Hypercalcemia (High Level of Calcium in the Blood) - Hormonal and Metabolic Disorders - Merck Manual Consumer Version (original) (raw)

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, hypercalcemia leads to confusion and eventually coma. If not recognized and treated, the disorder can be life threatening.
• Usually, hypercalcemia is detected by routine blood tests.
• Drinking lots of fluids may be sufficient, but diuretics may increase calcium excretion, and medications can be used to slow the release of calcium from bone if needed.

(See also Overview of Electrolytes and Overview of Calcium's Role in the Body.)

Calcium is one of the body's electrolytes, which are minerals that carry an electric charge when dissolved in body fluids such as blood (but most of the body's calcium is uncharged). The body carefully controls the amount of calcium circulating in the blood.

Causes of Hypercalcemia

Causes of hypercalcemia 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 intake: Occasionally, hypercalcemia develops in people with peptic ulcers if they drink a lot of milk and take calcium-containing antacids for relief of the ulcer pain. The resulting disorder is called the milk-alkali syndrome.
• Too much vitamin D intake: 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 cancers of the kidney, lung, or ovary may secrete large amounts of a protein that, like parathyroid hormone, increases the calcium level in blood. These effects, called humoral hypercalcemia of malignancy, are considered a paraneoplastic syndrome. Calcium can also be released into the blood when cancer spreads (metastasizes) to bone and destroys bone cells. Such bone destruction occurs most commonly with cancers of the prostate, breast, or lung. 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 disease, bone is broken down, but the calcium level in blood is usually normal. However, the calcium level can become too high in people with Paget disease who become dehydrated or spend too much time sitting or lying down—when the bones are not bearing weight. Severe hyperthyroidism can also cause hypercalcemia by increasing resorption of bone tissue.
• Inactivity: Rarely, people who are immobilized, such as those who are paralyzed, 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.

Granulomatous disorders, such as sarcoidosis, tuberculosis, and leprosy, certain medications, endocrine disorders, and some other disorders may also cause hypercalcemia.

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

(See also Hyperparathyroidism.)

The parathyroid glands release parathyroid hormone, which

• Increases the absorption of calcium from the digestive tract
• Causes the kidneys to excrete less calcium
• Causes bones to release stored calcium

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.

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.

In 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 adults 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.

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.

In 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.

In tertiary hyperparathyroidism, excess parathyroid hormone is released regardless of the amount of calcium in the blood. Tertiary hyperparathyroidism usually occurs in people who have had long-standing secondary hyperparathyroidism.

Treatment depends on the cause.

The syndrome of familial hypocalciuric hypercalcemia is a hereditary disorder that results from the parathyroid glands underestimating the amount of calcium in the blood and, in response, mistakenly secreting too much parathyroid hormone. Parathyroid surgery is not useful in this disorder, and other treatment is usually not needed.

Symptoms of Hypercalcemia

Hypercalcemia often causes few symptoms. The earliest symptoms of hypercalcemia 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.

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.

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.

Diagnosis of Hypercalcemia

• Measurement of calcium level in the blood

Hypercalcemia is usually detected during routine blood tests.

Once hypercalcemia is detected, additional testing may be needed to determine the cause. Additional blood tests and urine tests may be done. A chest x-ray may also be needed to look for cancer or a lung disorder that can cause hypercalcemia. Genetic testing may be done when doctors are looking for a hereditary cause.

Treatment of Hypercalcemia

• Fluids and medications to increase excretion of calcium

When 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.

Doctors may advise people to take mineral supplements containing phosphate, which helps prevent calcium absorption.

If the calcium level is very high or if symptoms of brain dysfunction or muscle weakness appear, fluids and diuretics are given by vein (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 medications (including bisphosphonates, calcitonin, corticosteroids, and, rarely, plicamycin) can be used to treat hypercalcemia. These medications work primarily by slowing the release of calcium from bone.

Hypercalcemia caused by cancer is particularly difficult to treat. Sometimes a medication called denosumab is helpful. If the cancer cannot be controlled, hypercalcemia usually returns despite the best treatment.