a patient will need hormone replacement therapy.

Radiation Therapy

Radiation therapy uses high-energy x-rays to kill cancer cells. These x-rays are like those used for x-rays, but they are of a much higher energy. The high energy of x-rays in radiation therapy damages the DNA of cells. Cancer cells divide faster than healthy cells, so their DNA is more likely to be damaged than normal cells. It is harder for cancer cells to repair damaged DNA compared to normal cells, so cancer cells are killed more easily by radiation. Radiation therapy aims to kill cancer cells, while killing fewer cells in normal, healthy tissue. External beam radiotherapy can be used for patients who have malignant (metastatic) pheochromocytoma which has spread to the bone. The goal is to ease symptoms such as pain. The dose and how many treatments you get will depend on the treatment site and other patient factors.

Metaiodobenzylguanidine (MIBG), sometimes used to diagnose pheochromocytoma, can be used to treat malignant disease. Iodine-131 is used as a treatment. When given in a low dose, MIBG concentrates in areas of tumor, causing it to “light up” on a diagnostic scan. In higher doses, using iodine-131 MIBG, the radioactive iodine kills the cells that take up the MIBG. The treatment process involves an IV infusion of MIBG. Because radiation is emitted during and after the treatment, patients must stay within a certain area for a few days, until radiation levels in the body have dropped to the point where it is safe to leave. The treatment is well tolerated, but it can slow your body making blood cells by the bone marrow. Blood counts will need to be checked. After treatment, you will have another MIBG scan. If the treatment worked, there will be less MIBG uptake on the scan. There are some malignant pheochromocytomas which do not take up MIBG and in these tumors Iodine-131-MIBG therapy will not work. A test will be done prior to treatment to check if this type of therapy will work. Another medication that can be used is called iobenguane.

Peptide receptor radionuclide therapy (PRRT) combines a medication that targets cancer cells with a radioactive substance. This delivers radiation directly to the cancer cells. The medication used is lutetium Lu 177 dotatate. This is often given with other medications, and you will likely go home after treatment. 

Chemotherapy and Targeted Therapy

Chemotherapy are medications that are often given intravenously (IV, into a vein) or in pill form. Chemotherapy travels through the bloodstream and throughout the body to kill cancer cells. In the case of pheochromocytoma, chemotherapy is not used as a primary treatment, but as an option for symptomatic malignant pheochromocytoma that has not responded to MIBG therapy. The most often used chemotherapy regimen is cyclophosphamide, vincristine, and dacarbazine. Another medication that can be used is temodar. Similar to pre-surgical medical management with medication, patients being treated with chemotherapy need to have their hypertension treated. Chemotherapy can cause catecholamine release leading to high blood pressure.

Targeted therapies work by stopping or slowing the growth of a tumor by interfering with a specific molecule needed for cancer growth. Finally, newer treatments, including molecular-targeted therapies, such as sunitinib, are being studied in patients with malignant pheochromocytoma.

Clinical Trials

There are clinical research trials for most types of cancer, and every stage of the disease. Clinical trials are designed to determine the value of specific treatments. Trials are often designed to treat a certain stage of cancer, either as the first form of treatment offered, or as an option for treatment after other treatments have failed to work. They can be used to evaluate medications or treatments to prevent cancer, detect it earlier, or help manage side effects. Clinical trials are extremely important in furthering our knowledge of this disease. It is through clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your provider about participating in clinical trials in your area. You can also explore currently open clinical trials using the OncoLink Clinical Trials Matching Service.

Follow-Up Care and Survivorship

The guidelines for follow-up after treatment depends upon how you were treated. Your providers will create a follow-up plan for you. If you had surgery, you will likely have to see your provider to have testing done about 2 weeks after surgery. Most patients will see their providers about every 3-4 months for 2-3 years and then less often the longer you do not have recurrence of disease. You should look for symptoms that you had before such as high blood pressure and headaches. The levels of hormones in your blood will be watched. It is important to talk to your provider if you are having any recurrent or new side effects or symptoms so that your provider can determine the best testing, imaging, and plan of care.

Fear of recurrence, the financial impact of cancer treatment, employment issues, and coping strategies are common emotional and practical issues experienced by pheochromocytoma survivors. Your healthcare team can identify resources for support and management of these practical and emotional challenges faced during and after cancer.

Cancer survivorship is a relatively new focus of oncology care. With nearly 17 million cancer survivors in the US alone, there is a need to help patients transition from active treatment to survivorship. What happens next, how do you get back to normal, what should you know and do to live healthy going forward? A survivorship care plan can be a first step in educating yourself about navigating life after cancer and helping you communicate knowledgeably with your healthcare providers. Create a survivorship care plan today on OncoLink.

Resources for More Information

Pheochromocytoma Support Foundation

The Pheochromocytoma Support Foundation’s mission is to raise public awareness, provide information, and support those with pheochromocytoma and their families.

www.pheosupportfoundation.org

Cancer Hope Network

Provides one-on-one support to people undergoing treatment for cancer and to their families through training individuals who have recovered from cancer and matching them with cancer patients currently undergoing a similar experience

www.cancerhopenetwork.org

Cancer Support Community

An international non-profit dedicated to providing support, education and hope to people affected by cancer.

www.cancersupportcommunity.org

Appendix: Eight Edition of AJCC Staging Guidelines for Pheochromocytoma (PCC)