Hypercalcemia (PDQ�)

Introduction

This patient summary on hypercalcemia is adapted from the PDQ summary written for health professionals by cancer experts. This and other credible information about cancer treatment, screening, prevention, supportive care, and ongoing clinical trials is available from the National Cancer Institute. Hypercalcemia is a disorder in which the level of calcium in the blood is too high. Hypercalcemia is the most common life-threatening disorder associated with cancer. This brief summary describes hypercalcemia, its causes and treatment.

This summary is about hypercalcemia in adults with cancer.

Overview

Hypercalcemia occurs in 10%-20% of people with cancer, although it occurs much less often in children. The cancers most often associated with hypercalcemia are cancer of the breast and lung, as well as certain cancers of the blood, particularly multiple myeloma. Early diagnosis and treatment with fluids and drugs that lower calcium levels in the blood can improve symptoms in a few days, but diagnosis may be difficult. Symptoms of hypercalcemia can appear gradually and may resemble symptoms of many cancers and other diseases. Early diagnosis and treatment are not only lifesaving in the short term, but may also increase the patient's ability to complete cancer therapy and improve the patient's quality of life.

Patients who have advancedterminal cancer and are no longer receiving treatment for the cancer may choose not to be treated for hypercalcemia. This option should be considered by a patient and his or her family in advance, before symptoms of hypercalcemia occur.

Normal calcium regulation

Healthy people consume about the same amount of calcium in their diet as their bodies lose in urine, feces, and sweat. Hypercalcemia associated with cancer disrupts the body's ability to maintain a normal level of calcium.

Kidney function

Normal, healthy kidneys are able to filter large amounts of calcium from the blood, excrete the excess not needed by the body, and retain the amount of calcium the body does need. However, hypercalcemia may cause such high levels of calcium in the body that the kidneys are overworked and become unable to excrete the excess. Some tumors produce a substance that can cause the kidneys to excrete too little calcium. This results in a large amount of urine being produced, which then causes dehydration. Dehydration may lead to appetite loss, nausea, and vomiting, which make the dehydration worse. Inactivity caused by weakness and tiredness may increase the amount of calcium in the blood by increasing the amount of calcium that is absorbed from the bones. Calcium deposits may collect in the kidneys, causing permanent damage.

Causes

The main causes of hypercalcemia due to cancer are an increase in the amount of calcium absorbed from the bones, and an inability of the kidneys to excrete excess calcium. Some cancer cells secrete substances that cause calcium to be absorbed into the bloodstream from bones. Immobility, dehydration, anorexia, nausea, and vomiting may also increase calcium levels.

Incidence

Hypercalcemia occurs most frequently in patients with breast cancer, multiple myeloma, and lung cancer.

Symptoms

There is little relationship between symptoms of hypercalcemia and the actual level of calcium in the blood. Symptoms of hypercalcemia resemble symptoms of other illnesses, making an early and rapid diagnosis difficult. The severity of the symptoms may depend on other factors, such as previous cancer treatment, reactions to drugs, or other illnesses a patient may have.

Most patients do not experience all of the symptoms of hypercalcemia, and some patients may not have any symptoms at all. However, most patients with high calcium levels in the blood do have symptoms. Some patients develop signs of hypercalcemia when calcium levels are only slightly high, while patients who have had higher calcium levels for a long time may show few symptoms.

The most common symptoms of hypercalcemia are feeling tired, difficulty thinking clearly, lack of appetite, pain, frequent urination, increased thirst, constipation, nausea, and vomiting.

Symptoms may be classified by the affected body part:

Nervous system

Calcium plays a major role in the normal functioning of the central nervous system (the brain and spinal cord). Symptoms of hypercalcemia may include weakness, loss of reflexes in the muscles, and decreased stamina. Patients with central nervous system symptoms may have changes in personality, difficulty thinking or speaking clearly, disorientation, or hallucinations. Eventually, coma may result. Headaches can also occur, which can be made worse by vomiting and dehydration.

