About 99% of the body's calcium is stored in the bones, but cells (particularly muscle cells) and blood also contain calcium. Calcium is essential for the following:

• Formation of bone and teeth
• Muscle contraction
• Normal functioning of many enzymes
• Blood clotting
• Normal heart rhythm

The body precisely controls the amount of calcium in cells and blood. The body moves calcium out of bones into blood as needed to maintain a steady level of calcium in the blood. If people do not consume enough calcium, too much calcium is mobilized from the bones, weakening them. Osteoporosis can result. To maintain a normal level of calcium in blood without weakening the bones, people need to consume at least 1,000 to 1,500 milligrams of calcium a day. The level of calcium in blood is regulated primarily by two hormones: parathyroid hormone and calcitonin.

Parathyroid hormone is produced by the four parathyroid glands, located around the thyroid gland in the neck. When the calcium level in blood decreases, the parathyroid glands produce more parathyroid hormone. When the calcium level in blood increases, the parathyroid glands produce less hormone. Parathyroid hormone does the following:

• Stimulates bones to release calcium into blood
• Causes the kidneys to excrete less calcium in urine
• Stimulates the digestive tract to absorb more calcium
• Causes the kidneys to activate vitamin D, which enables the digestive tract to absorb more calcium

Calcitonin is produced by cells of the thyroid gland. It lowers the calcium level in blood by slowing the breakdown of bone, but only slightly.

Hypocalcemia

In hypocalcemia, the calcium level in blood is too low.

• A low calcium level may result from a problem with the parathyroid glands, as well as from diet, kidney disorders, or certain drugs.
• As hypocalcemia progresses, people may become confused, depressed, and forgetful and have tingling in their fingers and feet as well as stiff, achy muscles.
• Usually, the disorder is detected by routine blood tests.
• Calcium and vitamin D supplements may be used.

About 40% of the calcium in blood is attached (bound) to proteins in blood, mainly albumin. Protein-bound calcium acts as a reserve but has no active function in the body. Only unbound calcium affects the body's functions. Thus, hypocalcemia causes problems only when the level of unbound calcium is low. Unbound calcium has an electrical (ionic) charge, so it is called ionized calcium.

Causes

Hypocalcemia most commonly results when too much calcium is lost in urine or when not enough calcium is moved from bones into the blood. Causes of hypocalcemia include the following:

• A low level of parathyroid hormone (hypoparathyroidism), as can occur when the parathyroid glands are damaged during thyroid gland surgery
• Lack of response to a normal level of parathyroid hormone (pseudohypoparathyroidism)
• No parathyroid glands at birth
• A low level of magnesium (hypomagnesemia), which reduces the activity of parathyroid hormone
• Vitamin D deficiency (due to inadequate consumption or inadequate exposure to sunlight)
• Kidney dysfunction (a common cause), which results in more calcium excreted in urine and makes the kidneys less able to activate vitamin D
• Inadequate consumption of calcium
• Disorders that decrease calcium absorption
• Pancreatitis
• Certain drugs, including rifampin (an antibiotic), anticonvulsants (such as phenytoin and phenobarbital), bisphosphonates (such as alendronate, ibandronate, risedronate, and zoledronic acid), calcitonin, chloroquine, corticosteroids, and plicamycin

Symptoms

The calcium level in blood can be moderately low without causing any symptoms. Over time, hypocalcemia can affect the brain and cause neurologic or psychologic symptoms, such as confusion, memory loss, delirium, depression, and hallucinations. These symptoms disappear if the calcium level is restored.

An extremely low calcium level may cause tingling (often in the lips, tongue, fingers, and feet), muscle aches, spasms of the muscles in the throat (leading to difficulty breathing), stiffening and spasms of muscles (tetany), seizures, and abnormal heart rhythms.

Diagnosis

Hypocalcemia is often detected by routine blood tests before symptoms become obvious. Doctors measure the total calcium level (which includes calcium bound to albumin) and the albumin level in blood to determine whether the level of unbound calcium is low.

Blood tests are done to evaluate kidney function and to measure magnesium, phosphate, parathyroid hormone, and vitamin D levels. Other substances in blood may be measured to help determine the cause.

Treatment

Calcium supplements, given by mouth, are often all that is needed to treat hypocalcemia. If a cause is identified, treating the disorder causing hypocalcemia or changing drugs may restore the calcium level.

Once symptoms appear, calcium is usually given intravenously. Taking vitamin D supplements helps increase the absorption of calcium from the digestive tract. Thiazide diuretics may be given to decrease the excretion of calcium by the kidneys, particularly when hypocalcemia is caused by hypoparathyroidism.

Hypercalcemia

In hypercalcemia, the level of calcium in blood is too high.

• A high calcium level may result from a problem with the parathyroid glands, as well as from diet, cancer, or disorders affecting bone.
• At first, people have digestive problems, feel thirsty, and may urinate a lot, but if severe, the disorder can be life threatening.
• Usually, the disorder is detected by routine blood tests.
• Drinking lots of fluids may be sufficient, but diuretics may increase calcium excretion and drugs can be used to slow the release of calcium from bone if needed.

