Paraganglioma is a rare type of tumor that develops near major blood vessels and nerves throughout the body, most commonly in the head, neck, and abdomen. While most of these tumors are not cancerous, they can cause serious health problems because many of them produce excess hormones that affect blood pressure, heart rate, and other vital body functions. Understanding this condition is important because early detection and proper treatment can prevent potentially life-threatening complications.
How Common Is Paraganglioma?
Paraganglioma is an extremely rare condition that affects very few people. It is estimated that only about 2 out of every 1 million people develop this tumor each year.[1][3] This rarity means that many doctors may never encounter a case throughout their entire medical career. The condition is most commonly diagnosed in adults between the ages of 30 and 50 years, though it can occur at any age.[1][4] About 10% of cases are found in children.[1] The disease affects men and women equally, and it occurs across all races and ethnic groups.[4]
The tumor can develop in different parts of the body, which affects how common certain types are. Approximately 85% of paragangliomas develop in the abdomen, making this the most frequent location. About 12% occur in the chest, and only around 3% are found in the head and neck region.[4][6] Tumors that develop in the head and neck are typically the ones most likely to cause noticeable symptoms that lead to diagnosis.
What Causes Paraganglioma?
The exact cause of paraganglioma is not always clear, and many cases develop without any obvious reason. Scientists have identified that these tumors form from special cells called chromaffin cells, which are nerve cells that produce and release hormones called catecholamines.[1] These cells are part of the body’s nervous system and are normally found scattered throughout the body near blood vessels and nerve pathways. When these cells begin to grow abnormally, they can form a paraganglioma tumor.
While most paragangliomas occur spontaneously without a known trigger, a significant portion are linked to genetic factors. Research has shown that approximately 30 to 40% of paragangliomas are hereditary, meaning they run in families due to inherited genetic changes.[4][13] In fact, having a family history of this tumor is the only known risk factor for developing the condition.[8][16] There are no known environmental, dietary, or lifestyle factors that have been connected to the development of paraganglioma.
Scientists have discovered mutations in approximately 20 different genes that may lead to the formation of paragangliomas. Some of the most important genes involved include RET, VHL, NF1, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, and MAX.[3] These genetic changes can be part of several inherited conditions that increase the risk of developing paragangliomas.
Groups at Higher Risk
Because most cases of paraganglioma occur randomly without a clear cause, there are very few identifiable risk factors. The strongest risk factor is having a family history of the disease or being part of a family with certain inherited genetic syndromes. Several genetic conditions are associated with an increased likelihood of developing paragangliomas.
Multiple Endocrine Neoplasia Type 2 (MEN2) is caused by mutations in the RET gene and can lead to multiple types of tumors in hormone-producing glands, including paragangliomas.[3] Von Hippel-Lindau syndrome is caused by changes in the VHL gene and is associated with various types of tumors in the brain, eyes, kidneys, pancreas, and paragangliomas. Only about 10 to 20% of people with this syndrome develop these tumors.[8][16]
Neurofibromatosis Type 1 (NF1) is characterized by coffee-colored skin spots and nerve tumors in the skin. Only about 5% of people with this condition will develop paragangliomas.[8][16] Hereditary Paraganglioma Syndrome is caused by mutations in genes related to an enzyme called succinate dehydrogenase (SDH), including SDHB, SDHC, and SDHD mutations. Each of these mutations can cause different forms of the disease.[3][8]
Many of these genetic conditions are passed down through families in a pattern called autosomal dominant inheritance. This means that if a parent has the genetic mutation, each of their children has a 50% chance of inheriting it and potentially developing the disease. Genetic testing should be considered for patients who have tumors in multiple locations, a family history of paragangliomas, signs or symptoms of the genetic syndromes mentioned above, or who were diagnosed at a young age.[8]
Signs and Symptoms
The symptoms of paraganglioma vary greatly depending on where the tumor is located in the body and whether it produces excess hormones. Some people with paraganglioma have no symptoms at all, and their tumor is discovered accidentally during tests for other medical reasons.[4][13] This is particularly common for tumors in the head and neck, which often do not produce hormones.
When symptoms do occur, they can be quite varied. Paragangliomas that form in the head or neck area may cause symptoms related to their physical presence and pressure on nearby structures. These symptoms can include a rhythmic pulsing or whooshing sound in the ears called pulsatile tinnitus, trouble swallowing, a hoarse voice, hearing loss, blurred vision, dizziness, headaches, or vision problems.[2][4] Some people may notice a lump or swelling in their neck where the tumor is located.
When paragangliomas form in other parts of the body, particularly in the abdomen or chest, they are more likely to produce excess amounts of hormones called catecholamines. These hormones include adrenaline (also called epinephrine), norepinephrine (noradrenaline), and dopamine.[1] These hormones normally help control heart rate, blood pressure, blood sugar levels, and how the body responds to stress. When too much of these hormones is released into the bloodstream, it causes a distinct set of symptoms.
