A pheochromocytoma (fee-o- kroe-moe- sy-TOE- muh) is a rare, usually noncancerous (benign), slow-growing tumor that develops in cells in the center of an adrenal gland. You have two adrenal glands, one above each kidney. Your adrenal glands produce hormones that give instructions to virtually every organ and tissue in your body.
Pheochromocytoma is characterized by the presence of an excess amount of catecholamine hormone (defined by 1,2-dihydroxybenzene group-not methylated hydroxyl groups), which include norepinephrine (noradrenaline), epinephrine (adrenaline), and dopamine. If you have a pheochromocytoma, the tumor releases hormones that can cause persistent or episodic high blood pressure and other symptoms. If left untreated, a pheochromocytoma can result in severe or life-threatening damage to other body systems, especially the cardiovascular system.
Pheochromocytoma, if detected early, can be successfully treated and managed in the vast majority of cases. If possible, the treatment of choice for the condition is surgery to remove the tumor(s), but there are other treatment options. Surgical treatment usually returns blood pressure to normal. Once diagnosed, it is recommended to be seen by a multi-disciplinary medical team with pheo para experience and to talk to your doctor about genetic testing.
See the National Cancer Institutes Patient Guide to pheochromoctyoma.
Go to our Research Articles page for the most recently published research on pheochromocytoma.
signs to look for
Pheochromocytoma can occur at any age, but most commonly affects people between the ages of 20 and 50. While very rare, pheochromocytoma often causes a range of symptoms that when recognized can help with diagnosis. If you experience the symptoms below, you should see a doctor to get an accurate diagnosis, as many of these symptoms can be caused by multiple other conditions as well.
These signs and symptoms usually occur in brief spells of 15 to 20 minutes. Spells can happen several times a day or less often. Your blood pressure may be within the normal range or remain elevated between spells.
Signs + Symptoms
Triggers of Symptomatic Spells
When to see a Doctor
Signs + Symptoms
Signs or symptoms of pheochromocytomas may include:
- High blood pressure
- Rapid or forceful heartbeat
- Profound sweating without any reason
- Severe, throbbing headache
- Paleness in the face
- Shortness of breath
- Sensation of panic
Less common signs or symptoms may include:
- Anxiety or sense of doom
- Abdominal pain
- Weight loss
Triggers of Symptomatic Spells
Spells may occur spontaneously or may be triggered by such factors as:
- Physical exertion
- Anxiety or stress
- Changes in body position
- Bowel movement
- Labor and delivery
- Surgery and anesthesia
- Certain drugs such as steroids, decongestants, psychiatric drugs such as phenelzine, tranylcypromine, and isocarboxazid
Foods high in tyramine, a substance that affects blood pressure, also can trigger a spell. Tyramine is common in foods that are fermented, aged, pickled, cured, overripe or spoiled. These foods include:
- Some cheeses
- Some beers and wines
- Dried or smoked meats
- Avocados, bananas and fava beans
- Pickled fish
- Sauerkraut or kimchi
Certain medications that can trigger a symptomatic spell include:
- Monoamine oxidase inhibitors (MAOIs), such as phenelzine (Nardil), tranylcypromine (Parnate) and isocarboxazid (Marplan)
- Stimulants, such as amphetamines or cocaine
When to see a Doctor
The signs and symptoms of pheochromocytoma can be caused by a number of different conditions.
Although high blood pressure is a primary sign of a pheochromocytoma, most people with high blood pressure don’t have a pheochromocytoma, and not all patients with a pheochromocytoma have hypertension. It is common for pheo para patients to experience spells where symptoms arise quickly and intensely. Talk to your doctor if any of the following factors are relevant to you:
- Difficulty controlling high blood pressure with current treatment plan
- A family history of pheochromocytoma
- A family history of a related genetic disorder: multiple endocrine neoplasia, type II (MEN II); von Hippel-Lindau disease; familial paraganglioma or neurofibromatosis 1 (NF1)
preparing for your appointment
If a pheo is suspected, you should be referred to a doctor who specializes in hormonal disorders (an endocrinologist).
What you can do
Before your appointment, make a list that includes the following:
- Signs or symptoms — or any changes from normal— that may be causing concern
- A record of the frequency and duration of symptoms
- Recent changes or stresses in your life
- All medications — including over-the- counter drugs and dietary supplements — and doses you take. This is very important because supplements and OTC drugs can affect test results. Always consult your doctor before stopping medications.
