Paragangliomas

Many insurance companies will cover genetic testing for paragangliomas. Some of these companies require their patients to see a genetic counselor before they will cover the test. It is important to check your policy and have your provider pre-authorize the test before ordering it. Genetic counselors can help you navigate the insurance implications of testing. You can find a genetic counselor near you here.

Thanks to the Genetic Information Nondiscrimination Act (GINA), health insurance companies cannot change a person’s policy based on their genetic test results. This law does not apply to life insurance, long term care insurance, disability insurance, or military health insurance.

The genes that cause paragangliomas are not completely penetrant. A person could have a mutation in one of these genes and never develop a paraganglioma. The gene mutations do not guarantee that a paraganglioma will occur. Instead they increase the chance that this could happen. The population risk for paragangliomas is much less than 1%. Someone with a gene change has up to a 58% chance of developing them.

Sometimes people who have large paragangliomas in the head or neck region can have hearing loss. The hearing loss is a result of a paraganglioma wrapping around the auditory nerves.

Paragangliomas often occur in the head and neck region because they wrap around the nerves. Because of this paragangliomas often press on the wind pipe. This pressure can make breathing difficult. If this occurs, the paragangliomas will often be removed.

If a person has a personal history of paragangliomas or a family history of paragangliomas, they should consider pursuing genetic counseling and testing. If genetic testing is performed and comes back positive for a change in a gene that causes paragangliomas, all first degree relatives (parents, siblings, and children) should be tested for that same gene change. It would also be wise to inform extended family members (Aunts, Uncles, Cousins, Grandparents, etc.) of the genetic condition. Genetic counseling is strongly urged to help families understand the implications of genetic testing, to coordinate testing of at-risk individuals, and to help families work through the psychosocial issues that may arise before, during, and after the testing process. You can find a genetic counselor near you here.

Cancer centers are the primary treatment center for individuals with a paragangliomas, even if their tumor is not cancerous. However monitoring and management involves doctors from many different specialties including endocrinologists, endocrine surgeons, medical oncologists,radiation oncologists, gastroenterologists, dietitians, and genetic counselors or geneticists. There are also a few national centers of excellent who focus specifically on the care of individuals with paragangliomas such the Paraganglioma & Pheochromocytoma Clinic at the Cleveland Clinic.

Kids who have paraganglioma symptoms can have genetic testing at any age. Children who have a parent with a genetic predisposition to paragangliomas should be tested around age 6 as screening starts at this age. Consultation with a medical geneticist or genetic counselor is recommended before genetic testing so that all of the options and possible test results can be discussed ahead of time. This individual will also help explain the test results and coordinate any follow-up as needed. Visit the National Society of Genetic Counselors website to learn more about genetic counseling services and to find a genetic counselor in a specific location here.

Paragangliomas are benign tumors. If they are not causing any problems, then there is no need for treatment. However, if a paraganglioma is identified that is causing a medical issue (difficulty breathing, hearing loss, etc) or producing hormones treatment is required. First line therapy often either surgery, medical therapy to block the effects of adrenaline excess, and/or radiation therapy. In some cases, surgery is not possible (unresectable) and in July 2018, the FDA approved use of a high-specific-activity radiotherapeutic agent called iobenguane I 131 (Azedra®), for patients with unresectable paraganglioma. The goal of the treatment is to reduce the impact of the paraganglioma and its side effects like hypertension.

There are many great support groups for individuals who have paragangliomas such as Know Pheo Para, Pheo Para Alliance, and facebook groups.

Tumors are either classifed as benign (noncancerous) or malignant (cancerous). Benign tumors are groups of cells that create a mass, but do not spread or invade other tissues of the body. Malignant tumors, however, do spread to other parts of the body. Malignant tumors are much more concerning than benign tumors.

Paragangliomas are most often benign or noncancerous tumors

All cancers and tumors are essentially caused by genetic changes. Some people have genetic changes that cause paragangliomas from conception. These are genetic paragangliomas. Whereas other people have these genetic changes as a result of their environment. These are sporadic paragangliomas.