Heart

Hypercalcemia affects normal heart rhythms and increases sensitivity to some heart medications (such as digoxin). As calcium levels increase, irregular heartbeats may develop, and may lead to a heart attack.

Gastrointestinal

Increased stomach acid often is produced with hypercalcemia and may intensify loss of appetite, nausea, and vomiting. Constipation may result from the dehydration associated with hypercalcemia.

Kidney

Hypercalcemia causes the kidneys to not function correctly, leading to the production of large volumes of urine. The large amount of urine combined with less liquid intake leads to symptoms of dehydration, including thirst, dry mouth, little or no sweating, and concentrated urine. Patients with myeloma often have kidney problems due to hypercalcemia. Kidney stones may result from long-term hypercalcemia.

Bone

Hypercalcemia of cancer can result from bone metastases or bone loss, and may contribute to broken bones, bone disfigurement, and pain.

Assessment

Laboratory assessment

A blood test is done to check the level of calcium. Other blood tests may be done to check kidney function.

Clinical assessment

Patients with high calcium levels should be examined for the following:

• Symptoms:

  • Nerves and muscles (muscle strength, muscle tone, reflexes, tiredness, indifference, depression, confusion, restlessness).

  • Heart (high blood pressure, heart changes, irregular heartbeat, digitalis poisoning).

  • Kidneys (production of too much urine, night-time urinating, sugar in the urine, excess thirst).

  • Gastrointestinal (loss of appetite, nausea, abdominal pain, constipation, abdominal bloating).

  • Other (muscle and bone pain, itching).

• History:

  • How fast did the symptoms appear?

  • Is there x-ray evidence of primary or metastatic bone disease?

  • Has the patient been taking tamoxifen, estrogen, or androgens?

  • Is the patient taking digoxin?

  • Is the patient receiving calcium in intravenousfluids?

  • Is the patient receiving thiazide diuretics, vitamins A or D, or lithium?

  • Is there another disease present that could cause dehydration or lack of movement?

  • Are there effective treatments for the patient's cancer?

Decision to treat

The decision to treat hypercalcemia depends on the treatment goals determined by the patient, caregivers, and the physician. The natural course of untreated hypercalcemia progresses to loss of consciousness and coma. This may be preferred by some patients at the end of life who have unrelieved suffering and/or untreatable symptoms.

Treatment

Prevention

Patients at risk of developing hypercalcemia may be the first to recognize its symptoms, such as fatigue. Measures to prevent hypercalcemia include drinking enough fluids, controlling nausea and vomiting, walking and being active, and cautious use or elimination of drugs that can contribute to the development of hypercalcemia or affect its treatment. Calcium in the diet should not be reduced or eliminated, however, because the body's absorption of calcium is reduced in patients with hypercalcemia.

Managing hypercalcemia

Fluids are given to treat dehydration. Medication is given to stop the breakdown of bone. The cancer causing the hypercalcemia should be treated effectively.

The severity of the hypercalcemia determines the amount of treatment necessary. Severe hypercalcemia should be treated immediately and aggressively. Less severe hypercalcemia should be treated according to the symptoms. Response to treatment is shown by the disappearance of the symptoms of hypercalcemia and a decrease in the level of calcium in the blood.

Mild hypercalcemia does not usually need to be treated aggressively. Patients with mild hypercalcemia and central nervous system symptoms are harder to treat. Younger patients are especially difficult to treat because they tolerate hypercalcemia better. Other causes of the central nervous system symptoms should be ruled out before deciding that they are caused by hypercalcemia alone.

Treatment for hypercalcemia can improve symptoms. Increased urination and thirst, central nervous system symptoms, nausea, vomiting, and constipation improve with treatment more easily than other symptoms, such as loss of appetite, and tiredness. Pain may be more easily controlled once calcium levels are normal. Effective therapy that lowers calcium usually improves symptoms, enhances the quality of life, and may allow the patient to leave the hospital.

