Hypercalcemia

Definition

Hypercalcemia is an excessive amount of calcium in the blood.

Causes

Calcium is important in the body. It is an important part of the bone, and it exists as a charged particle called an ion in the blood and inside cells. Calcium is important to many body functions including bone formation, muscle contraction, nerve and brain function, and the release of hormones.

Parathyroid hormone (PTH) and vitamin D regulate calcium balance in the body. PTH is produced by the parathyroid glands -- four small glands located in the neck behind the thyroid gland. Vitamin D is obtained from exposure of skin to sunlight, and from dietary sources such as fortified dairy products, egg yolks, fish, and fortified cereals.

Primary hyperparathyroidism is the most common cause of hypercalcemia and is due to excess PTH. The drug lithium, used in treating bipolar disorder, may increase PTH release and cause hypercalcemia. A genetic mutation that affects the body's ability to regulate calcium is seen in familial hypocalciuric hypercalcemia (FHH), a benign (non-cancerous) condition.

Blood calcium can also be high despite low levels of PTH, however. Some malignant tumors (for example, lung cancers, breast cancer) produce PTH-related peptide (PTHrP) which increases blood calcium. Excess vitamin D (hypervitaminosis D) from diet or inflammatory diseases can also cause hypercalcemia. Kidney failure, adrenal gland  failure, hyperthyroidism

Hypercalcemia affects from 0.1 to 1% of the population. The widespread ability to measure blood calcium since the 1960s has improved detection of the condition, and today most patients with hypercalcemia have no symptoms. Women over the age of 50 are most likely to be hypercalcemic, usually due to primary hyperparathyroidism.

Symptoms

Skeletal:

• Bone pain
• Loss of height
• Bowing of the shoulders
• Spinal column curvature
• Pathological fractures

• Flank pain
• Frequent urination 
• Frequent thirst

• Pain 
• Nausea 
• Vomiting
• Poor appetite 
• Constipation

• Irritability 
• Memory loss 
• Apathy
• Depression
• Dementia
• Coma

• Weakness 
• Muscle twitches
• Muscle atrophy

Exams and Tests

• High serum total and/or ionized calcium 
• High serum PTH  level (hyperparathyroidism)
• High urine calcium (hyperparathyroidism, other causes)
• Low urine calcium (FHH)
• High vitamin D level (hypervitaminosis D, granulomatous diseases)
• High serum PTHrP (certain cancers)

Treatment

Treatment is directed at the underlying cause of hypercalcemia whenever possible. In cases of hyperparathyroidism, surgery may be needed to remove the abnormal parathyroid gland and cure the hypercalcemia.

When hypercalcemia is mild and caused by primary hyperparathyroidism, patients may be followed closely by their doctor over time. A new medication named cinacalcet has been shown to lower calcium levels in the blood by reducing parathyroid hormone production.

Severe hypercalcemia causing symptoms and requiring hospitalization is treated aggressively with the following:

• Intravenous fluids
• Bisphosphonates (drugs that stop bone breakdown and absorption by the body, such as pamidronate or etidronate)
• Calcitonin
• Glucocorticoids (steroids, for hypervitaminosis D that is not medication-related)
• Hemodialysis (for hypercalcemia that is unresponsive to treatment and is life-threatening)

Outlook (Prognosis)

Prognosis depends on the underlying cause of hypercalcemia. Patients with mild hyperparathyroidism or hypercalcemia with a treatable cause (for example, primary hyperparathyroidism, dietary hypervitaminosis D) may not suffer complications from hypercalcemia.

Patients with hypercalcemia secondary to conditions such as cancer or granulomatous disease may have a poor prognosis due to the underlying disease itself rather than to the hypercalcemia. The complications of prolonged hypercalcemia are uncommon today.

Possible Complications

Skeletal

• Fractures
• Osteoporosis
• Bone cysts

Kidney

• Nephrocalcinosis (calcification of the kidney)
• Kidney stones
• Dehydration
• Kidney failure

Gastrointestinal

• Pancreatitis
• Peptic ulcer disease
• Hypertension

Psychosocial

• Difficulty concentrating or thinking
• Depression

When to Contact a Medical Professional

Contact your physician or health care provider if you have a family history of hypercalcemia, family history of hyperparathyroidism, or if symptoms of hypercalcemia occur.

Prevention

Most causes of hypercalcemia cannot be prevented. Women over the age of 50 should see their health care provider regularly and have their blood calcium screened periodically.

Hypercalcemia from calcium and vitamin D supplements can be avoided by contacting your health care provider for advice if you are taking supplements without a prescription.

Taniegra ED. Hyperparathyroidism. Am Fam Physician. 2004; 69(2): 333-9.

Carroll MF. A practical approach to hypercalcemia. Am Fam Physician. 2003; 67(9): 959-66.

Ariyan CE. Assessment and management of patients with abnormal calcium. Crit Care Med. 2004; 32(4 Suppl): S146-54.