Pheochromocytomas are paragangliomas (benign tumors) that are in the adrenal glands. The adrenal glands sit on top of the kidneys. Pheochromocytomas are often seen alongside paragangliomas because they essentially are paragangliomas.

Paragangliomas are noncancerous tumors of the peripheral nervous system (the nerves that are not part of the brain and spinal cord). They can occur in any nerve and often near a major artery. The most common site paragangliomas develop is in the abdomen where approximately 85-90% are located. Sometimes paragangliomas release hormones like noradrenaline or adrenaline that cause a high blood pressure, hot flashes, racing heartbeat, and headaches, other times they do not. Most of the time paragangliomas occur as sporadic tumors, that is, they are not inherited. Paragangliomas may also be surgically removed if they are secreting hormones, causing a health problem such making it difficult to breathe, or have become cancerous. Paragangliomas can occur as a isolated finding or part of a genetic conditions such as multiple endocrine neoplasia (MEN) type 2, von Hippel-Lindau syndrome, or Neurofibromatosis type 1.

Several genes and genetic conditions have been connected to paragangliomas.

Most frequently, paragangliomas are found incidentally during an imaging scan and do not cause symptoms. However, sometimes paragangliomas can feel like a bump under the skin.

Paragangliomas can also be called PGLs. Less commonly they may be referred to as a chemodectoma. When paragangliomas are caused by an identified genetic condition, it is common to refer to the situation by the gene name or genetic condition. For example, Familial paraganglioma syndome (FPGL) or SDHD related paragangliomas. They may also be called pheochromocytomas; however, paragangliomas that arise in the adrenal medulla are defined as pheochromocytomas, and those outside the adrenal gland are called paragangliomas.

Paragangliomas can occur as a isolated finding or part of a genetic conditions such as multiple endocrine neoplasia (MEN) type 2, von Hippel-Lindau syndrome, Neurofibromatosis type 1, or Familial Paraganglioma Syndrome.

Paragangliomas can be identified in the body through Magnetic Resonance Imaging (MRI) or other imaging. Anyone with paragangliomas or a family history of paragangliomas should consider pursuing genetic testing. There are several genes associated with paragangliomas as well as various laboratories that can test for them. Genetic counseling is strongly urged to help families understand the implications of genetic testing, to coordinate testing of at-risk individuals, and to help families work through the psychosocial issues that may arise before, during, and after the testing process. You can find a genetic counselor near you here.

Most frequently, paragangliomas are found incidentally during an imaging scan and do not initially cause symptoms. Individuals with large paragangliomas who do have symptoms, may experience hearing loss, difficulty breathing, trouble swallowing, or coughing, depending on the location of the tumor. For example, individuals with paragangliomas in the bladder may have high blood pressure spells with urination or intercourse and blood in the urine (hematuria). If paragangliomas produce hormones like epinephrine (adrenaline), norepinephrine, and dopamine they can cause high blood pressure, rapid heart rate, heart palpitations, arrhythmia, hot flashes, sweating, anxiety, nausea, vomiting or headaches. Uncontrolled levels of these hormones in the body cause serious health problems including stroke, heart attack, and even death.

Paragangliomas may also occur simultaneously with pheochromocytomas and may occasionally occur as multiple tumors.

After a diagnosis or paragangliomas or a paraganglioma genetic predisoposition, the first step is to work closely with a doctor to develop a monitoring and treatment plan. Often the next step will be to obtain a baseline Magnetic Resonance Imaging (MRI) of the head, neck, and abdomen and blood testing to determine if the paraganglioma is producing hormones. Typically, if the paraganglioma does not need to be removed immediately, every other year a full body MRI will be performed to watch its growth. Sometimes endoscopy is done if the person has stomach symptoms. If a paraganglioma is identified that is causing medical issues (difficulty breathing, hearing loss, etc) it will either be surgically removed or minimized with radiation therapy. If there are no symptoms and there is a low risk to develop cancer, a watchful waiting approach may be done.

As of September 15, 2019 there are 23 research studies recruiting individuals who have been diagnosed with a paraganglioma (18 in the United States). Some of these studies are centered on trying new drug therapies, while others are on genetic predisposition and the nature of the condition. To learn more about these research studies click here.