- A log of typical food and beverage consumption
- Family history of medical conditions
Tests that examine the blood and urine are used to detect (find) and diagnose pheochromocytoma.
The following tests and procedures may be used:
The twenty-four hour urine and blood catecholamine tests are commonly used first if pheo para is suspected.
It is suggested to avoid coffee, tea, bananas, cocoa, citrus fruits, and vanilla for several days before being tested because these foods can cause higher than normal catecholamine levels.
Twenty-four-hour urine test:
A test in which urine is collected for 24 hours to measure the amounts of catecholamine in the urine. Substances caused by the breakdown of these catecholamines are also measured. An unusual (higher or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that makes it. Higher-than-normal amounts of certain catecholamines may be a sign of pheochromocytoma.
Blood catecholamine studies:
A procedure in which a blood sample is checked to measure the amount of certain catecholamines released into the blood. Substances caused by the breakdown of these catecholamines are also measured. An unusual (higher than or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that makes it. Higher-than-normal amounts of certain catecholamines may be a sign of pheochromocytoma.
This test compared to the 24-hour urine test can be more convenient since it includes only a one-time blood draw. It should be noted that the Endocrine Society Guidelines suggest that blood be drawn after the patient has a brief rest and is supine (lying down on his/her back). Patients with pheochromocytoma often have 2-4 times the normal range, so retesting in the supine position can be requested if you have indeterminate results.
Other biochemical tests:
The 24-hour urine test and the blood plasma test are the most common to help diagnose pheo para, but other biochemical tests can be used to diagnose/monitor.
Biochemical tests used for diagnosis of pheochromocytomas and paragangliomas include measurements in blood or urine of the catecholamines and various breakdown products (metabolites) of the catecholamines. Normetanephrine and metanephrine, are commonly referred to in the plural form as the “metanephrines”. Some laboratories also measure methoxytyramine, which is the breakdown product of dopamine. Another biochemical test still offered by some laboratories involves measurements in urine of vanillymandelic acid (commonly referred to as VMA), which represents the final major breakdown product of both noradrenaline and adrenaline. Measurements of plasma chromogranin A (CgA) is another test sometimes used.
SOURCE: Graeme Eisenhofer PhD, Professor & Chief, Division of Clinical
Neurochemistry, Institute of Clinical Chemistry & Laboratory Medicine
and Department of Medicine, University Hospital Dresden, Dresden, Germany
Once the above tests indicate a pheo or para, imaging, outlined below, is often used to identify where, how many, and size of the tumor(s).
Sometimes these imaging techniques involve the use of molecular imaging (using radiation to take pictures of the body). Molecular imaging and nuclear medicine (using radiation to treat an illness) can be confusing. The Society of Nuclear Medicine and Molecular Imaging has many online resources to explain the use of both and address issues about radiation exposure.
CT scan (CAT scan) :
A procedure that makes a series of detailed pictures of areas inside the body, such as the neck, chest, abdomen, and pelvis, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
MRI (magnetic resonance imaging):
A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body such as the neck, chest, abdomen, and pelvis. This procedure is also called nuclear magnetic resonance imaging (NMRI).
Functional imaging allows physicians to see how the body is functioning and to measure its chemical and biological processes. For pheo paras, functional imaging may include 123I-MIBG, 18F-FDG-PET/CT, 18F-DOPA-PET/CT or 68GaDOTATATE PET/CT scan. A small amount of radiopharmaceuticals are injected into the patient and detected by special types of cameras that work with computers to provide very precise pictures of the area of the body being imaged. Functional imaging can be used to identify if a disease has progressed to other parts of the body (metastatic), and where the tumors are located. Recent research has indicated that 68GaDOTATATE PET/CT scan can be especially effective at imaging metastatic disease. The cost of these scans can be prohibitive, they are not widely available, and they may not be covered by insurance.
exploring your options
Pheochromocytoma, if detected early, can be successfully treated and managed in the vast majority of cases. The treatment of choice for the condition is to surgically remove the tumor. Chemotherapy or radiotherapy are also treatment options in some cases and there are clinical trials ongoing as well. However, if left untreated, the tumor is likely to be fatal due to high blood pressure, heart failure, stroke, arrhythmias, or metastatic disease (where the cancer spreads to other organs or bones).
Below details treatment options as presented at the 2019 Pheo Para Conference. To see the full video, click on the links below.
