Pheochromocytoma is a rare tumor that develops in the adrenal gland, causing the release of excessive amounts of adrenaline and noradrenaline into the bloodstream. Though uncommon, this condition can cause serious complications if left untreated, but early detection and proper management can lead to successful outcomes in the vast majority of cases.

What is Pheochromocytoma?

A pheochromocytoma is a rare tumor that forms in the center of one or both adrenal glands, specifically in a region called the adrenal medulla. The adrenal glands are small, triangle-shaped organs located on top of each kidney. They produce various hormones that help control essential body functions like blood pressure, heart rate, and how the body responds to stress.^[1]

The tumor is made up of special cells called chromaffin cells, which normally produce hormones called catecholamines. These include adrenaline (also known as epinephrine), noradrenaline (norepinephrine), and dopamine. These are the same hormones responsible for the “fight or flight” response your body experiences when facing danger or stress.^[2]

When a pheochromocytoma develops, these cells begin producing too much of these hormones, releasing them into the bloodstream either continuously or in sudden bursts. This excess release is what causes most of the symptoms people experience. The condition typically affects only one adrenal gland, though in some cases both glands may be involved or there may be multiple tumors within a single gland.^[1]

The good news is that most pheochromocytomas are benign, meaning they are not cancerous. However, approximately 10 to 15 percent of cases may be malignant, meaning the tumor is cancerous and has the potential to spread to other parts of the body. Even benign tumors require treatment because the hormones they produce can cause serious and potentially life-threatening complications.^[2]

How Common is Pheochromocytoma?

Pheochromocytoma is considered extremely rare. Studies estimate that it affects no more than 2 to 8 out of every one million people each year. Because the condition is so uncommon and many people with small tumors experience no symptoms at all, the true number of cases may be underestimated. Many individuals with pheochromocytoma go undiagnosed for years.^[2]

The condition can affect anyone at any age, from children to the elderly. However, it occurs most frequently in adults between the ages of 30 and 50. Both men and women are affected equally by pheochromocytoma. Among all cases, approximately 10 percent occur in children, who usually develop symptoms between the ages of 6 and 14.^[6]

Less than 1 percent of people who have high blood pressure actually have a pheochromocytoma as the underlying cause. However, because high blood pressure is such a common problem, doctors need to be aware of this rare possibility, especially when blood pressure is difficult to control with usual medications or when other characteristic symptoms are present.^[2]

Risk Factors and Causes

In many cases, pheochromocytomas develop sporadically, meaning they appear without any clear cause or family history. However, research has revealed that approximately 30 to 40 percent of pheochromocytomas are actually hereditary, meaning they are linked to inherited genetic conditions. This is a much higher percentage than previously thought.^[6]

Several genetic syndromes and inherited disorders are associated with an increased risk of developing pheochromocytoma. These include multiple endocrine neoplasia type 2 (MEN 2), a condition that causes tumors to develop in multiple hormone-producing glands; von Hippel-Lindau disease (VHL), which increases the risk of various types of tumors; and neurofibromatosis type 1 (NF1), a condition that causes tumors to grow along nerves. Other associated conditions include tuberous sclerosis, Sturge-Weber syndrome, and ataxia-telangiectasia.^[3]

Having a family history of pheochromocytoma or paraganglioma (a related type of tumor that forms outside the adrenal glands) increases a person’s risk. Scientists have now identified at least 10 different genes where mutations can lead to these tumors. These different genetic variations produce pheochromocytomas with different characteristics, including different ages of onset, different hormone production patterns, different locations, and varying potential for becoming malignant.^[9]

Signs and Symptoms

The symptoms of pheochromocytoma result from the excessive release of catecholamine hormones into the bloodstream. These symptoms can vary greatly from person to person. Some individuals may experience no symptoms at all, especially if the tumor is small and not producing large amounts of hormones. However, when symptoms do occur, they can be quite dramatic and frightening.^[2]

The most common symptoms of pheochromocytoma form a classic triad: high blood pressure, severe headaches, and excessive sweating. High blood pressure, or hypertension, is by far the most common problem. This elevated blood pressure may be constant, staying high all the time, or it may occur in episodes that come and go. Between these episodes, blood pressure may return to normal, which can make diagnosis more challenging.^[1]

Many people with pheochromocytoma experience what are called “spells” or “attacks.” These episodes typically come on suddenly and can last anywhere from a few minutes to several hours, though most last between 15 and 20 minutes. During these spells, people commonly experience severe, throbbing headaches that feel like the head might explode. The headache is often accompanied by profuse sweating, even when the room is not hot. Heart palpitations are also common, with the heart beating rapidly, forcefully, or irregularly. Many people describe feeling an intense “adrenaline rush” for no apparent reason.^[6]

Other symptoms that may occur during these episodes include tremors or shaking, especially in the hands; paleness of the skin, particularly in the face; shortness of breath; dizziness or lightheadedness; and a sensation of panic or impending doom, similar to a panic attack. Some people experience chest pain or abdominal pain. Less common symptoms include nausea and vomiting, constipation or diarrhea, weakness, and unintentional weight loss despite having a good appetite.^[2]

