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PREVIEW
A previous article by Dr Inzucchi (April, page 69) reviewed normal and abnormal calcium metabolism and examined the pathophysiologic features of hypercalcemia. In this article, Dr Inzucchi discusses the diagnostic evaluation of the patient with an elevated serum calcium concentration and presents appropriate therapeutic strategies.
The cause of hypercalcemia can be quickly ascertained in almost all cases after a complete clinical evaluation that includes selected biochemical tests, sometimes followed by focused radiographic studies.
Diagnostic evaluation
History taking and physical examination should concentrate on symptoms of hypercalcemia as well as those associated with hyperparathyroidism, malignancy, granulomatous disease, and other endocrinopathies. Possible signs of related conditions, such as osteoporotic fractures and renal colic, should also be explored. If medical records are available, the chronicity of the hypercalcemia should be examined, since the most common diagnosis, primary hyperparathyroidism, presents as mild, stable, or slowly progressive serum calcium elevation over a period of years. The patient's recent use of medications and supplements should be reviewed, and the family history should be probed for disorders of calcium metabolism as well as related endocrinopathies such as pituitary, adrenal, pancreatic, and thyroid neoplasia.
Laboratory tests
After the clinical assessment is made, laboratory tests should be used. The algorithm in figure 1 provides an overview of appropriate tests. Because elevated concentrations of plasma proteins may increase total calcium levels, it is important to rule out factitious hypercalcemia. About 50% to 60% of the calcium in the body is bound to plasma proteins, primarily albumin. Thus, in cases in which plasma proteins are elevated, such as in patients who have multiple myeloma, correction of the total serum calcium level must be made. Serum calcium concentration is lowered by 0.8 mg/dL (0.2 mmol/L) for every 1 mg/dL of albumin or protein above normal levels (similar to the opposite correction made for hypoalbuminemia). Alternatively, the ionized, or free, calcium concentration can be measured. Renal function should also be assessed. Once it is determined that the patient has hypercalcemia and normal renal function and is not taking any medications or supplements that elevate calcium levels, serum parathyroid hormone (PTH) concentration should be measured, along with serum calcium. It is also useful to measure serum phosphorus levels, electrolytes, and the amount of calcium in a 24-hour...