Slide credit: Dr. Joseph Dillon
Somatostatin Analogs (SSA's)
Tyrosine kinase inhibitor therapy
Surgery to remove a pheochromocytoma may be done laproscopically or robotically, which is less invasive or by making a larger incision, if necessary. Sparing as much of the adrenal gland(s) is preferred. An adrenalectomy is to be avoided if possible to avoid life-long complications related to adrenal insufficiency. Also during surgery, the tissues and lymph nodes inside the abdomen will be checked and if the tumor has spread, these tissues may also be removed. Drugs may be given before, during, and after surgery to keep blood pressure and heart rate normal.
After surgery to remove the tumor, catecholamine levels in the blood or urine are checked. Normal catecholamine levels are a sign that all the pheochromocytoma cells were removed.
Before undergoing any surgical procedure, the patient must be adequately “blocked” with medication. The main goal of the administration of these medications is to normalize blood pressure and heart rate and to protect the patient from the effects of high levels of hormones (catecholamines) released during surgery. This usually involves taking an alpha blocking medication for at least 2 weeks before the surgery and monitoring the patient’s blood pressure carefully. The most common medication for alpha blocking patients is Phenoxybenzamine (Dibenzyline). Other alpha blocking medications can be used as well, sometimes in combination with calcium channel blockers. A beta-blocker may also be used in conjunction.
Going under anesthesia without being blocked is highly dangerous. The anesthesia drugs can have a negative influence on the tumors and cause them to release massive amounts of catecholamines. Manipulation of the tumor during surgery can also cause this release, which may result in a hypertensive crisis and even death. It is extremely important that the practitioners involved in the care of the patient have experience with pheochromocytoma/paraganglioma surgery and that patients be “blocked” for the best possible outcome.
It is not recommended for patients to have a biopsy of the tumor.
After Surgery: Follow-Up
A pheochromocytoma urine test and/or plasma tests should be repeated 4-8 weeks after surgery to check for any remaining disease. Long-term regular follow-up is recommended for all patients. Yearly urine or plasma tests for pheochromocytoma should be performed for life to detect remaining disease, return of the disease, or the development of metastases. For most people, follow-up CT or MRI is not needed if urine and plasma test results are normal unless a genetic cause was identified.
Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy:
- External radiation therapy uses a machine outside the body to send radiation toward the cancer.
- Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer.
The way radiation therapy is given depends on the type of cancer being treated and whether it is localized, regional, metastatic, or recurrent.
The use of molecular imaging (using radiation to take pictures of the body) and nuclear medicine (using radiation to treat an illness) can be confusing. The Society of Nuclear Medicine and Molecular Imaging has many online resources to explain the use of both and address issues about radiation exposure.
Pheochromocytoma can be treated with MIBG, which is a therapy that is injected into the patient’s bloodstream. It travels to and binds to the tumor delivering a targeted high dose of radiation directly to the cancer cells. Not all pheos take up MIBG, so a test is done first to check for this before treatment begins.
Azedra (iobenguane 131) is an MIBG therapy and is the only FDA approved treatment for metastatic pheo para. This treatment requires a 3-4 day hospital stay and sterilization precautions to limit radiation exposure of those in contact with you. Side effects can include nausea, myelosuppression (fewer white/red blood cells and platelets measured in blood) and fatigue.
PRRT (Peptide Receptor Radionuclide Therapy) is a therapy that when injected into the patient’s bloodstream travels to and binds to the tumor delivering a targeted high dose of radiation directly to the cancer cells. A Gallium DOTATE or NETSPOT PET/CT scan is done first to check if the tumor will respond to PRRT.
Lutathera (lutetium Lu 177 dotatate) is used off-label to treat pheo para. Lutathera does not usually require a hospital stay and minimal sterilization precautions are required to limit radiation exposure of those in contact with you.
Some clinical trials are available at the University of Iowa, the NIH, and Cincinnati Children’s Hospital for PRRT. More information can be found at clinicaltrials.gov or by reaching out directly to the institution.
Somatostatin Analogs (SSA's)
Somatostatin is a naturally occurring hormone that acts by binding to somatostatin receptor (SSTR), a receptor that is overexpressed in pheo para. SSA’s such as octreotide and lanreotide work by activating SSTR’s, which can slow tumor growth. Studies have produced mixed results on the effectiveness of SSA’s. Octreotide and lanreotide are administered intravenously (by a needle into the body).
Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). Combination chemotherapy is treatment using more than one anticancer drug. The way the chemotherapy is given depends on the type of cancer being treated and whether it is localized, regional, metastatic, or recurrent.
