What is hypercalcemia?

Related conditions:
Primary hyperparathyroidism, hyperthyroidism

Definition:
Hypercalcemia is a condition in which the calcium level in the blood is
above normal limits (total serum calcium greater than 10.5 milligrams/deciliter,
or mg/dl, in adults). Serum-ionized calcium and intracellular calcium
concentrations play a major role in many biologic activities, including bone
formation, hormone secretion, neurotransmitter release, muscle contraction, and
enzyme activities. Two hormones serve as primary regulators of calcium:
parathyroid hormone (PTH) and calcitonin. Parathyroid hormone stimulates the bones
to release calcium into the blood, while the thyroid gland produces calcitonin, a
hormone that slows the release of calcium. A condition of hypercalcemia reflects a
significant disturbance in this delicate balance.

Risk factors: Two fundamental types of genetic defects have been identified in parathyroid gland tumors: the overactivity of oncogenes and the loss of function of tumor-suppressor genes.

Etiology and the disease process: Causes of hypercalcemia can include the following:

• Primary hyperparathyroidism (excessive secretion of PTH)





• Malignancy (with and without bony metastasis)





• Cancers that produce blood dyscrasias: lymphoma, multiple myeloma, leukemia





• 
  Multiple
  endocrine neoplasias (MEN): hormone-producing
  tumors





• Granulomatous diseases: sarcoidosis, tuberculosis
  





• 
  Hyperthyroidism
  





• Vitamin D and vitamin A excess





• Medications: lithium therapy, thiazide diuretics





• Milk-alkali syndrome





• Severe, generalized immobilization





• Other conditions: Addison disease, peptic ulcer disease, hypophosphatasia, familial hypercalcemia

Primary hyperparathyroidism and malignancy account for nearly 90 percent of all cases of hypercalcemia.

Incidence: The annual incidence of hypercalcemia is estimated to be 0.2 percent in patients over the age of sixty, with an estimated prevalence of greater than 1 percent of the general population. It is estimated to affect 10 to 20 percent of people with cancer. The condition may manifest in subtle ways and have a benign course for many years or for a lifetime. It is more common in women than men by a ratio of 3:1.

Symptoms: In mild hypercalcemia, many patients do not exhibit symptoms. Patients with moderate hypercalcemia can complain of a constellation of symptoms involving the skeletal system (bones and muscles), the gastrointestinal tract, the kidneys, and the central nervous system. Severe symptoms (these associated with calcium levels of 13 to 15 mg/dl) include the following:

• Nausea and vomiting





• Anorexia





• Polydipsia (excessive thirst)





• Polyuria (frequent urination)





• Recurrent nephrolithiasis (formation of kidney stones)





• Profound muscle weakness (fatigue)





• Severe abdominal pain (constipation, peptic ulcer disease, pancreatitis)





• Muscle and joint ache





• Lethargy/fatigue





• Delirium (mental confusion) and psychosis





• Coma





• Cardiac arrhythmias (irregular heartbeat leading to cardiac arrest)

Screening and diagnosis: The current consensus is that simple medical
surveillance is appropriate for patients over fifty years of age when bone and
renal statuses are satisfactory. The immunoassay for parathyroid hormone (PTH) is
especially useful, reliable, and accurate in distinguishing major causes.

Diagnostic tests to confirm a diagnosis of hypercalcemia include PTH immunoassays (checking circulating levels of parathyroid hormone); serum calcium and creatinine tests, along with a twenty-four-hour urinary calcium test; and creatinine clearance tests. Selective imaging may employ the evaluation of bone density (X ray, computed tomography, or dual energy X-ray absorptiometry, or DEXA scans). Identification of soft-tissue masses is usually demonstrated by magnetic resonance imaging (MRI).

Treatment and therapy: In cases of severe hypercalcemia, individuals may need to be hospitalized to reduce calcium to a safe level. Treatment protocols include the following:

• Intravenous fluids





• Loop diuretic medications (furosemide-lasix) to flush excess calcium from the body and keep the kidneys functioning





• Intravenous bisphosphonates (drugs that inhibit bone breakdown)





• Calcitonin, a hormone produced by the thyroid gland to reduce bone resorption and slow bone loss





• Glucocorticoids to help counter the effects of vitamin D toxicity by
  inhibiting vitamin D conversion to calcitriol





• Mobilization to prevent bone resorption





• Hemodialysis (filtering of the blood to remove excess calcium)





• Surgery such as parathyroidectomy for primary
  hyperparathyroidism

The critical management question is whether the disease should be treated
surgically. A 30 percent reduction in creatinine clearance, a twenty-four-hour
urinary calcium of greater than 400 mg, and an elevated serum calcium level are
persuasive factors. Traditionally, surgery (for hyperparathyroidism) has involved
an extensive cervical incision and general anesthesia. A newer technique
(radioguided parathyroidectomy) is now available. In this procedure, a
radioisotope scan is performed preoperatively to locate the abnormal parathyroid
gland. The operation is performed in less than an hour through a 1-inch incision.
All surgery poses some risks. A small percentage of people undergoing this
intervention can experience damage to the nerves controlling the vocal cords, and
some develop a chronically low calcium level requiring lifelong supplements of
calcium and vitamin D.

Prognosis, prevention, and outcomes: Calcium metabolism is carefully
and strictly regulated within a narrow range (8.5 to 10.2 mg/dl). Too much
calcium, for whatever reason, can interfere with essential life processes.
Conservative care is indicated for mild to moderate electrolyte disturbances, but
surgery is a viable treatment option and should be considered in conditions
related to hyperparathyroidism and malignancy.

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