The most common symptoms caused by excess hormone production include high blood pressure, which can be persistent or come and go in episodes. Other frequent symptoms include a fast or pounding heartbeat (palpitations), headaches, excessive sweating (especially at night), anxiety, tremors or shaking, and a pale appearance.[3][4][13] Some people also experience nausea, vomiting, abdominal or back pain, unexplained weight loss, and persistent fatigue or exhaustion.
These symptoms can occur as sudden episodes or “spells” that may last anywhere from a few minutes to several hours, though most attacks last less than an hour.[4][13] The spells may happen spontaneously or can be triggered by certain activities or situations. Common triggers include physical activity, changes in body position, pressure on the abdomen, certain foods or drinks, stress, and some medications. The frequency of these episodes varies greatly from person to person, occurring anywhere from several times a day to once every few months.
Preventing Paraganglioma
Because most cases of paraganglioma occur without a known environmental or lifestyle cause, there are no proven prevention strategies that can reduce the risk of developing this tumor. The only identified risk factor is having certain genetic conditions or a family history of the disease, which cannot be changed or prevented.
However, for people who have a family history of paraganglioma or who carry one of the genetic mutations associated with increased risk, regular medical monitoring and screening can help detect tumors early, before they cause serious complications. This is not prevention in the traditional sense, but rather early detection, which can make treatment more successful and potentially life-saving.
If you have been diagnosed with one of the genetic syndromes associated with paragangliomas, or if you have family members who have had these tumors, it is important to discuss genetic testing and regular screening with your healthcare provider. Early detection through blood and urine tests to check hormone levels, along with periodic imaging studies, can identify tumors when they are smaller and easier to treat.
Family members of people diagnosed with hereditary paraganglioma should consider genetic counseling and testing, especially if the patient is found to have a genetic mutation. Children who inherit these genetic changes from a parent may benefit from regular monitoring starting at an appropriate age determined by their healthcare provider. This approach allows for the detection of tumors at an early stage when treatment outcomes are typically better.
How Paragangliomas Affect the Body
Understanding how paragangliomas change the normal functioning of the body helps explain why these tumors can be dangerous even when they are not cancerous. The key to understanding their effects lies in how they interact with the body’s hormonal systems and their physical location near critical structures.
Paragangliomas develop from chromaffin cells, which are specialized nerve cells that produce catecholamines. In normal circumstances, these hormones are carefully regulated by the body and released in appropriate amounts in response to stress or physical demands. The adrenal glands, located on top of each kidney, contain tissue with these same cells and normally produce these hormones in a controlled way. However, paragangliomas form outside the adrenal glands, along blood vessels and nerve pathways throughout the body.[1]
When paraganglioma cells produce excess catecholamines, they release these powerful hormones into the bloodstream without the body’s normal control mechanisms. Adrenaline and norepinephrine cause the heart to beat faster and more forcefully, increase blood pressure by tightening blood vessels, raise blood sugar levels, and prepare the body for “fight or flight” responses. When these hormones are released continuously or in sudden bursts by a tumor, they can cause dangerously high blood pressure, irregular heart rhythms, and put excessive stress on the heart and blood vessels.[1][8]
The physical presence of the tumor itself can also cause problems depending on where it grows. Paragangliomas most commonly develop near the carotid artery in the neck, which is a major blood vessel that supplies blood to the brain. Tumors in this location, called carotid body tumors, can grow and press on nearby structures including nerves that control speaking, swallowing, and facial movement. This explains why some people with head and neck paragangliomas experience voice changes, difficulty swallowing, or other symptoms related to nerve compression.
Not all paragangliomas produce hormones. Some tumors, particularly those in the head and neck region, are described as “biochemically silent,” meaning they don’t release significant amounts of catecholamines.[4][13] These tumors typically cause symptoms only through their physical size and pressure effects on surrounding tissues. Only about 1 to 5% of head and neck paragangliomas produce enough hormones to cause symptoms.[4][5]
Paragangliomas are usually slow-growing tumors, though the growth rate can vary from case to case.[1][4] Most paragangliomas are benign, meaning they do not spread to other parts of the body. However, approximately 20% of paragangliomas are malignant (cancerous).[1] One of the challenges with these tumors is that it can be very difficult, even under a microscope after surgery, to tell the difference between benign and malignant paragangliomas. A tumor is generally considered malignant if it spreads to nearby tissues, spreads to distant parts of the body like the lungs or bones, or comes back after treatment. Studies show that approximately 35 to 50% of malignant paragangliomas may spread to other parts of the body.[1][3]
The location of the paraganglioma influences its likelihood of being malignant. Tumors in the head and neck are less likely to spread compared to tumors in the chest, abdomen, and pelvis.[4] This difference is important when doctors are planning treatment and determining how closely a patient needs to be monitored after treatment.