Chemotherapy drugs that may be used can include cyclophosphamide, vincristine, dacarbazine, and temozolomide monotherapy in malignant pheos for SDHB genetic mutations.
Ablation is a treatment to remove or destroy a body part or tissue or its function. Ablation therapies used to help kill cancer cells include:
- Radiofrequency ablation: A procedure that uses radio waves to heat and destroy abnormal cells. The radio waves travel through electrodes (small devices that carry electricity). Radiofrequency ablation may be used to treat cancer and other conditions.
- Cryoablation: A procedure in which tissue is frozen to destroy abnormal cells. Liquid nitrogen or liquid carbon dioxide is used to freeze the tissue.
Embolization therapy is a treatment to block the artery leading to the adrenal gland. Blocking the flow of blood to the adrenal glands helps kill cancer cells growing there.
Tyrosine kinase inhibitor therapy
Tyrosine kinase inhibitor therapy
TKI is a targeted therapy treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells.
Sunitinib and cabozantinib are types of TKI therapy that can be prescribed off-label and are currently being studied in clinical trials.
New types of treatment are being tested in clinical trials:
Participation in clinical trials for those with progressive disease is critical to finding better treatments for pheo para. It is important to note that placebos are rarely used in cancer treatment clinical trials. For pheo para, they may be used in a clinical trial that compares standard treatment plus a placebo, with standard treatment plus a new treatment. So, everyone participating in a clinical trial will receive, at least, the standard treatment commonly used for pheo para.
In 15%-25% of the cases of pheochromocytoma, the disease is cancerous and has spread to other organs.
The prognosis for these patients is highly variable and can be based on the location of the tumors, genetic status, among other factors. It is highly encouraged for metastatic patients to receive treatment from an experienced, multi-disciplinary pheo para team. There are currently no cures for cancerous pheochromocytoma. However, existing treatment options may reduce the tumors and prolong survival.
why and how
Approximately 35% of pheo paras are hereditary.
Recent research has indicated that people who know they have a genetic mutation, have less metastatic disease, lower likelihood of complications and better overall health outcomes. Regular annual biochemical screening can catch tumors before they are symptomatic.
All patients diagnosed with a pheo par should talk to their doctor about genetic testing. Testing for genetic mutations simply involves a blood test and sending the sample to a lab. Currently, there are approximately 20 genetic mutations identified that can be attributed to a greater risk of developing pheo para, and geneticists believe more genes will be discovered in the near future. It is important to get genetic testing to identify current genetic mutations associated with pheo para as well as yet to be discovered mutations.
If you have a pheo para genetic mutation, your children have a 50/50 chance of inheriting the genetic mutation, although there are two exceptions. (Please see below for more information).
Here is a list of genetic mutations commonly associated with pheo para. Some of these mutations are explained below, other mutations still need to be researched.
NF1, VHL, RE, SDHD, SDHC, SDHB, SDHAF2, TMEM127, SDHA, PHD2, MAX, HIF2A, HRAS, FH, PHD1, MDH2, ATRX, CSDE1 UBTF-MAML3, FOT2, IRP1, DNMT3A, DLST & Chromatin remodeling genes.
To find a genetic counselor near you go to findageneticcounselor.com.
The NIH has an excellent online source of information on Hereditary Pheochromocytoma and Paraganglioma: Your Guide to Understanding Genetic Conditions: Hereditary paraganglioma-pheochromocytoma.
This podcast about PPGL and SDHx mutations, by the Life Raft Group, is very informative, as well.
The following inherited syndromes or gene changes increase the risk of pheochromocytoma:
Multiple endocrine neoplasia 2 syndrome, types A and B (MEN2A and MEN2B)
Multiple endocrine neoplasia, type II (MEN II) is a disorder resulting in tumors in more than one part of the body’s hormone-producing (endocrine) system. The locations of other tumors associated with MEN II include the thyroid, parathyroid, lips, tongue and gastrointestinal tract.
Multiple Endocrine Neoplasia, Type 2 (MEN2) is an inherited condition that is caused by genetic mutations in the RET gene on chromosome 10. When normal, these genes signal when to turn on cell growth and division. A mutation in RET causes the cell growth and division signal to always be on, which increases the risk for specific types of tumors.
