Monoclonal gammopathy of undetermined significance (MGUS)

Monoclonal gammopathy of undetermined significance, also called MGUS, is a condition caused by the development of altered plasma cells. A plasma cell is a type of white blood cell that usually produces disease-fighting antibodies.

In MGUS, plasma cells in bone marrow produce antibodies called monoclonal proteins that circulate in the blood. These antibodies also may be called M proteins, myeloma proteins or paraproteins.

MGUS is not itself a disease, but having MGUS increases the risk of developing cancer of the plasma cells and related conditions.

There is no treatment for MGUS. With regular checkups, a healthcare team monitors for changes in M protein levels, increases in altered plasma cells, and signs of cancer or other diseases.

People with MGUS usually don't have symptoms. Most often, the condition is found with blood tests done for regular checkups or for diagnosing another condition.

Experts don't know what causes MGUS. Genes within plasma cells may change because of a number of factors.

Factors that increase your risk of developing MGUS include:

• Age. Most people with MGUS are 70 or older.
• Race. Black people and people of African descent have a higher risk of MGUS than do other people. People of Asian descent appear to have a lower risk than do others.
• Sex assigned at birth. MGUS is more common in men.
• Family history. A family history of MGUS is an increased risk.
• Immune system risks. Having a weakened immune system is linked to an increased risk.
• Chemical exposure. Exposure to toxic chemicals in the workplace or environment — such as pesticides, asbestos and fertilizers — may increase the risk of MGUS.
• Other factors. Risk factors that may be lessened with lifestyle changes include cigarette smoking and obesity.

Each year, about 1% of people with MGUS develop cancer of the plasma cells or related conditions. These include the following:

• Multiple myeloma is cancer of the plasma cells in the bone marrow. This results in poor blood cell production, weakened bones and bone pain.
• Waldenstrom macroglobulinemia is a cancer of the plasma cells that produces excessive M proteins. This may cause thickened blood, bleeding, frequent infections, and an enlarged liver and spleen.
• Lymphomas are cancers that begin in a part of the immune system called the lymph system. Excessive white blood cell production can affect multiple body systems.
• Light chain amyloidosis is the buildup of proteins derived from M proteins. These amyloid proteins often build up in the heart, kidneys and nerve cells outside the brain.

Monoclonal gammopathies of clinical significance

M proteins may cause disease in tissues and change how organs function. If this type of M protein–related condition develops, it's called monoclonal gammopathy of clinical significance. Affected areas of the body may include the:

• Kidneys.
• Nervous system.
• Eyes.
• Skin.

Other complications

Other complications include:

• Osteoporosis. People with MGUS have an increased risk of osteoporosis. This condition is the loss of bone tissue. It makes bones fragile and likely to break.
• Risk of infections. MGUS increases the risk of viral and bacterial infections, especially infections of the nose, throat and lungs.
• Thromboembolism. MGUS also increases the risk of blood clots that circulate in the bloodstream and can block the flow of blood to tissues. This blockage is called a thromboembolism.

MGUS is usually discovered with blood tests done for other conditions or for regular checkups. When M proteins are found, you have more tests to better understand the condition and to see if there are signs of cancer or other organ damage. These tests include:

• Blood tests. Laboratory tests of blood samples tell your healthcare team more about the M proteins in your body and can show signs of organ damage.
• Urine tests. Urine samples taken over 24 hours can help show M proteins and signs of kidney damage.
• Imaging tests. You may have imaging tests of the whole body to rule out damage to the bone or changes in the bone marrow.
• Bone marrow test. A hollow needle removes a piece of bone marrow from the back of one of the hip bones for study. This test usually is only for those at risk of more-serious disease.
• Bone density test. You may have an X-ray test to measure the density of bone and detect signs of osteoporosis.

MGUS doesn't require treatment. Your care team schedules regular checkups to repeat blood and urine tests to find any increases in M proteins. You may have additional tests if a change in M proteins suggests an increased risk of cancer or other diseases.

Watchful waiting

You'll likely have a first follow-up exam within 3 to 6 months after a diagnosis of MGUS. Your healthcare team determines how often to repeat exams depending on the risk of MGUS leading to cancer or other diseases.

Talk with your healthcare professional if you have new symptoms. Symptoms to watch for include:

• Bone pain.
• Tiredness or weakness.
• Weight loss without trying.
• Fever with no apparent cause.
• Frequent infections.
• Tingling or numbness in legs or arms.
• Easy bruising or bleeding.
• Trouble breathing.
• Confusion or trouble thinking.

Medicines

If you develop osteoporosis, you may be prescribed a medicine called a bisphosphonate to slow the loss of bone tissue. Examples include alendronate (Binosto, Fosamax), risedronate (Actonel, Atelvia), zoledronic acid (Reclast, Zometa) and ibandronate.

Your healthcare professional may refer you to a doctor who specializes in blood conditions, called a hematologist.

Here's information to help you get ready for your appointment.

What you can do

Ask a family member or friend to go with you. Someone who's with you can help you remember the information you get.

Make a list of:

• Your symptoms and when they began. Include symptoms that don't seem linked to the reason you made the appointment.
• Key information, including other illnesses you or people in your family have had.
• All medicines, vitamins and supplements you take, including doses and the reasons for taking them.
• Questions to ask your healthcare professional.

For MGUS, basic questions to ask your health professional include:

• What tests do I need?
• Do I need to do something to get ready for tests?
• How often do I need to come back?
• Should I start treatment or change my lifestyle?
• I have other health conditions. How can I best manage these conditions together?

Be sure to ask all the questions you have.

What to expect from your doctor

Your healthcare professional is likely to ask you questions, including:

• Do your hands or feet tingle or feel numb?
• Have you had broken bones?
• Have you had a diagnosis of osteoporosis?
• Has someone in your family had MGUS or cancer of the blood?
• Have you ever had a blood clot?