Phaeochromocytoma

Phaeochromocytoma is a rare tumor that develops in the adrenal glands and causes the body to produce too much adrenaline, leading to high blood pressure, headaches, and other serious symptoms that can be life-threatening if not treated.

Table of contents

• What is phaeochromocytoma?
• Where phaeochromocytoma develops
• How common is phaeochromocytoma
• Signs and symptoms
• Causes and risk factors
• How doctors diagnose phaeochromocytoma
• Treatment options
• Outlook and recovery

What is phaeochromocytoma?

A phaeochromocytoma is a rare tumor that grows in the adrenal glands, specifically in the central part called the adrenal medulla (the inner portion of the adrenal gland).^[1] The tumor is made of special cells called chromaffin cells, which normally produce hormones that help the body respond to stress.^[2]

These tumors cause problems because they produce too much of certain hormones called catecholamines, which include adrenaline and noradrenaline (also called epinephrine and norepinephrine).^[3] When released into the blood, these hormones can cause dangerous changes in blood pressure and heart rate, creating symptoms that can range from uncomfortable to life-threatening.^[1]

Most phaeochromocytomas are benign, meaning they are not cancerous. However, approximately 10% to 15% can be malignant, which means the tumor is cancerous and can spread to other parts of the body.^[2] Usually, phaeochromocytoma affects only one adrenal gland, but it can occasionally affect both glands or appear as multiple tumors in one gland.^[8]

Where phaeochromocytoma develops

• Adrenal glands
• Adrenal medulla
• Kidneys (adrenal glands sit on top)

You have two adrenal glands, one sitting on top of each kidney in the back of your upper abdomen. Each adrenal gland has two parts: an outer layer called the adrenal cortex and a central part called the adrenal medulla.^[2]

The adrenal medulla produces catecholamines that help control important body functions such as heart rate, blood pressure, blood sugar levels, and how your body responds to stress. This is often called the “fight or flight” response.^[8] Phaeochromocytomas develop specifically in this central region of the adrenal gland, where these powerful hormones are normally made.^[1]

About 85% of these tumors are located within the adrenal glands, while 15% develop outside the adrenal glands in related nerve tissue. When tumors grow outside the adrenal glands, they are called paragangliomas.^[9]

How common is phaeochromocytoma

Phaeochromocytoma is a rare condition. It is estimated to affect approximately 2 to 8 out of every one million people each year.^[2] The true number of cases may be unknown since many people with phaeochromocytomas do not have symptoms and go undiagnosed.^[2]

Among people who have high blood pressure, less than 1% have a phaeochromocytoma.^[2] The condition can affect anyone at any age, but it most commonly occurs in people between 30 and 50 years of age.^[6] Approximately 10% of cases occur in children, who usually develop symptoms between the ages of 6 and 14.^[10] The condition affects men and women in equal numbers.^[6]

Signs and symptoms

The symptoms of phaeochromocytoma result from the tumor releasing too much adrenaline and noradrenaline into the bloodstream.^[1] However, some phaeochromocytoma tumors do not make extra hormones and cause no symptoms at all.^[2]

When symptoms do occur, they often happen in brief episodes called spells that typically last 15 to 20 minutes. These spells can happen several times a day or less often, and blood pressure may return to normal between episodes, which can make diagnosis difficult.^[1]

The most common symptoms include:

• High blood pressure, which is the most common symptom^[2]
• Severe headaches that can feel like the head is pounding or about to explode^[6]
• Excessive sweating without any clear reason^[2]
• Rapid, forceful, or irregular heartbeat (palpitations)^[6]
• Tremors or feeling shaky^[1]
• Pale skin, especially in the face^[6]
• Shortness of breath^[6]
• Feelings of panic or anxiety^[1]

Less common symptoms may include:

• Pain in the chest or abdomen^[2]
• Nausea and vomiting^[10]
• Constipation^[6]
• Unintentional weight loss^[6]
• Weakness^[2]
• Dizziness^[10]

These symptom episodes can occur spontaneously or may be triggered by certain activities or situations, such as physical exertion, anxiety or stress, changes in body position, bowel movements, certain foods (especially those high in tyramine, a substance found in fermented, aged, or pickled foods), caffeine, certain medications, or medical procedures like surgery and anesthesia.^[6]

If left untreated, a phaeochromocytoma can cause serious or life-threatening damage to other body systems, especially the cardiovascular system. Complications can include stroke, heart attack, heart rhythm problems, heart failure, and other dangerous conditions.^[6]

Causes and risk factors

In most cases, both genetic and environmental factors play a role in the development of phaeochromocytoma.^[10] More than half of phaeochromocytomas arise sporadically, meaning they are not linked to an inherited disorder and their cause is unknown.^[3]

However, approximately 30% to 40% of phaeochromocytomas are hereditary and linked to inherited genetic conditions or genetic mutations that can be passed on to children.^[6] About 30% of these tumors occur as part of familial syndromes.^[9]

