Pheochromocytoma in Children

Pheochromocytoma is a rare tumor that develops in the adrenal glands, which sit above the kidneys. The adrenal glands produce hormones that help control important functions such as blood pressure, heart rate and the body's response to stress.

A pheochromocytoma develops from cells that normally produce hormones called catecholamines, including epinephrine (adrenaline) and norepinephrine. When a tumor releases too much of these hormones, it can cause sudden or persistent increases in blood pressure and other symptoms.

Pheochromocytoma is rare in children. When it does occur, it is more likely than adult pheochromocytoma to be associated with an inherited genetic condition or tumors in both adrenal glands.

A similar tumor called a paraganglioma develops outside the adrenal glands. Pheochromocytomas and paragangliomas are often evaluated and treated together because they share many of the same symptoms, genetic causes and treatments.

Symptoms of Pheochromocytoma

Some children with pheochromocytoma have no symptoms, and the tumor may be discovered during testing for another condition. When symptoms occur, they can happen in episodes as the tumor releases bursts of hormones.

Common symptoms include:

• High blood pressure
• Severe or recurring headaches
• Fast heartbeat or pounding heartbeat (palpitations)
• Excessive sweating
• Warmth or flushing
• Trembling or shaking
• Anxiety or a feeling similar to a panic attack
• Chest pain
• Shortness of breath
• Blurred vision
• Nausea, vomiting or abdominal pain
• Constipation or diarrhea
• Muscle weakness
• Unexplained weight loss
• Increased thirst or urination
• Trouble sleeping
• Tingling, burning or numbness in the legs or feet
• Increased sensitivity to heat

Symptoms may be triggered or worsened by physical or emotional stress, exercise, certain medications or other situations that cause the tumor to release catecholamines.

High Blood Pressure in Children

High blood pressure is one of the most important signs of pheochromocytoma. Unlike the gradual blood-pressure changes that occur with many common conditions, pheochromocytoma can cause very high blood pressure or sudden episodes of extremely high blood pressure.

If your child has severe headache, chest pain, difficulty breathing, confusion, vision changes or other concerning symptoms along with very high blood pressure, seek emergency medical care.

What Causes Pheochromocytoma?

Pheochromocytoma occurs when certain adrenal cells grow abnormally and form a tumor. In many children, the tumor is associated with an inherited genetic change.

Conditions associated with pheochromocytoma and paraganglioma include:

• Von Hippel-Lindau disease
• Multiple endocrine neoplasia type 2 (MEN2)
• Neurofibromatosis type 1
• Hereditary paraganglioma syndromes
• Other inherited genetic conditions

Some children develop pheochromocytoma without a known inherited condition.

Because pheochromocytoma can be associated with inherited conditions, genetic counseling and testing are often an important part of a child's evaluation.

Diagnosing Pheochromocytoma

Diagnosing pheochromocytoma usually involves blood or urine testing to determine whether the tumor is producing excessive catecholamines. Your child's doctor may also use imaging tests to locate the tumor and determine whether it has spread.

Blood & Urine Tests

The first step is usually measuring metanephrines, substances produced when the body breaks down catecholamines.

Testing may include:

• Plasma free metanephrines: A blood test that measures metanephrine and normetanephrine levels.
• 24-hour urine metanephrines: Measures the amount of metanephrines produced and passed into the urine over a full day.
• Other blood or urine tests for catecholamines and related hormones when needed.

Certain medications, foods, stress and other factors can affect these test results. Your child's care team will provide instructions about how to prepare for testing.

Clonidine Suppression Test

If initial blood or urine testing does not clearly establish a diagnosis, your child's doctor may recommend a clonidine suppression test.

During this test, your child receives clonidine, a medication that normally reduces the release of norepinephrine. Blood samples are then collected to measure hormone levels.

If norepinephrine or related hormone levels remain elevated despite clonidine, the results may support a diagnosis of pheochromocytoma or a related tumor.

Imaging Tests

Once laboratory testing suggests pheochromocytoma, imaging can help locate the tumor and determine whether there are additional tumors.

Imaging may include:

• MRI: Provides detailed images of the adrenal glands and surrounding tissues without radiation. MRI is often particularly useful for children.
• CT scan: Uses X-rays to create detailed images of the adrenal glands and other parts of the body.
• Ultrasound: Uses sound waves to examine the adrenal glands and surrounding structures.
• MIBG scan: Uses a small amount of a radioactive substance that can be taken up by certain adrenal tumor cells to help locate pheochromocytomas and paragangliomas.
• PET scan: Uses a radioactive tracer to identify certain tumors or areas where the disease may have spread.

Your child's doctor will choose imaging based on your child's symptoms, laboratory results, suspected genetic condition and other factors.

Genetic Testing

Because inherited genetic conditions are common in children with pheochromocytoma, your child's doctor may recommend genetic counseling and testing.

Genetic testing can help identify an inherited condition that may:

• Explain why the tumor developed
• Affect the type and extent of treatment
• Help doctors determine whether other tumors could develop
• Guide long-term monitoring
• Provide information that may be important for other family members

Treating Pheochromocytoma

The primary treatment for a pheochromocytoma that can be removed is surgery. Because the tumor can release large amounts of hormones during surgery, careful preparation is essential.

Preparing for Surgery

Before surgery, your child's care team will usually prescribe medications to control the effects of excess catecholamines.

These medications help lower blood pressure and reduce the risk of dangerous changes in blood pressure or heart rate during surgery.

Your child may receive:

• Alpha-blockers to relax blood vessels and control blood pressure
• Beta-blockers, when needed, to control a rapid heart rate after adequate alpha-blockade
• Increased fluids and salt intake in some cases to help restore blood volume

Your child's blood pressure and heart rate will be closely monitored before, during and after surgery.

Adrenalectomy

An adrenalectomy is surgery to remove an adrenal gland containing a pheochromocytoma.

Depending on the tumor's size, location, number of tumors and other factors, surgeons may use:

• Laparoscopic or minimally invasive surgery, which uses several small incisions and specialized instruments
• Open surgery, which may be recommended for larger or more complex tumors

If both adrenal glands contain tumors, surgeons may consider an approach that preserves part of the adrenal tissue when appropriate. Your child's treatment team will discuss the best surgical approach based on the individual tumor and the child's overall health.

After surgery, your child's blood pressure and hormone levels will be monitored closely.

Treatment for Advanced or Metastatic Pheochromocytoma

Some pheochromocytomas or paragangliomas can spread to other parts of the body. When surgery cannot remove all of the tumor or the disease has spread, treatment may include a combination of approaches.

Depending on the tumor's characteristics, treatment may include:

• Surgery to remove tumors when possible
• Radiation therapy
• Chemotherapy
• Targeted medications
• Radioactive MIBG therapy for tumors that take up MIBG
• Other specialized therapies based on the tumor's genetic and molecular characteristics

Your child's specialists will develop a treatment plan based on whether the tumor is localized or has spread, its location, genetic characteristics and how it responds to treatment.

Follow-Up Care

Children who have had a pheochromocytoma or paraganglioma need long-term follow-up because these tumors can sometimes return or new tumors can develop, particularly in children with inherited genetic conditions.

Follow-up may include:

• Regular blood-pressure checks
• Blood or urine metanephrine testing
• Periodic imaging
• Genetic counseling and testing
• Screening for other tumors associated with an inherited condition

At UVA Health Children's, children with pheochromocytoma benefit from coordinated care among pediatric specialists, including endocrinology, surgery, oncology, genetics and other specialists as needed.