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Diagnostic approach to hypercalcemia

Elizabeth Shane, MD
Section Editor
Clifford J Rosen, MD
Deputy Editor
Jean E Mulder, MD


Hypercalcemia is a relatively common clinical problem. Among all causes of hypercalcemia, primary hyperparathyroidism and malignancy are the most common, accounting for greater than 90 percent of cases [1-3]. Therefore, the diagnostic approach to hypercalcemia typically involves distinguishing between the two.

It is usually not difficult to differentiate between them. Malignancy is often evident clinically by the time it causes hypercalcemia, and patients with hypercalcemia of malignancy usually have higher calcium concentrations and are more symptomatic from hypercalcemia than individuals with primary hyperparathyroidism. Although hypercalcemia in otherwise healthy outpatients is usually due to primary hyperparathyroidism and malignancy is more often responsible for hypercalcemia in hospitalized patients, other potential causes of hypercalcemia must be considered (table 1).

This topic will review the diagnostic approach to hypercalcemia. The clinical manifestations, etiology, and treatment are reviewed separately. (See "Clinical manifestations of hypercalcemia" and "Etiology of hypercalcemia" and "Treatment of hypercalcemia".)


The first step in the evaluation of a patient with hypercalcemia is to verify with repeat measurement (total calcium corrected for albumin) that there is a true increase in the serum calcium concentration. If available, previous values for serum calcium should also be reviewed. The presence of longstanding asymptomatic hypercalcemia is more suggestive of primary hyperparathyroidism and also raises the much less common possibility of familial hypocalciuric hypercalcemia.

The degree of hypercalcemia also may be useful diagnostically. Primary hyperparathyroidism is often associated with borderline or mild hypercalcemia (serum calcium concentration often below 11 mg/dL [2.75 mmol/L]). Values above 13 mg/dL (3.25 mmol/L) are unusual in primary hyperparathyroidism, although they do occur and are more common in patients with malignancy-associated hypercalcemia. (See "Primary hyperparathyroidism: Diagnosis, differential diagnosis, and evaluation" and "Disorders of the calcium-sensing receptor: Familial hypocalciuric hypercalcemia and autosomal dominant hypocalcemia" and "Hypercalcemia of malignancy: Mechanisms".)

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Literature review current through: Nov 2017. | This topic last updated: Nov 01, 2016.
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