Chapter 8 - Hypercalcemia

Abstract

Hypercalcemia (defined as a serum calcium level> 10.5mg/dL or 2.5mmol/L) is an important clinical problem. Among the causes of hypercalcemia, primary hyperparathyroidism (PHP) and malignancy are most common, accounting for 80% to 90% of cases. PHP is the major cause of hypercalcemia in the ambulatory population, comprising up to 60% of cases, while malignancy represents the leading cause in hospitalized patients (54% to 65%). Hypercalcemia may occur in up to 30% of patients with cancer and portends a worse prognosis. The clinical presentation of hypercalcemia is influenced by the rapidity of onset as well as severity. Symptoms are nonspecific and include fatigue, weakness, nausea, vomiting, abdominal pain, bone pain, polyuria, and confusion, as well as coma in severe cases. Hypercalcemia may cause cardiac arrhythmias, renal vasoconstriction, volume depletion with acute kidney injury (AKI), and nephrogenic diabetes insipidus (NDI). Laboratory assessment begins with measurement of intact parathyroid hormone (iPTH) by immunoradiometric or immunochemiluminescent assay. An upper normal or elevated iPTH concentration is usually caused by PHP. However, familial hypocalciuric hypercalcemia (FHH) should be considered. A low or low-normal iPTH level (< 20pg/mL) is consistent with a PTH-independent process. Common conditions associated with hypercalcemia can be categorized into those with elevated parathyroid hormone (PTH) levels and those with PTH levels that are appropriately suppressed. PTH-dependent processes include PHPT caused by parathyroid gland adenoma or hyperplasia, rare cases of PTH-producing cancers, and FHH. PTH-independent mechanisms include most cases of malignancy-associated hypercalcemia (MAH), vitamin D intoxication, granulomatous diseases, vitamin A intoxication, thyrotoxicosis, milk-alkali syndrome, and immobilization.