MEN2 is classified into three subtypes: MEN2A and MEN2B. All subtypes involve high risk for development of medullary carcinoma of the thyroid and an increased risk for pheochromocytoma; MEN2A has an increased risk for parathyroid adenoma or hyperplasia (excessive growth). Additional features in MEN2B include bumps (neuromas) of the lips and tongue; enlarged lips; and ganglioneuromas (a specific type of polyp within the gastrointestinal tract). In addition, patients with MEN2B tend to be slender with long limbs. About 5% of MEN2A patients and 50% of MEN2B patients have the disease because of a de novo (new) mutation that was not inherited from their parents. If an individual has a RET mutation, then each of his or her children will have a 50% chance of having MEN2, as well. Visit the AMEND support group for more information on MEN2 and the RET gene.
von Hippel-Lindau (VHL) syndrome
Von Hippel-Lindau disease can result in tumors at multiple sites, including the central nervous system, endocrine system, pancreas and kidneys.
VHL is an inherited condition caused by genetic mutations in the VHL gene on chromosome 3. When normal, this gene helps stop tumors from developing. A mutation in the VHL gene increases the risk for many types of benign and cancerous tumors in the brain, spinal cord, eye, ear, kidneys, adrenal glands, and other parts of the body. If an individual has a VHL mutation, each of his or her children will have a 50% chance of having VHL as well. Over 90% of patients with this genetic mutation will develop disease by the age of 65. Approximately 20% of VHL patients will develop pheochromocytoma. Some mutations in the VHL gene primarily increase the risk for developing Pheo. The severity of symptoms varies widely between individuals. Visit the NIH online for more information on VHL.
Neurofibromatosis type 1 (NF1)
Neurofibromatosis 1 (NF1) results in multiple tumors in the skin nerves or deeper nerves in the body (neurofibromas), pigmented skin spots and tumors of the optic nerve.
NF1 is an inherited condition caused by genetic mutations in the NF1 gene on chromosome 17. When normal, these genes help stop tumors from developing. A mutation in NF1 increases the risk for multiple café au lait spots; axillary and inguinal freckling; multiple cutaneous (skin) neurofibromas; and iris Lisch nodules. Learning disabilities are present in at least 50% of individuals with NF1. Less common but potentially more serious manifestations include plexiform neurofibromas; optic nerve and other central nervous system gliomas; malignant peripheral nerve sheath tumors; scoliosis; tibial dysplasia; and vasculopathy.
If an individual has an NF1 mutation, each of his or her children will have a 50% chance of having NF1 as well. Visit the NIH online for more information on NF1.
Hereditary Pheochromocytoma Syndrome is an inherited disorder that result in pheochromocytoma and can be associated with tumors in the kidney and GI tract as well.
Mutations in the Succinate Dehydrogenase Subunit Genes (SDH) increase risk of developing pheochromocytoma. These genes have a role in the energy cycle in our cells and typically act to prevent tumors from forming but when mutated, can lead to tumor formation. Patients with mutations in any of the SDH genes are at increased risk for pheochromocytoma and also increased risk of cancerous tumors in the kidney and GI tract.
This podcast about PPGL and SDHx mutations, by the Life Raft Group, is very informative.
Watch this video about genetics presented at the 2019 Pheo Para Conference.
Pregnancy + Pheo
what you need to know.
Having a pheochromocytoma tumor during pregnancy can be dangerous for the mother-to-be and the baby. Uncontrolled high blood pressure can damage the kidneys, restrict oxygen to the baby and/or cause premature labor. During the stress of labor, a pheo can release massive amounts of catecholamines that may cause hypertensive crisis in the mother and/or complicate the delivery. Therefore, patients with a suspected pheochromocytoma should be monitored closely during pregnancy and have their blood pressure controlled with medication and ideally managed in centers which have experience with the diagnosis and treatment of pheo in pregnancy. Consultation with a pheochromocytoma expert is essential for the best possible outcome.
If you or your partner have a genetic form of pheo para, your child will have a 50/50 chance of inheriting the genetic mutation.
If you or your partner have one of the genetic mutations associated with pheo para, pre-implantation genetic diagnostic (PGD) testing can be used with In Vitro Fertilization (IVF). PGD tests the embryos prior to implantation to only implant embryos that do not have the genetic change seen in you or your partner.
If a woman is already pregnant, and prenatal genetic testing is desired, consultation with a prenatal genetic counselor (findageneticcounselor.com) is recommended. There are genetic testing options using chorionic villus sampling (CVS) and/or amniocentesis at various points in the pregnancy that can be performed, and a full consultation should occur with a specialist.
Source: National Cancer Institute: https://www.cancer.gov/types/pheochromocytoma