Renal calcium excretion is enhanced by saline infusion, because of both the increase in glomerular filtration rate and the role of the filtered load of sodium in blocking proximal tubular calcium reabsorption.90 The rate of infusion should be adjusted to the clinical situation. The uncertain cardiovascular status of these patients, many of whom are elderly, dictates caution. Infusion rates of 200 to 400 mL per hour of 0.9% saline are commonly used. The status of hydration should be checked frequently by physical signs (rales, skin turgor, mucous membrane hydration, blood pressure) and by hemodynamic monitoring when appropriate. Aggressive saline infusion may lead to hypokalemia, hypophosphatemia, and hypomagnesemia. These ions should be measured and replaced as necessary.

Loop diuretics appear to inhibit calcium reabsorption at the level of the thick ascending limb of the Henle loop.90 In theory, use of agents such as furosemide should enhance the calciuresis of a saline infusion. Furosemide in dosages of 40 mg or more,
given intravenously or orally, is widely used for this purpose. This drug should not be administered to dehydrated patients until rehydration is complete, because it may further reduce the glomerular filtration rate and, thereby, reduce the filtered load of calcium, decreasing renal calcium clearance even more. The drug is particularly useful if the patient has coexistent congestive heart failure. Again, careful surveillance of a patient’s fluid, electrolyte, and renal status during therapy is critical.

Dietary calcium and vitamin D restriction and avoidance of exposure to sunlight and other ultraviolet light sources is appropriate in patients with absorptive causes of hypercalcemia, such as sarcoidosis and other granulomatous diseases during their active stages.90 Dietary calcium intake should be kept at <400 mg per day, the use of vitamin D supplements should be discontinued, and the patient should be advised to limit sun exposure as much as possible. These same guidelines probably apply to the occasional patient with 1,25(OH)₂D-mediated hypercalcemia associated with lymphoma.32,33 and 34 Similarly, vitamin D intoxication and the milk-alkali syndrome should be treated with dietary calcium restriction.

Conversely, dietary calcium intake should not be reduced in patients with primarily resorptive, that is, malignancy-associated, hypercalcemia. Plasma 1,25(OH)₂D values are reduced in these patients, and dietary calcium absorption is inefficient. Unpalatable calcium-restricted diets are unnecessary and may further the nutritional deterioration and general misery of these patients.

Most causes of acute hypercalcemia requiring aggressive treatment are related to accelerated bone resorption. Therefore, agents that inhibit osteoclastic function are important aspects of therapy. Bone resorption in vivo and in vitro can be inhibited by calcitonin. Calcitonin use has been disappointing in treating moderate to severe hypercalcemia because it does not work in all patients. The decrease in serum calcium is generally small, and most patients escape from the osteoclast-inhibiting effects of calcitonin in several days. Furthermore, the treatment is extremely expensive.90,91 Nevertheless, given its low incidence of side effects and the rapidity with which the serum calcium level falls after administration of the hormone (2 to 4 hours), it is useful in some clinical settings. The dosage of salmon calcitonin suggested by the manufacturer is 4 IU/kg every 12 hours given subcutaneously or intramuscularly. Patients should undergo skin testing for hypersensitivity before use, as described in the package insert. Although interest has been shown in, and an argument made for, the synergistic effects of calcitonin and glucocorticoids, evidence supporting the efficacy of a combined regimen is not compelling (see Chap. 53).