Mild, asymptomatic hypercalcemia does not require immediate therapy, and management should be dictated by the underlying diagnosis. By contrast, significant, symptomatic hypercalcemia usually requires therapeutic intervention independent of the etiology of hypercalcemia. Initial therapy of significant hypercalcemia begins with volume expansion because hypercalcemia invariably leads to dehydration; 4–6 L of intravenous saline may be required over the first 24 h, keeping in mind that underlying comorbidities (e.g., congestive heart failure) may require the use of loop diuretics to enhance sodium and calcium excretion. However, loop diuretics should not be initiated until the volume status has been restored to normal. If there is increased calcium mobilization from bone (as in malignancy or severe hyperparathyroidism), drugs that inhibit bone resorption should be considered. Zoledronic acid (e.g., 4 mg intravenously over ∼30 min), pamidronate (e.g., 60–90 mg intravenously over 2–4 h), and etidronate (e.g., 7.5 mg/kg per day for 3–7 consecutive days) are approved by the U.S. Food and Drug Administration for the treatment of hypercalcemia of malignancy in adults. Onset of action is within 1–3 days, with normalization of serum calcium levels occurring in 60–90% of patients. Bisphosphonate infusions may need to be repeated if hypercalcemia relapses. Because of their effectiveness, bisphosphonates have replaced calcitonin or plicamycin, which are rarely used in current practice for the management of hypercalcemia. In rare instances, dialysis may be necessary. Finally, while intravenous phosphate chelates calcium and decreases serum calcium levels, this therapy can be toxic because calcium-phosphate complexes may deposit in tissues and cause extensive organ damage.
In patients with 1,25(OH)2D-mediated hypercalcemia, glucocorticoids are the preferred therapy, as they decrease 1,25(OH)2D production. Intravenous hydrocortisone (100–300 mg daily) or oral prednisone (40–60 mg daily) for 3–7 days are used most often. Other drugs, such as ketoconazole, chloroquine, and hydroxychloroquine, may also decrease 1,25(OH)2D production and are used occasionally.