Key Terms: Calcium, Humoral hypercalcemia.
Description
Hypercalcemia is an abnormally high level of calcium in the blood, usually more than 10.5 milligrams per deciliter of blood. It is the most common life-threatening metabolic disorder associated with cancer.
Calcium plays an important role in the development and maintenance of bones in the body. It is also needed in tooth formation and is important in other body functions. As much as 99% of the body's calcium is stored in bone tissue. A healthy person experiences a constant turnover of calcium as bone tissue is built and reshaped. The remaining 1% of the body's calcium circulates in the blood and other body fluids. Calcium in the blood plays an important role in the control of many body functions, including blood clotting, transmission of nerve impulses, muscle contraction, and other metabolic activities.
Cancer-caused hypercalcemia produces a disruption in the body's ability to maintain a normal level of calcium. This abnormally high level of calcium in the blood develops because of increased bone breakdown and release of calcium from the bone. The disorder occurs in approximately 10-20% of all cancer cases. The most common cancers associated with hypercalcemia are breast, prostate, and lung cancer, as well as multiple myeloma or other tumors with extensive metastasis to the bone. It may also occur in patients with head and neck cancer, cancer of unknown primary, lymphoma, leukemia, kidney cancer, and gastrointestinal cancer. Hypercalcemia most commonly develops as a late complication of cancer, and its appearance constitutes an emergency.
Several clinical symptoms are associated with cancer-related hypercalcemia. Symptoms may appear gradually and often look like signs of other cancers and diseases. The symptoms of hypercalcemia are not only related to the elevated level of calcium in the blood, but—more importantly—to how rapidly the hypercalcemia develops. The severity of the symptoms is often dependent upon factors such as previous cancer treatment, reactions to medications, or other illnesses a patient may have. Most patients do not experience all of the symptoms of hypercalcemia, and some may not have any signs at all. Rapid diagnosis of hypercalcemia may be complicated because the symptoms are often nonspecific and are easily ascribed to other factors. These symptoms include:
Causes
The fundamental cause of cancer-related hypercalcemia is increased movement of calcium out of the bones and into the bloodstream, and secondarily, an inadequate ability of the kidneys to get rid of higher calcium levels. Normally, healthy kidneys are able to filter out large amounts of calcium from the blood, getting rid of the excess that is unneeded by the body and keeping the amount of the calcium the body does need. However, the high levels of calcium in the body caused by cancer-related hypercalcemia may cause the kidneys to become overworked, thus making them unable to excrete the excess. Another problem is that some tumors produce a substance that may cause the kidneys to get rid of too little calcium.
Two types of cancer-caused hypercalcemia have been identified: osteolytic and humoral. Osteolytic occurs because of direct bone destruction by a primary or metastatic tumor. Humoral is caused by certain factors secreted by malignant cells, which ultimately cause calcium loss from the bones. Certain types of hormonal therapy may precipitate hypercalcemia and the use of some diuretics may contribute to the disorder.
Because immobility causes an increase in the loss of calcium from bone, cancer patients who are weak and spend most of their time in bed are more prone to hypercalcemia. Cancer patients are often dehydrated because they take in inadequate amounts of food and fluids and often suffer from nausea and vomiting. Dehydration reduces the ability of the kidneys to remove excess calcium from the body, and therefore is another contributing factor in the development of hypercalcemia in cancer patients.
Treatments
Individuals at risk for developing hypercalcemia may be the first to recognize symptoms, such as fatigue. The patient and family should be aware of the signs and symptoms so that a health care professional can be notified as early as possible should they occur. Patients can take several preventative measures like ensuring adequate fluid intake, controlling nausea and vomiting, maintaining the highest possible mobility, and avoiding drugs that affect the functioning of the kidneys. This includes avoiding those medications containing calcium, vitamin D, or vitamin A. Since absorption of calcium is usually decreased in individuals with hypercalcemia, dietary calcium restriction is unnecessary.
The mortality rate for untreated hypercalcemia is quite high. Early diagnosis and prompt treatment are essential. The magnitude of hypercalcemia and the severity of symptoms is usually the basis for determining what type of treatment is indicated.
For those patients who have mild hypercalcemia, are experiencing no symptoms, and have cancer that is responsive to treatment, giving intravenous fluids and observing the patient may be all that is necessary to treat the condition. If the patient is experiencing symptoms or has a cancer that is expected to respond poorly to treatment, then medication to treat the hypercalcemia should be initiated. Additional treatment focuses on controlling nausea and vomiting, encouraging activity, and avoiding any medication that causes drowsiness.
In treating moderate or severe hypercalcemia, replacing fluids is the first treatment intervention. Though providing fluid replacement will not restore normal calcium levels in all patients, it is still the most important initial step. Improvement in mental status and nausea and vomiting is usually apparent within 24 hours for most patients. However, rehydration is only a temporary measure. If the cancer is not treated, then drugs that will help to control the hypercalcemia are necessary. Many drugs are used to treat hypercalcemia, including calcitonin, plicamycin (formerly mithramycin), gallium nitrate, and bisphosphonates. Bisphosphonates are some of the most effective drugs for controlling hypercalcemia. Loop diuretics like furosemide are often given because they help to increase the excretion of excess serum calcium. For severe hypercalcemia that is complicated by kidney failure, dialysis is an option. Because of the large amounts of intravenous fluids given to treat hypercalcemia, the health care team will carefully observe for any signs of overhydration or other electrolyte imbalances.
The severity of 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. A positive response to the treatment is exhibited by the disappearance of the symptoms and a decreased level of calcium in the blood. Mild hypercalcemia does not usually need to be treated aggressively. After calcium levels return to normal, urine and blood should continue to be checked often to make certain the treatment is still working.
Alternative and Complementary Therapies
There are no known proven alternative treatments for cancer-related hypercalcemia. Some of the medications used are more effective than others, and the patient and family should discuss which ones are the most appropriate for the patient's needs.
Hypercalcemia usually develops as a late complication of cancer, and its appearance is very serious. The outlook is often quite grim. However, it is not clear if death occurs because of the hypercalcemia crisis or because of the advanced cancer. Because hypercalcemia is often a complication that occurs in the final stages of cancer, the decision to treat it depends upon the overall goals of treatment determined by the patient, family, and physician. The natural course of untreated hypercalcemia will progress to loss of consciousness and coma. Some patients may prefer this at the end of life rather than have unrelieved suffering and/or untreatable symptoms. It is therefore important for the patient and caregivers to discuss what supportive care measures are wanted.
Resources
Books
Prucha, Edward J., editor. Cancer Sourcebook. Detroit: Omnigraphics, 2000.
Other
National Cancer Institute. Building 31, Room 10A31, 31 Center Drive, MSC 2580, Bethesda, MD 20892-2580. (800) 4-CANCER. [cited July 5, 2005]. .
—Deanna Swartout-Corbeil, R.N.
