Intravenous phosphate administration is probably the fastest and surest way to reduce serum calcium, but it is a hazardous procedure if not done properly. Intravenous phosphate should be used only after other methods of treatment (bisphosphonates, calcitonin, and saline diuresis) have failed to control symptomatic hypercalcemia. Phosphate must be given slowly (50 mmol or 1.5 g elemental phosphorus over 6–8 hours) and the patient switched to oral phosphate (1–2 g/d elemental phosphorus, as one of the salts indicated below) as soon as symptoms of hypercalcemia have cleared. The risks of intravenous phosphate therapy include sudden hypocalcemia, ectopic calcification, acute renal failure, and hypotension. Oral phosphate can also lead to ectopic calcification and renal failure if serum calcium and phosphate levels are not carefully monitored, but the risk is less and the time of onset much longer. Phosphate is available in oral and intravenous forms as sodium or potassium salts. Amounts required to provide 1 g of elemental phosphorus are as follows:
Intravenous:
In-Phos, 40 mL; or Hyper-Phos-K, 15 mL
Oral:
Fleet Phospho-Soda, 6.2 mL; or Neutra-Phos, 300 mL; or K-Phos-Neutral, 4 tablets
Glucocorticoids have no clear role in the immediate treatment of hypercalcemia. However, the chronic hypercalcemia of sarcoidosis, vitamin D intoxication, and certain cancers may respond within several days to glucocorticoid therapy. Prednisone in oral doses of 30–60 mg daily is generally used, although equivalent doses of other glucocorticoids are effective. The rationale for the use of glucocorticoids in these diseases differs, however. The hypercalcemia of sarcoidosis is secondary to increased production of 1,25(OH)2D by the sarcoid tissue itself. Glucocorticoid therapy directed at the reduction of sarcoid tissue results in restoration of normal serum calcium and 1,25(OH)2D levels. The treatment of hypervitaminosis D with glucocorticoids probably does not alter vitamin D metabolism significantly but is thought to reduce vitamin D–mediated intestinal calcium transport and increase renal excretion of calcium. An action of glucocorticoids to reduce vitamin D–mediated bone resorption has not been excluded, however. The effect of glucocorticoids on the hypercalcemia of cancer is probably twofold. The malignancies responding best to glucocorticoids (ie, multiple myeloma and related lymphoproliferative diseases) are sensitive to the lytic action of glucocorticoids. Therefore part of the effect may be related to decreased tumor mass and activity. Glucocorticoids have also been shown to inhibit the secretion or effectiveness of cytokines elaborated by multiple myeloma and related cancers that stimulate osteoclastic bone resorption. Other causes of hypercalcemia—particularly primary hyperparathyroidism—do not respond to glucocorticoid therapy.