Genetic Considerations

Hypercalcemia can be heritable through a number of different mechanisms. Mutation in the gene encoding the calcium-sensing receptor (CASR) gene results in familial hypocalciuric hypercal-cemia (HHC1) and for neonatal severe hyperparathyroidism. Gain-of-function mutations result in autosomal dominant hypocalcemia. Multiple endocrine neoplasia type I (MEN I) is an inherited disease usually resulting in enlargement of the parathyroid, pancreas, and pituitary glands. This disorder results in an increased lifetime risk of hyperparathyroidism.

Hypercalcemia can occur in any age group, in both sexes, and in all races and ethnicities. In infants, it can be caused by ingestion of large amounts of chicken liver or vitamin D or vitamin A supplements. Children and adolescents who consume large amounts of calcium-rich foods and drinks may develop hypercalcemia. Paget's disease, which causes increased bone turnover, leads to hypercalcemia in elderly people who are immobilized. Primary hyperparathyroidism causes most cases of hypercalcemia in people who are ambulatory and is more common in elderly women than in elderly men. Nearly 85% of cases result from an adenoma of a single parathyroid gland. The incidence in women older than 65 years is 250 per 100,000 each year. Hypercalcemia related to cancer have no sex predominance.

HISTORY. Determine a history of risk factors, with a particular focus on medications. Establish a history of anorexia, nausea, vomiting, constipation, polyuria, or polydipsia. Ask about muscular weakness or digital and perioral paresthesia (tingling) and muscle cramps. Ask family members if the patient has manifested personality changes.

PHYSICAL EXAMINATION. The signs and symptoms are directly related to the serum calcium level. In some patients, hypercalcemia is discovered upon routine physical examination. Evaluate the patient's neuromuscular status for muscle weakness, hypoflexia, and decreased muscle tone. Observe for signs of confusion. Hypercalcemia slows GI transit time; therefore, assess the patient for abdominal distension, hypoactive bowel sounds, and paralytic ileus. Strain the urine for renal calculi. Assess for fluid volume deficit by checking skin turgor and mucous membranes. Auscultate the apical pulse to determine heart irregularities.

PSYCHOSOCIAL. Increased calcium in the cerebrinospinal fluid may result in behavior changes. The symptoms can range from slight personality changes to the manifestations of psychosis. They may include mental confusion, impaired memory, slurred speech, or hallucinations. Assess the patient's mental status and the family's response to alterations in it.

Diagnostic Highlights

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