After calcium levels return to normal, urine and blood should continue to be checked often to make sure the treatment is still working.

Mild hypercalcemia

Giving fluids by vein and observing the patient is an accepted treatment for patients with mild hypercalcemia (but no symptoms) and who also have cancer that responds well to anticancer treatment (such as lymphoma, breast cancer, ovarian cancer, head and neck cancers, or multiple myeloma). If the patient has symptoms, or has a cancer that is expected to respond slowly to treatment, then drugs to treat the hypercalcemia should be started. Other treatments should focus on controlling nausea, vomiting, and fever, encouraging continued activity, and limiting use of drugs that cause sleepiness.

Moderate to severe hypercalcemia

Replacing fluids is the first and most important step in treating moderate or severe hypercalcemia. Replacing fluids will not restore normal calcium levels in all patients, but it is still important to do first. The patient's mental state should improve, and nausea and vomiting should decrease within the first 24 hours, but this improvement is only temporary. If cancer therapy (surgery, radiation, or chemotherapy) is not able to be started immediately, then drugs to lower the calcium levels must be used to control the hypercalcemia.

Drugs that may help stop the breakdown of bone include calcitonin, plicamycin (mithramycin), bisphosphonates (etidronate, pamidronate, and clodronate), and gallium nitrate. Steroids and phosphate may also be used to treat hypercalcemia. Dialysis is used as a treatment for hypercalcemia in patients with kidney failure. Other drugs are currently being studied as possible treatments for hypercalcemia. Combinations of drugs may also be used.

Patient and family education

Because hypercalcemia affects quality of life and can be life-threatening if not treated, patients and their caregivers should be aware of the symptoms. They should also learn how to prevent hypercalcemia, what can make it worse, and when to see the doctor.

Supportive care

Even with improved treatment for hypercalcemia, many patients do not survive this complication of cancer. Only effective anticancer therapy improves the patient's chances for long-term survival.

Supportive care includes measures to provide the patient with protection from injury, prevention of fractures, and treatment of symptoms.

Treatment of symptoms is important, especially the prevention of accidental or self-inflicted injury if a patient is confused. Nausea, vomiting, and constipation may also need to be controlled until calcium levels go down. Broken bones may occur due to weakening, so patients need to be moved gently, and falling must be prevented. Activity and weight-bearing exercises should be encouraged. Any new bone pain should be reported so that it can be evaluated for possible fractures.

Supportive care to comfort terminally ill patients and their family members becomes necessary in the last stages of the disease. Changes in the patient's thinking and behavior may especially upset the family.

Psychosocial management

Usually, treatment of the hypercalcemia will eliminate delirium, agitation, or mental changes, but some patients may need other medications to treat these symptoms. (See the PDQ summary on Cognitive Disorders and Delirium for more information.) Mental changes may take some time to get better, even after calcium levels return to normal.

Lethargy (mental and physical sluggishness) is often a symptom of hypercalcemia. Family members (and sometimes medical staff) may think that the patient is depressed until the actual cause is determined. Most patients will not have symptoms of depression (such as hopelessness, helplessness, guilt, worthlessness, or thoughts of suicide) and instead will appear to be indifferent.

Patients and family members should report symptoms of hypercalcemia such as lethargy, fatigue, confusion, loss of appetite, nausea/vomiting, constipation, and excessive thirst to the health care provider.

Prognosis

Hypercalcemia usually develops as a late complication of cancer, and its appearance is very serious. However, it is not clear if death occurs due to a hypercalcemia crisis (uncontrolled or one that comes back and gets worse) or due to the advanced cancer.

Current Clinical Trials

Check NCI?s list of cancer clinical trials for U.S. supportive and palliative care trials about hypercalcemia of malignancy that are now accepting participants. The list of trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

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Changes to This Summary (08/19/2011)

The PDQcancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Editorial changes were made to this summary.

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