These spells can occur spontaneously without any obvious trigger, or they may be brought on by specific activities or situations. Common triggers include physical exertion or exercise, anxiety or emotional stress, changes in body position such as bending over or lying down, certain medical procedures including surgery and anesthesia, bowel movements, labor and delivery in pregnant women, and consumption of caffeine. Certain medications can also trigger episodes, including steroids, decongestants, and some psychiatric medications. Foods high in a substance called tyramine, which is found in fermented, aged, pickled, cured, or spoiled foods, can also provoke symptoms.^[6]

Why Pheochromocytoma is Dangerous

Although the tumor itself is usually benign, pheochromocytoma can be extremely dangerous because of the powerful effects of the excess catecholamine hormones it produces. If left untreated, a pheochromocytoma can result in severe or life-threatening damage to other body systems, especially the cardiovascular system including the heart and blood vessels.^[1]

The extremely high blood pressure caused by these tumors can lead to serious complications such as stroke, when blood vessels in the brain are damaged; heart attack, when the heart muscle doesn’t receive enough blood; dangerous heart rhythm problems called arrhythmias; congestive heart failure, when the heart cannot pump blood effectively; and damage to the eyes, kidneys, and other organs. Some patients may develop shock lung or experience dangerously low blood pressure and fainting.^[7]

Unfortunately, pheochromocytomas are sometimes not diagnosed until a patient is admitted to the intensive care unit with one of these devastating complications, a situation sometimes referred to as adrenergic crisis. When doctors look back at the medical history of these patients, they often find that the person had been experiencing symptoms for years or even decades without receiving the correct diagnosis.^[7]

How Pheochromocytoma is Diagnosed

Diagnosing pheochromocytoma typically involves several steps, beginning with a thorough medical history and physical examination. However, because the symptoms can mimic many other conditions, including panic attacks, anxiety disorders, hyperthyroidism, and other causes of high blood pressure, diagnosis can be challenging and is often delayed.^[2]

If a doctor suspects pheochromocytoma, they will order specific laboratory tests to measure the levels of catecholamines and their breakdown products, called metanephrines, in the blood or urine. These tests are the cornerstone of diagnosis. A 24-hour urine test involves collecting all urine produced over a full 24-hour period, which is then tested for elevated levels of metanephrines and catecholamines. Blood tests can also measure these substances. Elevated levels of metanephrines are highly suggestive of pheochromocytoma.^[11]

Before these tests, patients may need to follow certain preparation instructions. This might include fasting for a period of time or temporarily stopping certain medications that could interfere with test results. It is crucial not to stop any medication without explicit instructions from a healthcare provider.^[11]

Once biochemical testing confirms the presence of excess catecholamines, imaging tests are needed to locate the tumor. Several different imaging techniques may be used. A CT scan (computed tomography) combines multiple X-ray images taken from different angles to create detailed cross-sectional pictures of the body. An MRI (magnetic resonance imaging) uses magnetic fields and radio waves to produce detailed images of soft tissues. These tests can usually identify the location and size of the tumor.^[11]

For more challenging cases, specialized nuclear medicine scans may be used. MIBG imaging (metaiodobenzylguanidine) involves injecting a small amount of radioactive material that is specifically taken up by pheochromocytoma cells, making the tumor visible on special scans. PET scans (positron emission tomography) work similarly, using different radioactive compounds to detect tumor tissue.^[11]

Because a significant percentage of pheochromocytomas are associated with inherited genetic conditions, genetic counseling and testing are now considered an important part of the diagnostic process. This testing can identify whether a person has one of the known genetic mutations associated with pheochromocytoma, which has implications for the patient’s long-term care and for family members who might also be at risk.^[8]

Treatment Approaches

The definitive treatment for pheochromocytoma is surgical removal of the tumor. In most cases, surgery can completely cure the condition, with blood pressure returning to normal or near-normal levels after the tumor is removed. However, careful preparation before surgery is absolutely essential to ensure patient safety during and after the procedure.^[1]

Before surgery can be performed, patients typically need several weeks of medical management to control blood pressure and heart rate. This preoperative preparation usually involves medications called alpha blockers, which help relax blood vessels and reduce blood pressure. These medications are typically started 10 to 14 days before surgery to allow time for blood volume to expand. Patients are often encouraged to increase their salt intake during this period.^[15]

After adequate alpha blockade has been established (usually after about two days), beta blockers may be added to control heart rate and prevent irregular heartbeats. It is crucial that beta blockers are not started before alpha blockers, as this could lead to a dangerous rise in blood pressure. Other medications, including calcium channel blockers, may also be used to help control symptoms. The last doses of these medications are typically given on the morning of surgery.^[15]

The surgical procedure itself is most commonly performed using minimally invasive techniques when possible. Laparoscopic adrenalectomy, where the surgeon removes the affected adrenal gland through several small incisions using a camera and specialized instruments, is now the preferred approach for most pheochromocytomas. This technique typically results in less pain, shorter hospital stays, and faster recovery compared to traditional open surgery. However, in some cases, particularly for very large tumors or when cancer is suspected, open surgery may be necessary.^[15]

