Hypercalcemia is an abnormally high level of calcium in the blood, usually more than 10.5 milligrams per deciliter of blood.
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. Normally, the body maintains a balance between the amount of calcium in food sources and the calcium already available in the body's tissues. The balance can be upset if excess amounts of calcium are eaten or if the body is unable to process the mineral because of disease.
Calcium is one of the most important and most abundant minerals in the human body. Dairy products are the major source of calcium. Eggs, green leafy vegetables, broccoli, legumes, nuts, and whole grains provide smaller amounts. Only about 10-30% of the calcium in food is absorbed into the body. Most calcium is found in combination with other dietary components and must be broken down by the digestive system before it can be used. Calcium is absorbed into the body in the small intestine. Its absorption is influenced by such factors as the amount of vitamin D hormone available to aid the process and the levels of calcium already present in the body. 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. Circulating calcium plays an important role in the control of many body functions, such as blood clotting, transmission of nerve impulses, muscle contraction, and other metabolic activities. In the bloodstream, calcium maintains a constant balance with another mineral, phosphate.
Two main control agents are vital in maintaining calcium levels, vitamin D hormone and parathyroid hormone. A hormone is a chemical substance that is formed in one organ or part of the body and carried in the blood to another organ. It can alter the function, and sometimes the structure, of one or more organs.
- Parathyroid hormone (PTH). The four parathyroid glands are endocrine glands located next to the thyroid gland in the neck. A gland is a cell or group of cells that produces a material substance (secretion). When the level of calcium circulating in the blood drops, the parathyroid gland releases its hormone. PTH then acts in three ways to restore the normal blood calcium level. It stimulates the absorption of more calcium in the intestine; it takes more calcium from the bone tissue, and it causes the kidneys to excrete more phosphate.
- Vitamin D hormone. This hormone works with parathyroid hormone to control calcium absorption and affects the deposit of calcium and phosphate in the bone tissue.
The kidneys also help to control calcium levels. Healthy kidneys can increase calcium excretion almost fivefold to maintain normal concentrations in the body. Hypercalcemia can occur when the concentration of calcium overwhelms the ability of the kidneys to maintain balance.
Causes and symptoms
Causes of hypercalcemia
Many different conditions can cause hypercalcemia; the most common are hyperparathyroidism and cancer.
PRIMARY HYPERPARATHYROIDISM. Primary hyperparathyroidism is the excessive secretion of parathyroid hormone by one or more of the parathyroid glands. It is the most common cause of hypercalcemia in the general population. Women have this condition more frequently than men do, and it is more common in older people. It can appear thirty or more years after radiation treatments to the neck. Ninety percent of the cases of primary hyperparathyroidism are caused by a non-malignant growth on the gland.
Hyperparathyroidism can also occur as part of a rare hereditary disease called multiple endocrine neoplasia. In this disease, tumors develop on the parathyroid gland.
CANCER. People with cancer often have hypercalcemia. In fact, it is the most common life-threatening metabolic disorder associated with cancer. Ten to twenty percent of all persons with cancer have hypercalcemia. Cancers of the breast, lung, head and neck, and kidney are frequently associated with hypercalcemia. It also occurs frequently in association with certain cancers of the blood, particularly malignant myeloma. It is seen most often in patients with tumors of the lung (25-35%) and breast (20-40%), according to the National Cancer Institute. Cancer causes hypercalcemia in two ways. When a tumor grows into the bone, it destroys bony tissue (osteolysis). When the bone is not involved, factors secreted by cancer cells can increase calcium levels (humoral hypercalcemia of malignancy). The two mechanisms may operate at the same time.
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. Hormones and diuretics that increase the amount of fluid released by the body can also trigger hypercalcemia.
OTHER CAUSES. Other conditions can cause hypercalcemia. Excessive intake of vitamin D increases intestinal absorption of calcium. During therapy for peptic ulcers, abnormally high amounts of calcium antacids are sometimes taken. Over use of antacids can cause milk-alkali syndrome and hypercalcemia. Diseases such as Paget's, in which bone is destroyed or reabsorbed, can also cause hypercalcemia. As in cancer or paralysis of the arms and legs, any condition in which the patient is immobilized for long periods of time can lead to hypercalcemia due to bone loss.
Many patients with mild hypercalcemia have no symptoms and the condition is discovered during routine laboratory screening. Gastrointestinal symptoms include loss of appetite, nausea, vomiting, constipation, and abdominal pain. There may be a blockage in the bowel. If the kidneys are involved, the individual will have to urinate frequently during both the day and night and will be very thirsty. As the calcium levels rise, the symptoms become more serious. Stones may form in the kidneys and waste products can build up. Blood pressure rises. The heart rhythm may change. Muscles become increasingly weak. The individual may experience mood swings, confusion, psychosis, and eventually, coma and death.
