Hypercalcemia (PDQ®): Supportive care - Health Professional Information [NCI] - Management
Glucocorticoids have efficacy as hypocalcemic agents primarily in steroid-responsive tumors (e.g., lymphomas and myeloma) and in patients whose hypercalcemia is associated with increased vitamin D synthesis or intake (sarcoidosis and hypervitaminosis D).[Level of evidence: III];[Level of evidence: II] Glucocorticoids increase urinary calcium excretion and inhibit vitamin D–mediated gastrointestinal calcium absorption. Response, however, is typically slow; 1 to 2 weeks may elapse before serum calcium concentrations decrease. Oral hydrocortisone (100–300 mg) or its glucocorticoid equivalent may be given daily; however, complications of long-term steroid use limit its usefulness even in responsive patients.
Phosphate offers a minimally effective chronic oral treatment for mild to moderate hypercalcemia. It is most useful after successful initial reduction of serum calcium with other agents and should probably be reserved for patients who are both hypercalcemic and hypophosphatemic. The usual treatment is 250 to 375 mg per dose given 4 times daily (1–1.5 g of elemental phosphorus per day) to minimize the potential for developing hyperphosphatemia. Supranormal phosphate administration results in decreased renal calcium clearance and presumably decreases serum calcium concentrations by precipitating calcium into bone and soft tissues.[45,46][Level of evidence: II] Extraskeletal precipitation of calcium in vital organs may have adverse consequences and is especially significant after intravenous administration.;[47,48][Level of evidence: III] IV administration of phosphate produces a rapid decline in serum calcium concentrations but is rarely used because there are safer and more effective antiresorptive agents for life-threatening hypercalcemia (calcitonin and plicamycin). Hypotension, oliguria, left ventricular failure, and sudden death can occur as a result of rapid IV administration. Contraindications for phosphate include normophosphatemia, hyperphosphatemia, and renal insufficiency. Oral phosphate should be given at the lowest dose possible to maintain serum phosphorous concentrations lower than 4 mg/dL 1 to 2 hours after administration.
The use of phosphates is limited by individual patient tolerance and toxicity; 25% to 50% of patients cannot tolerate oral phosphates. Oral phosphate–induced diarrhea may be initially advantageous in patients who have experienced constipation secondary to hypercalcemia; it is the predominant and dose-limiting adverse effect for oral therapy and frequently prevents dosage escalation of more than 2 g of neutral phosphate per day.
Dialysis is an option for hypercalcemia that is complicated by renal failure. Peritoneal dialysis with calcium-free dialysate fluid can remove 200 to 2,000 mg of calcium in 24 to 48 hours and decrease the serum calcium concentration by 3 to 12 mg/dL (1.5–6 mEq/L or 0.7–3 mmol/L). Ultrafiltrable calcium clearance may exceed that of urea with calcium-free dialysate exchanges of 2 L each every 30 minutes. Hemodialysis is equally effective.[Level of evidence: III];[Level of evidence: IV] Because large quantities of phosphate are lost during dialysis and phosphate loss aggravates hypercalcemia, serum inorganic phosphate should be measured after each dialysis session, and phosphate should be added to the dialysate during the next fluid exchange or to the patient's diet.[Level of evidence: III] It is recommended, however, that phosphate replacement should be limited to restoring serum inorganic phosphate concentrations to normal rather than supranormal.