Causes

Causes include the following:

• Hyperparathyroidism: One or more of the four parathyroid glands secrete too much parathyroid hormone, which helps control the amount of calcium in blood.
• Too much calcium: Occasionally, hypercalcemia develops in people with peptic ulcers if they drink a lot of milk and take calcium-containing antacids for relief. The resulting disorder is called the milk-alkali syndrome.
• Too much vitamin D: If people take very high daily doses of vitamin D over several months, the amount of calcium absorbed from the digestive tract increases substantially.
• Cancer: Cells in kidney, lung, and ovary cancers may secrete large amounts of a protein that, like parathyroid hormone, increases the calcium level in blood. These effects are considered a paraneoplastic syndrome (see Symptoms and Diagnosis of Cancer: What Are Paraneoplastic Syndromes?). Calcium can also be released into blood when cancer spreads (metastasizes) to bone and destroys bone cells. Such bone destruction occurs most commonly with prostate, breast, and lung cancers. Multiple myeloma (a cancer involving bone marrow) can also lead to the destruction of bone and result in hypercalcemia. Other cancers can increase the calcium level in blood by means not yet fully understood.
• Bone disorders: If bone is broken down (resorbed) or destroyed, calcium is released into the blood, sometimes causing hypercalcemia. In Paget's disease, bone is broken down, but the calcium level in blood is usually normal. However, the calcium level can become too high if people with Paget's disease become dehydrated or spend too much time sitting or lying down—when the bones are not bearing weight.
• Inactivity: Rarely, people who are immobilized, such as paraplegics, quadriplegics, or people who must remain in bed for a long time, develop hypercalcemia because calcium in bone is released into the blood when bones do not bear weight for long periods of time.

What Is Hyperparathyroidism? The parathyroid glands release parathyroid hormone, which increases the absorption of calcium from the digestive tract and causes bones to release stored calcium. If the parathyroid glands release too much parathyroid hormone, hyperparathyroidism results. People with hyperparathyroidism have too much calcium and a normal or low level of phosphate in their blood. Parathyroid hormone causes the kidneys to excrete more phosphate, but it also causes the bones to release phosphate into the blood. The balance between these two effects determines whether the phosphate level remains normal or decreases. Primary hyperparathyroidism: An abnormality causes the release of too much parathyroid hormone. In about 90% of people with primary hyperparathyroidism, the abnormality is a noncancerous tumor (adenoma) in one of the parathyroid glands. In the remaining 10%, the glands simply enlarge and produce too much hormone. Rarely, cancers of the parathyroid glands cause hyperparathyroidism. Primary hyperparathyroidism is more common among women than among men. It is more likely to develop in older people and in people who have received radiation therapy to the neck. Sometimes it occurs as part of the syndrome of multiple endocrine neoplasia, a rare hereditary disorder (see Multiple Endocrine Neoplasia Syndromes). Primary hyperparathyroidism is usually treated by surgically removing one or more of the parathyroid glands. The goal is to remove all parathyroid tissue that is producing excess hormone. Surgery is successful in almost 90% of cases. Secondary hyperparathyroidism: Excess parathyroid hormone is released in response to a large decrease in the calcium level in blood, as can occur in chronic kidney disease and vitamin D deficiency. Treatment depends on the cause.

Did You Know... Lack of mobility can make the calcium level high because bones weaken and release calcium into the blood.

Symptoms and Diagnosis

Hypercalcemia often causes no symptoms. The earliest symptoms are usually constipation, nausea, vomiting, abdominal pain, and loss of appetite. People may excrete abnormally large amounts of urine, resulting in dehydration and increased thirst.

Very severe hypercalcemia often causes brain dysfunction with confusion, emotional disturbances, delirium, hallucinations, and coma. Muscle weakness may occur, and abnormal heart rhythms and death can follow. Long-term or severe hypercalcemia commonly results in kidney stones containing calcium. Less commonly, kidney failure develops, but it usually resolves with treatment. However, if enough calcium accumulates within the kidneys, damage is irreversible.

Hypercalcemia is usually detected during routine blood tests.

Treatment

If hypercalcemia is not severe, correcting the cause is often sufficient. If people have mild hypercalcemia or conditions that can cause hypercalcemia and if their kidney function is normal, they are usually advised to drink plenty of fluids. Fluids stimulate the kidneys to excrete calcium and help prevent dehydration.

If the calcium level is very high or if symptoms of brain dysfunction or muscle weakness appear, fluids and diuretics are given intravenously as long as kidney function is normal. Dialysis is a highly effective, safe, reliable treatment, but it is usually used only for people with severe hypercalcemia that cannot be treated by other methods.

Several other drugs (including bisphosphonates, calcitonin, corticosteroids, and, rarely, plicamycin) can be used to treat hypercalcemia. These drugs work primarily by slowing the release of calcium from bone.

Hypercalcemia caused by cancer is particularly difficult to treat. If the cancer cannot be controlled, hypercalcemia usually returns despite the best treatment.

Last full review/revision August 2008 by Larry E. Johnson, MD, PhD