Paragangliomas are tumors, but most of the time they are benign or noncancerous. However, sometimes they can start out as noncancerous and then become cancerous. For this reason, it is important to monitor paraganglioma growth and change.

About 1 person per 100,000 will be diagnosed with paraganglioma per year. It is more commonly seen in individuals who are between 30-40 years old.

The whole body is made of cells and inside of the cells is DNA. The DNA acts as the instructions for the body. Specific pieces of DNA are called genes and every gene has a job it does for the body. Genes are built by nucleic acids that act as a code. The code has to be spelled correctly for the gene to do its job. There are specific genes that prevent paragangliomas from developing.
Genetic testing looks at the DNA through a blood, saliva, or tissue sample. The test does a spell check on the code. If the code is spelled incorrectly, the person with have an increased risk to develop paragangliomas.

Consultation with a medical geneticist or genetic counselor is recommended before genetic testing so that all of the options and possible test results can be discussed ahead of time. This individual will also help explain the test results and coordinate any follow-up as needed. Visit the National Society of Genetic Counselors website to learn more about genetic counseling services and to find a genetic counselor in a specific location here.

Genetic testing is available through several different methods to identify changes or mutations in genes related to the development of a paraganglioma.

If there is a known gene mutation in a family, targeted testing, also known as single site testing, can be ordered. With targeted testing, the laboratory will only look for one specific genetic change instead of scanning the entire gene. This is generally the least expensive option offered by testing companies. In order to have targeted testing, the doctor must provide a copy of a relative’s positive genetic test result so the laboratory knows what genetic change to test.

There are also genetic testing options when a gene mutation has not been identified in the individual living with a paraganglioma. As there are numerous genes that can be associated with paragangliomas, testing for multiple genes may be more efficient and/or cost-effective. This type of testing is often referred to as multi-gene testing or panel testing.

Consultation with a medical geneticist or genetic counselor is recommended before genetic testing so that all of the options and possible test results can be discussed ahead of time. This individual will also help explain the test results and coordinate any follow-up as needed. Visit the National Society of Genetic Counselors website to learn more about genetic counseling services and to find a genetic counselor in a specific location here.

Although paragangliomas are rare, there are many people who are affected by them. You can meet others through support groups, foundations, and functions. A start might be to talk to a doctor about any local families interested in talking or reaching out to the support groups. Some options include: such as Know Pheo Para, Pheo Para Alliance, and facebook groups.

If an individual has paraganglioma and are interested in being a part of a clinical research trial, it is important that they talk to their doctor and family or friends to determine if it’s right for them. Clinicaltrials.gov has a current list of research studies that are recruiting participants. On the homepage of the Clinicaltrials.gov website, search paragangliomas. A list of studies should appear. Those can be narrowed down to focus on studies currently recruiting participants. For more information about individual studies, you or your doctor can usually contact the research team listed on a particular studies page.

Cancer centers are the primary treatment center for individuals with a paragangliomas, even if their tumor is not cancerous. However monitoring and management involves doctors from many different specialties including endocrinologists, endocrine surgeons, medical oncologists,radiation oncologists, gastroenterologists, dietitians, and genetic counselors or geneticists. There are also a few national centers of excellent who focus specifically on the care of individuals with paragangliomas such the Paraganglioma & Pheochromocytoma Clinic at the Cleveland Clinic.

Most cases of sporadic paraganglioma occur in people with no history of the disorder in their family. Other paragangliomas that run in families or are genetic can be inherited in an autosomal dominant inheritance pattern. Genes are passed on from parents to their children in the egg and sperm. The typical person has two of each gene – one they inherited from their mother and one they inherited from their father. Autosomal dominant inheritance indicates that only one of the genes needs to have a mutation for a person to have the disease. If a parent has a mutation in one of these genes there is a 50% chance they will pass it on to their child.

Paragangliomas that occur as part of genetic conditions such as multiple endocrine neoplasia (MEN) type 2, von Hippel-Lindau syndrome, or Neurofibromatosis type 1 run through families in an autosomal dominant pattern. Interestingly paragangliomas related to SDHD gene mutations can appear to skip generations. This is because the paragangliomas associated with the SDHD gene only occur when a person inherits their SDHD mutation from their dad. If they inherit the mutation from their mother they will be a carrier, but not have manifestations. This is due to a mechanism called genomic imprinting.

