Diagnostic approach to hypercalcemia
- Elizabeth Shane, MD
Elizabeth Shane, MD
- Professor of Medicine
- Columbia University College of Physicians and Surgeons
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 card 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".)
INTERPRETATION OF SERUM CALCIUM
In almost all patients, hypercalcemia is due to an elevation in the physiologically important ionized (or free) calcium concentration. However, 40 to 45 percent of the calcium in serum is bound to protein, principally albumin; as a result, increased protein binding can cause an elevation in the serum total calcium concentration without any rise in the serum ionized calcium concentration. Patients in whom this can occur include those with hyperalbuminemia due to severe dehydration and rare patients with multiple myeloma who have a calcium-binding paraprotein. This phenomenon is called pseudohypercalcemia (or factitious hypercalcemia), since the patient has a normal ionized serum calcium concentration.
Alternatively, in patients with hypoalbuminemia due to chronic illness or malnutrition, total serum calcium concentration may be normal when serum ionized calcium is elevated. Thus, in patients with hypo- or hyperalbuminemia, the measured calcium concentration should be corrected for the abnormality in albumin (calculator 1) or for standard units (calculator 2). If a laboratory known to measure ionized calcium reliably is available, some authorities prefer to measure the serum ionized calcium in this situation. (See "Relation between total and ionized serum calcium concentrations".)
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