Review Question - QID 106435

This patient has symptomatic hypercalcemia due to malignancy. The next best step in management is to provide intravenous hydration as rapidly as possible. In general the management of hypercalcemia is: 1. IV fluids, 2. A loop diuretic, 3. A bisphosphonate for long term calcium control.

This patient's hypercalcemia is likely secondary to his metastatic prostate cancer. Malignancies can cause hypercalcemia via a number of different mechanisms, including osteolysis (e.g. multiple myeloma), parathyroid hormone related protein secretion (e.g. squamous cell carcinomas), ectopic parathyroid hormone secretion (e.g. lung cancers), and 1,25-dihydroxyvitamin D secretion (e.g. ovarian dysgerminomas). Immediate hydration enhances filtration and excretion of calcium.

Carroll and Schade acknowledge multiple other drugs that can be used to control the serum calcium level after hydration. However, they underscore that only when the intravascular volume has been restored should a loop diuretic be used in low dosages (e.g., furosemide, 10 to 20 mg). They further note that hypercalcemia of malignancy should be treated with bisphosphonates, because they target the underlying mechanism by decreasing osteoclast activity and promoting osteoclast apoptosis.

Strodel et al. note that primary hyperparathyroidism must not be ignored as a cause of hypercalcemia of malignancy. There is a higher incidence of primary hyperthyroidism in patients with cancer compared to the general population, and there is a higher incidence of cancer in patients with primary hyperthyroidism. Thus, serum parathyroid hormone level must be measured in all individuals presenting with hypercalcemia of malignancy even if another mechanism is suspected.

Incorrect Answers:
Answer 1: Bisphosphonates (e.g. pamidronate, zoledronic acid) are ultimately needed in management of hypercalcemia of malignancy if IV hydration is inadequate.
Answer 3: Calcitonin inhibits one resorption and augments calcium excretion. However, this drug is administered in hydration-refractory hypercalcemia.
Answer 4: Loop diuretics can be considered after IV hydration to inhibit calcium resorption in the distal convoluted tubule, but this is after hydration has been implemented.
Answer 5: Hemodialysis against a low-calcium dialysate can be considered in life-threatening hypercalcemia. However, more readily available interventions should be attempted before dialysis.