Table V.

Treatment of hypercalcemia in WBS

Treatment	Indications	Response time	Monitoring*	Other considerations
Restriction of Ca and vitamin D to RDI	Ca >0.5 mg/dL above age-adjusted ULN	Days	Weekly Ca, phosphorus until at goal	In more severe cases (Ca >12 mg/dL or in patients admitted for treatment), restrict Ca to below RDI, using 25% below RDI as a starting point. Modest restriction of Ca intake that corrects hypercalcemia can be continued for several months as long as close clinical and laboratory monitoring are maintained. Long-term Ca restriction cautioned against.
Increase oral fluid intake, 2–2.5 L/m2/d	Ca >0.5 mg/dL above age-adjusted ULN	Days	Weekly Ca, phosphorus until at goal
IV hydration with normal saline bolus as needed, then continued fluids at 3 L/m2/d (typically D5 1/2 NS + 20 mEq/L KCl)	Ca >13 mg/dL or symptomatic	12–24 h	Telemetry, electrolytes	Reduce fluid rate in patients with congestive heart failure, renal failure, or hypertension. May be contraindicated in some. Consider further reduction in Ca/vitamin D intake at this time using medical formula.
Loop diuretics; furosemide 1 mg/kg up to every 12 h29	Continued elevated Ca following IV hydration within 24 h if Ca >14 mg/dL OR after 48 h of hydration if Ca remains >12 mg/dL	12–24 h	Monitor blood pressure Monitor potassium level	Volume expansion is required before and during diuretic therapy. Use with caution in renal/heart failure or nephrocalcinosis. Monitor closely for hypokalemia and hypotension, especially in patients with cardiovascular disease.
Bisphosphonates; pamidronate 1 mg/kg30–32	Continued Ca elevation >14 mg/dL following IV hydration and 24 h of diuretics OR after IV hydration and 48 h of diuretics if Ca still >12 mg/dL at that time OR if above treatments are contraindicated	24–72 h; duration 2–4 wk	Renal function panel, magnesium, phosphorus and Ca before and after infusion	Most commonly published treatment for persistent hypercalcemia in WS other than dietary restriction of Ca and hydration therapy. Nephrotoxic (use with caution in patients with renal failure). Risk of acute-phase reaction (low-grade fever, headache, nausea, emesis, rash, tachycardia, myalgia, bone pain). Hypocalcemia and hypophosphatemia may develop, so Ca and phosphorus should be checked before and after treatment. In most cases, a single dose is adequate, but the dose may need to be repeated in 1 mo if hypercalcemia recurs on a Ca-restricted diet.
Glucocorticoids; methylprednisolone 2 mg/kg/d29	Continued Ca elevation >14 mg/dL following IV hydration and 24 h of diuretics OR after IV hydration and 48 h of diuretics if Ca still > 12 mg/dL at that time OR if above treatments are contraindicated	2–5 d; duration days-weeks		A short course of glucocorticoids could be considered prior to bisphosphonates. Glucocorticoids are most effective in treatment of hypercalcemia related to inflammation but has been used in patients with WS. Prolonged therapy should be avoided as it may cause cushingoid features, osteoporosis and iatrogenic adrenal suppression.
Calcitonin 2–4 U/kg up to every 12 h30	Continued Ca elevation >14 mg/dL following IV hydration and 24 h of diuretics OR after IV hydration and 48 h of diuretics if Ca still >12 mg/dL at that time OR if above treatments are contraindicated	4–6 h; duration 48 h		Tachyphylaxis develops after 48 hours so response to therapy is short lived.
Dialysis	Only consider in patients refractory to above therapies with life-threatening hypercalcemia	Hours		May be needed in extreme cases where patients have contraindications to all above medical/fluid therapy or severe symptomatic levels of hypercalcemia.

^*Blood Ca levels should be followed in all patients, the frequency of which determined by the severity of hypercalcemia and expected rate of change with treatment. Ionized Ca, renal function panel, intact parathyroid hormone, 25-OH vitamin D, spot urine Ca/Cr and renal ultrasound should be obtained as part of an initial evaluation in patients with persistent or refractory to treatment mild hypercalcemia (Ca >0.5 mg/dL over normal limit but <12 mg/dL) and all patients with moderate to severe hypercalcemia (Ca >12 mg/dL).