High levels of calcium in the blood are a good indication of hypercalcemia, but these levels may fluctuate. Calcium levels are influenced by other compounds in the blood that may combine with calcium. Higher calcium and lower phosphate levels may suggest primary hyperparathyroidism. The blood levels of protein (serum albumin) and parathyroid hormone (PTH) are also measured in the diagnosis of hypercalcemia. Too much PTH in the blood may indicate primary hyperparathyroidism. Levels of calcium and phosphate in the urine should also be measured. The medical history and physical condition of the individual must be taken into consideration, especially in the early stages of hypercalcemia when symptoms are mild.
The treatment of hypercalcemia depends on how high the calcium level is and what is causing the elevation. Hypercalcemia can be life-threatening and rapid reduction may be necessary. If the patient has normal kidney function, fluids can be given by vein (intravenously) to clear the excess calcium. The amount of fluid taken in and eliminated must be carefully monitored. If the patient's kidneys are not working well, acute hemodyalysis is probably the safest and most effective method to reduce dangerous calcium levels. In this procedure, blood is circulated through tubes made of semi-permeable membranes against a special solution that filters out unwanted substances before returning the blood to the body.
Drugs such as furosemide, called loop diuretics, can be given after adequate fluid intake is established. These drugs inhibit calcium reabsorption in the kidneys and promote urine production. Drugs that inhibit bone loss, such as calcitonin, biphosphates, and plicamycin, are helpful in achieving long-term control. Phosphate pills help lower high calcium levels caused by a deficiency in phosphate. Anti-inflammatory agents such as steroids are helpful with some cancers and toxic levels of vitamin D.
Treatment of the underlying cause of the hypercalcemia will also correct the imbalance. Hyperparathyroidism is usually treated by surgical removal of one or more of the parathyroid glands and any tissue, other than the glands themselves, that is producing excessive amounts of the hormone.
The hypercalcemia caused by cancer is difficult to treat without controlling the cancer. Symptoms can be alleviated with fluids and drug therapy as outlined above.
Surgery to remove the parathyroid glands and any misplaced tissue that is producing excessive amounts of hormone succeeds in about 90% of all cases. Outcome is also influenced by whether any damage to the kidneys can be reversed.
Mild hypercalcemia can be controlled through good fluid intake and the use of effective drugs.
Hypercalcemia generally develops as a late complication of cancer and the expected outlook is grim without effective anticancer therapy.
People with cancer who are at risk of developing hypercalcemia should be familiar with early symptoms and know when to see a doctor. Good fluid intake (up to four quarts of liquid a day if possible), controlling nausea and vomiting, paying attention to fevers, and keeping physically active as much as possible can help prevent problems. Dietary calcium restriction is not necessary because hypercalcemia reduces absorption of calcium in the intestine.
"Hypercalcemia." National Cancer Institute Page. 〈http://www.nci.nih.gov〉.
Calcium— A silvery-yellow metal that is the basic element of lime and makes up about 3% of the earth's crust. It is the most abundant mineral in the human body. Calcium and phosphorous combine as calcium phosphate, the hard material of bones and teeth.
Hormone— A chemical substance that is carried through the blood to another part of the body, stimulating it to change its function or structure. Many hormones are produced by glands.
Metabolism— All the physical and chemical changes that take place within an organism.
Milk-alkali syndrome— A chronic disorder of the kidneys caused by the ingestion of large amounts of calcium and alkali in the treatment of peptic ulcer. The disorder is reversible in its early stages but can progress to kidney failure.
Mineral— A substance that does not contain carbon (inorganic) and is widely distributed in nature. Minerals play an important role in human metabolism.
Parathyroid hormone (PTH)— A chemical substance produced by the parathyroid glands. This hormone is a major element in regulating calcium in the body.
Vitamin D hormone— Vitamin D is a vitamin that also acts as a hormone. Vitamin D hormone acts with parathyroid hormone to regulate calcium levels in the blood and to supply appropriate amounts of calcium to all cells.
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:
- decreased muscle tone and muscle weakness
- delirium, disorientation, incoherent speech, and psychotic symptoms such as hallucinations and delusion
- poor appetite, nausea and/or vomiting
- frequency of urination and increased thirst
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.
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 hyper-calcemia. 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 hyper-calcemia 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.
Prucha, Edward J., ed. Cancer Sourcebook. Detroit: Omnigraphics, 2000.
Falk, Stephen, and Marie Fallon. "Emergencies." British Medical Journal (December 6, 1997): 1525
National Cancer Institute. Building 31, Room 10A31, 31 Center Drive, MSC 2580, Bethesda, MD 20892-2580. (800) 4-CANCER 5 July 2001<http://www.nci.nih.gov>
Deanna Swartout-Corbeil, R.N.
—A silvery-yellow metal that is the most abundant mineral in the human body. Calcium and phosphorous combine as calcium phosphate, the hard material of bones and teeth.
—An abnormally elevated blood calcium level caused by factors released from cancer cells, ultimately causing the loss of calcium from bone.
—An abnormally elevated blood calcium level caused by destruction of bone by a primary or metastatic tumor.