von Hippel Lindau Disease

According to the VHL Family Alliance, one in every 32,000 people in the United States is affected by the disease. If one of your parents has von Hippel Lindau disease, you have a 50% chance of inheriting it.

Von Hippel Lindau disease was first described at the beginning of the 20th century by Eugen von Hippel and Arvid Lindau. VHL is an inherited mutation of the von Hippel Lindau gene, which is a protein in the body’s cells. It can affect several different parts of the body and cause several types of problems.

The mutation causes the cells to lose their ability to process information properly, and they act as if they are starved of oxygen. This makes other cells around the affected cells produce abnormally high numbers of blood vessels. Tumors and cysts may then form in those areas of the body.

The eyes, lower part of the brain, spine, pancreas, adrenal glands and kidney are affected most often. While most of these tumors are benign (not cancer), they may grow and cause damage to organs. VHL also can cause malignant (cancer) tumors in the kidney or pancreas.

Patients with VHL may have one or more of several diseases, including the following.

Pheochromocytoma

Your body has two adrenal glands, one on top of each kidney. Each gland has two parts:

• The cortex, or outer part, makes hormones that help maintain blood pressure and salt balance
• The medulla, or inner part, is made up of nerve cells and is a source of catecholamines, hormones that play a part in the body’s response to stress.

A pheochromocytoma is a tumor that starts in the adrenal medulla and causes it to make too many catecholamines, particularly normetanephrine (a breakdown product of norepinephrine). About 10% to 15% of people with VHL II have pheochromocytomas in one or more areas of the body.

Sometimes a catecholamine-producing tumor starts in nerve cells located outside the adrenal glands. These are called paragangliomas. However, they often are referred to as pheochromocytomas.

Although a pheochromocytoma is a tumor, it is rarely malignant (cancer) in von Hippel Lindau disease, meaning it is unlikely to spread to other places in the body. If found early, pheochromocytomas are not difficult to treat. However, if not treated, they may cause dangerously high blood pressure during physical stressors such as accidents, surgery or childbirth.

Hemangioblastomas

Between 60% and 80% of patients with VHL develop hemangioblastomas, a type of benign tumor, in the cerebellum (part of the brain), the spinal cord or the brain stem. The average age for developing hemangioblastomas is 33, but they have been found in patients as young as 9. Although these are benign tumors, they can cause problems in brain or spinal cord function because of their size, number or location in the nervous system.

Kidney Cancer

Kidney cancer affects up to 40% of people with von Hippel Lindau disease and is the most common cause of disease-related death in people with VHL. Kidney cancer can start as a single tumor in one kidney or as multiple tumors in both kidneys. The key to treatment is early detection, which can be achieved with CT (computed axial tomography) scans at regular intervals.

Eye Tumors

Up to 60% of people with von Hippel Lindau disease have retinal hemangioblastomas, a type of tumor that starts in the retina, a part of the eye that helps you see. The median age for people with VHL to develop a retinal hemangioblastomas is 25, although they can occur as early as 1 year. They can grow in both eyes or multiple sites within the same eye. Because tumors can occur when a person with VHL is young, it is essential that eye examinations start as early as possible, so appropriate treatment can be given.

Pancreas Tumors and Cysts

Between 20% and 50% of people with VHL develop cysts or serous cystadenomas in the pancreas. These cysts are benign and usually do not cause problems. Sometimes they grow large and press on surrounding pancreatic tissue or other organs in the body, causing blockage of the pancreas, pain or problems with other organs.

Pancreatic neuroendocrine tumors are found in 15% of patients with von Hippel Lindau disease. They often do not have symptoms. However, they may behave like true cancers and may spread to other organs in the body. Neuroendocrine tumors usually spread only if they grow larger than 3 centimeters (slightly more than 1 inch). The average age for people with VHL to develop pancreatic tumors or cysts is 35.

Von Hippel Lindau Disease Types

There are two major categories of VHL: type 1 and type 2. The main difference is that people with Type 1 disease rarely develop pheochromocytomas.

von Hippel Lindau disease is a genetic condition that runs in families. If you have von Hippel Lindau disease, or if you have a family history of the disease, we recommend genetic counseling. Visit our genetic testing page to learn more.

Sometimes von Hippel Lindau disease has no symptoms. When it does have signs, they vary from person to person and depend on the problems caused by the disease. These symptoms usually do not mean you have VHL. However, it is important to discuss any symptoms with your doctor, since they may signal other health problems.

Pheochromocytoma Symptoms

Pheochromocytomas may cause symptoms that are like what you feel in an emergency (“fight or flight”) situation. These include:

• High blood pressure, either all the time or just sometimes
• Sweating
• Headache
• Rapid or irregular heartbeats
• Feelings of anxiety, panic and fear
• Pale skin
• Dizziness or lightheadedness when you stand
• Tremor
• Weight loss

Hemangioblastoma Symptoms

Symptoms of hemangioblastomas vary depending on their location.

