Hypercalcemia

Definition

Hypercalcemia is an abnormally high level of calcium in the blood, usually more than 10.5 milligrams per deciliter of blood.

Description

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.

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.

• 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.

Causes & symptoms

Causes of hypercalcemia

Many different conditions can cause hypercalcemia; the most common are hyperparathyroidism and cancer.

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.

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 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.

Common symptoms

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.

Diagnosis

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.

Treatment

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.

Prognosis

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.

Prevention

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.

Key Terms

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.

Further Reading

For Your Information

Books

• Shils, Maurice E. et al. Modern Nutrition in Health and Disease. Philadelphia: Lea & Febiger, 1994.
• Williams, Sue Rodwell. Essentials of Nutrition and Diet Therapy. Philadelphia: Mosby, 1997.

  Other

• National Cancer Institute. Hypercalcemia. 1998. http://www.graylab.ac.uk/cancernet/304462.html.

Gale Encyclopedia of Medicine. Gale Research, 1999.