Most paragangliomas occur sporadically, that is, they are not inherited, but they still will typically have genetic changes within the tumor. In cancerous paragangliomas, genetic testing of the tumor can guide treatment recommendations and identify drug therapies that may be effective against their tumor. For example, a drug designed to counteract RET and HIF1α genes may be helpful in those with tumors with mutations in those genes.

For individuals with a paraganglioma as part of a genetic syndrome or condition, genetic testing can help determine who else in a family might be at increased risk to have the condition and may benefit from genetic counseling and testing.

For individuals who are unsure if their paraganglioma is part of a inherited genetic condition or sporadic should consult a medical professional. A genetic counselor can be found in a specific area using the "Find a Genetic counselor" website .

Paragangliomas often occur in the head and neck region because they wrap around the nerves. Because of this paragangliomas often press on the esophagus. This pressure can make eating and swallowing difficult. If this occurs, the paragangliomas will often be removed.

Some paragangliomas produce hormones like epinephrine (adrenaline), norepinephrine, and dopamine . These hormones can cause high blood pressure, rapid heart rate, heart palpitations, arrhythmia, hot flashes, sweating, anxiety, nausea, vomiting or headaches. Uncontrolled levels of these hormones in the body cause serious health problems including stroke, heart attack, and even death.

Paragangliomas often occur in the head and neck region because they wrap around the nerves. Because of this paragangliomas often press on the wind pipe. This pressure can lead to coughing or difficulty breathing. If this occurs, the paragangliomas will often be removed.

Paragangliomas affect men and women equally. Gender does not define risk of developing a paraganglioma.

Genetic counselors, oncologists, and surgeons all have different roles when treating paragangliomas. Consultation with a medical geneticist or genetic counselor is recommended before genetic testing so that all of the options and possible test results can be discussed ahead of time. This individual will also help explain the test results and coordinate any follow-up as needed. Visit the National Society of Genetic Counselors website to learn more about genetic counseling services and to find a genetic counselor in a specific location here.

When paragangliomas become cancerous there is a 50-69% five year survival rate. Individuals with an SDHB gene have a 34-97% chance that their paragangliomas will become malignant. Individuals with other genetic predisopositions to paragangliomas have less than 6% chance that they will become malignant.

Women who have a treated or managed paraganglioma prior to pregnancy can and do have normal pregnancies and children. Typically, a paraganglioma would be removed surgically prior to pregnancy.

Having a paraganglioma identified while being pregnant involves a different approach. In general, at less than 6 months of pregnancy, surgery (laparoscopic or open) is performed as needed if the paraganglioma is producing adrenaline or other hormones that are negatively impacting the mother or baby. After 6 months of pregnanacy, pharmacologic blockade medications are started if the paraganglioma is producing adrenaline or other hormones.. Most physicians advise delivering the baby via C-section and either removing the paraganglioma at the same time or 4 to 6 weeks later. Obstetricians who specialize in high-risk pregnancies are a critical part of the management team. Consultation with a medical geneticist or genetic counselor may also be recommended so that all of the testing options and possible test results can be discussed ahead of time. This individual will also help explain the test results and coordinate any follow-up as needed. Visit the National Society of Genetic Counselors website to learn more about genetic counseling services and to find a genetic counselor in a specific location here.

It has been indicated that changes in pressure can increase paraganglioma symptoms. If you have paragangliomas it would be wise to avoid scuba diving, flying in noncommercial airplanes, and spending time at high altitudes.

Paragangliomas and conditions associated with paragangliomas are not on the newborn screen in 2019. If a child is exhibiting symptoms of a paraganglioma or there is a family history of paragangliomas, genetic testing would be available through a cancer genetics clinic or a pediatric genetics clinic. Genetic counseling is strongly urged to help families understand the implications of genetic testing, to coordinate testing of at-risk individuals, and to help families work through the psychosocial issues that may arise before, during, and after the testing process.You can find a genetic counselor near you here.