For patients with malignant pheochromocytoma where the cancer has spread to other parts of the body, treatment becomes more complex. Options may include additional surgery to remove metastatic tumors when possible, radiation therapy to target cancer cells, chemotherapy using drugs that kill rapidly dividing cells, and targeted therapies that attack specific characteristics of cancer cells. Radioactive MIBG therapy, which delivers radiation directly to tumor cells, may also be used in some cases.^[14]

Long-term Outlook and Follow-up

For most people with benign pheochromocytoma, the outlook after successful surgical removal is excellent. Many patients experience complete resolution of their symptoms, particularly if the high blood pressure was solely due to the tumor. Blood pressure often returns to normal, though some patients may still need blood pressure medications, especially if they had pre-existing hypertension before the tumor developed.^[1]

After surgery, follow-up testing is crucial. Blood tests to measure plasma free metanephrines are typically performed about two weeks after surgery to confirm that the tumor was completely removed and hormone levels have returned to normal. If levels remain elevated, this may indicate that tumor tissue remains, either at the original site or elsewhere in the body.^[15]

Long-term monitoring is important because pheochromocytomas can recur, meaning they can come back either in the same location or in a different area. This is particularly true for people with hereditary forms of the disease or those who had bilateral tumors (tumors in both adrenal glands). Patients typically need periodic follow-up appointments with blood or urine tests to check for recurrence. The frequency of these tests depends on individual risk factors, including whether the tumor was hereditary and whether it was malignant.^[14]

For patients with hereditary pheochromocytoma syndromes, lifelong surveillance is necessary not only to watch for recurrent pheochromocytoma but also to screen for other tumors associated with their specific genetic syndrome. Family members of patients with hereditary pheochromocytoma may also benefit from genetic testing and screening.^[8]

How the Body is Affected: Understanding the Disease Process

To understand how pheochromocytoma affects the body, it helps to know how catecholamine hormones normally work. The adrenal medulla produces three main catecholamines: dopamine, norepinephrine, and epinephrine. These hormones help regulate heart rate, blood pressure, blood sugar levels, and the body’s response to stress. They are essential for the “fight or flight” response that prepares the body to react to danger.^[2]

When a pheochromocytoma develops, it disrupts this carefully balanced system. The tumor cells continuously or intermittently produce and release excessive amounts of these powerful hormones. Different tumors may produce different combinations of catecholamines. Some produce mainly epinephrine, while others produce primarily norepinephrine. A few produce dopamine. The specific hormones produced influence which symptoms a patient experiences.^[9]

The excess norepinephrine causes blood vessels throughout the body to constrict or narrow, which dramatically increases blood pressure. This puts tremendous strain on the heart, which must work harder to pump blood through the constricted vessels. Over time, this can damage the heart muscle and lead to heart enlargement and eventual heart failure if left untreated.^[9]

The excess epinephrine increases heart rate and makes the heart beat more forcefully. It also causes blood sugar levels to rise by promoting the breakdown of stored glucose and preventing insulin from working properly. This is why some people with pheochromocytoma develop symptoms similar to diabetes. The increased metabolic rate caused by excess catecholamines explains why some patients experience unintentional weight loss despite eating normally or having a good appetite.^[9]

The sweating, tremors, and pale skin that many patients experience are direct results of catecholamine effects on sweat glands, muscles, and blood vessels in the skin. The anxiety, panic sensations, and feelings of impending doom reflect the psychological effects of having the body in a constant state of “fight or flight” arousal, even when there is no actual danger present.^[6]

Chronic exposure to high levels of catecholamines can damage multiple organ systems. The kidneys may be damaged by prolonged high blood pressure. The heart muscle can develop areas of damage and scarring. Blood vessels throughout the body may develop accelerated atherosclerosis, where fatty deposits build up in artery walls. In severe cases, the strain on the heart can lead to cardiomyopathy, where the heart muscle becomes weakened and enlarged and cannot pump blood effectively.^[7]

Living with Pheochromocytoma Before Treatment

The period between diagnosis and treatment can be challenging for patients with pheochromocytoma. Understanding what triggers symptoms and learning how to minimize these triggers can help improve quality of life during this time. Patients are generally advised to avoid activities and substances known to provoke symptoms, such as strenuous physical activity, stressful situations when possible, certain medications, and foods high in tyramine.^[6]

Working closely with a medical team experienced in treating pheochromocytoma is essential. Blood pressure and heart rate need to be carefully monitored and controlled with medications. Patients need education about warning signs that require immediate medical attention, such as severe headache, chest pain, or extremely high blood pressure readings.^[6]

The psychological impact of living with pheochromocytoma should not be underestimated. The unpredictable nature of symptom spells, combined with the fear and physical sensations they produce, can significantly affect mental health and quality of life. Support from family, friends, and healthcare providers is important. Some patients benefit from connecting with others who have experienced the same condition through patient support organizations.^[6]