Cerebellum

• Difficulty walking and with muscle coordination
• Dizziness
• Headaches
• Double vision
• Vomiting

Spinal Cord

• Decreased feeling in the arms, legs and body
• Weakness
• Difficulty walking
• Difficulties with bowel and bladder function

Brain Stem

• Decreased feeling in the arms, legs and body
• Walking difficulties
• Swallowing difficulties
• Headaches
• Poor coordination

von Hippel Lindau disease is a genetic condition that runs in families. If you have von Hippel Lindau disease, or if you have a family history of the disease, we recommend genetic counseling. Visit our genetic testing page to learn more.

MD Anderson offers the most advanced diagnostic methods for von Hippel Lindau disease, including precise imaging techniques. In addition, we can provide comprehensive, expert genetic testing and counseling.

VHL can be challenging to diagnose. It often affects more than one part of the body, and the symptoms are often vague. However, finding von Hippel Lindau disease early may mean you have a higher chance for successful treatment and better quality of life. That’s why it’s important to be tested periodically if VHL runs in your family. Also, it’s a good idea for everyone in your family to have genetic testing.

If you have VHL and develop eye problems or signs of a neurological problem, such as headaches, your doctor may recommend a thorough eye exam or MRI or CT scans of the brain.

Getting a Second Opinion at MD Anderson

The experts at MD Anderson are highly experienced in diagnosing von Hippel Lindau disease and its associated conditions. We welcome the opportunity to provide second opinions.

von Hippel Lindau disease is a genetic condition that runs in families. If you have von Hippel Lindau disease, or if you have a family history of the disease, we recommend genetic counseling. Visit our genetic testing page to learn more.

Our Treatment Approach

Because VHL has the potential to cause a number of different problems, MD Anderson brings together a team of experts from several disciplines to treat the disease. They work together to personalize your care, ensuring the most-advanced and most-effective treatments possible.

Surgery, including minimally invasive and laser surgery in some cases, is the main treatment for VHL-associated problems. Like all surgeries, surgery for VHL disorders is most successful when performed by a specialist with a great deal of experience in the particular procedure.

MD Anderson’s surgeons are among the most skilled and renowned in the world. They perform a large number of surgeries for von Hippel Lindau disease each year, using the least-invasive and most-advanced techniques.

Our von Hippel Lindau Disease Treatments

If you are diagnosed with VHL, your treatment will depend on the problems it causes.

Pheochromocytoma

Surgery is the main treatment for pheochromocytomas. To prevent complications from severe high blood pressure caused by high catecholamine levels during surgery, you must take medicine for two to three weeks before the procedure.

Removal of a pheochromocytoma may require taking out the whole adrenal gland. This is called an adrenalectomy. Sometimes the surgeon can “spare” the cortex (outer layer) by removing only the tumor and the adrenal medulla. Sometimes, minimally invasive laparoscopic surgery, which uses a smaller incision and may help you recover quicker, is possible.

If both adrenal glands are removed, you will need to take medicine to give your body the hormones that usually are made by the adrenal gland.

Hemangioblastoma

If hemangioblastomas are small and/or slow-growing, they may not need treatment. Your doctor will observe the tumor and determine if you surgery is necessary. Tumors that are large, fast growing or symptom causing are surgically removed or treated with focused-beam or stereotactic radiation therapy.

Kidney Cancer

Kidney tumors usually are surgically removed when they grow larger than 3 centimeters in diameter or if they grow quickly. In addition, MD Anderson offers advanced treatments that can help some people, including:

• Partial nephrectomy, surgical removal of part of the kidney
• Radiofrequency ablation, which uses radiofrequency waves to destroy the tumor
• Cryoablation, which uses extreme cold to remove tissue

If kidney cancer spreads beyond the kidney, it becomes challenging to treat. Immunotherapy and chemotherapy help some people. New therapies include anti-angiogenesis (blood vessel starving) medications, which stop blood vessels from growing, and targeted therapies that help your body fight the disease on a molecular level.

Eye Tumors

It is important that eye problems caused by VHL receive early diagnosis and treatment. This helps lower the chance for vision loss.

Tumors found on the outer regions of the retina can be treated with laser photocoagulation (treatment with laser beams that heat and destroy tumors), or cryotherapy (treatment with extremely cold probes that destroy the tumor). Vitrectomy, or surgical treatment, should be considered for patients with detachment and/or scarring of the retina.

Tumors in very delicate areas, like the optic disc, usually are not treated because of the damage treatment might cause.

Pancreatic Cysts and Cystadenomas

Cysts and cystadenomas in the pancreas generally do not require treatment. Rarely, if a cyst becomes very large, your doctor may shrink it by using a needle to draw fluid from the cyst.

Pancreatic neuroendocrine tumors require close follow up because they may spread, which can be very dangerous. Generally, if a known or suspicious pancreatic neuroendocrine tumor becomes larger than 3 centimeters, it is surgically removed.

Our von Hippel Lindau Disease Clinical Trials

As one of the nation’s leading research centers, MD Anderson offers clinical trials of new treatments for von Hippel Lindau disease.