People who have a family history of phaeochromocytoma or paraganglioma may be at increased risk. Certain inherited disorders are also associated with increased risk for the condition, including:

• Multiple endocrine neoplasia type 2 (MEN2)^[3]
• Von Hippel-Lindau (VHL) disease^[3]
• Neurofibromatosis type 1 (NF1)^[3]
• Tuberous sclerosis^[10]
• Sturge-Weber syndrome^[10]

There are now 10 genes that have been identified as sites of mutations leading to these tumors. These different genes produce phaeochromocytomas with different ages of onset, secretory profiles, locations, and potential for malignancy.^[9] If you are diagnosed with phaeochromocytoma, it is recommended to talk to your doctor about genetic testing.^[6]

How doctors diagnose phaeochromocytoma

To diagnose phaeochromocytoma, doctors use a combination of laboratory tests and imaging studies.^[11]

Laboratory tests measure the levels of adrenaline and noradrenaline hormones, as well as substances called metanephrines that come from these hormones. Elevated levels of metanephrines are more common when a person has a phaeochromocytoma.^[11]

The main laboratory tests include:

• 24-hour urine test: You collect a urine sample every time you urinate over 24 hours. Your doctor will provide written directions about how to store, label, and return the samples.^[11]
• Blood test: A healthcare professional takes a sample of blood to be tested in the laboratory.^[11]

Before these tests, your healthcare professional may ask you to prepare in specific ways, such as fasting (not eating for a certain amount of time) or temporarily stopping certain medications. Do not skip a medicine dose unless a member of your healthcare team tells you to and gives you directions.^[11]

Imaging tests are needed if the laboratory test results find signs of a phaeochromocytoma. These tests help locate the tumor. Your healthcare professional may order one or more of these imaging tests:^[11]

• CT scan (computed tomography): This combines a series of X-ray images taken from different angles around your body.^[11]
• MRI (magnetic resonance imaging): This uses radio waves and a magnetic field to make detailed images.^[11]
• MIBG imaging (M-iodobenzylguanidine imaging): This is a scan that can detect tiny amounts of an injected radioactive compound that is taken up by phaeochromocytomas.^[11]
• PET scan (positron emission tomography): This scan can also detect radioactive compounds taken up by the tumor.^[11]

Genetic counseling is an important part of the treatment plan for patients with phaeochromocytoma or paraganglioma, especially since many cases have a hereditary component.^[8]

Treatment options

Surgery to remove the tumor is the main treatment for phaeochromocytoma and often returns blood pressure to a healthy range.^[1] Surgical removal is the treatment of choice for the condition and usually results in cure of the hypertension.^[6]

Preoperative preparation is critical for safe surgery. Before removing the tumor, your doctor may prescribe medications to control high blood pressure. This typically involves starting medication called alpha blockers 10 to 14 days before surgery to allow for expansion of blood volume. Patients are encouraged to increase their salt intake and drink plenty of fluids.^[15] After adequate alpha blockade is achieved (usually after 2 days), a beta blocker may be added. If beta blockade is started prematurely, unopposed alpha stimulation could precipitate a dangerous rise in blood pressure.^[15]

The last doses of oral alpha and beta blockers are typically administered on the morning of surgery.^[15] Careful preoperative management is required to control blood pressure, correct fluid volume, and prevent dangerous blood pressure changes during the operation.^[15]

Surgical approaches include laparoscopic (minimally invasive) surgery, which is commonly used for phaeochromocytomas.^[15] The specific surgical approach depends on the tumor’s size, location, and whether it affects one or both adrenal glands.

After surgery, doctors test plasma free metanephrines 2 weeks later to confirm that the tumor has been completely removed. If results are within the reference range, the patient is considered cured.^[15]

Treatment for malignant phaeochromocytoma may include radiation therapy, chemotherapy, and targeted therapy in addition to surgery.^[5] Targeted therapy uses drugs or other substances that attack specific cancer cells with less harm to normal cells.^[5]

Once diagnosed, it is recommended to be seen by a multi-disciplinary medical team with experience treating phaeochromocytoma and paraganglioma.^[6] Continuous medical follow-up may be required to monitor for the development of future tumors.^[10]

Outlook and recovery

If a phaeochromocytoma is detected early, it can be successfully treated and managed in the vast majority of cases.^[6] When diagnosed appropriately, these tumors are usually effectively and completely cured by surgical removal.^[1]

Surgical treatment usually returns blood pressure to normal and alleviates symptoms.^[6] Most people can expect to return to feeling like themselves once the tumor is removed, allowing them to resume normal activities such as walking, socializing, working, exercising, and spending time with family.^[20]

The outlook depends on several factors, including whether the tumor is benign or malignant, whether it can be completely removed by surgery, and whether it has spread to other parts of the body. Regular follow-up care is important to monitor for any recurrence of the tumor.^[8]

For people with hereditary phaeochromocytoma syndromes, ongoing monitoring and genetic counseling for family members may be recommended.^[8]