Hypercalcemia in patients with metastatic renal cell carcinoma: effect of nephrectomy and metabolic evaluation

The role of nephrectomy in the management of hypercalcemia in metastatic renal carcinoma is not known. Hypercalcemia in patients with renal cell carcinoma frequently mimics primary hyperparathyroidism and has been attributed to tumor secretion of parathyroid hormone related protein. We determined the role of cytoreductive surgery in patients with metastatic renal cell carcinoma and hypercalcemia, identified factors that predict patient benefit from surgery, and evaluated the mechanisms of hypercalcemia in these patients.

A total of 15 patients with metastatic renal cell carcinoma and hypercalcemia underwent metabolic and laboratory evaluation followed by nephrectomy. Post-operatively they were followed for changes in serum calcium levels. We selected 18 normocalcemic patients with metastatic renal cell carcinoma and 4 normocalcemic patients without renal cancer to serve as control groups for survival and parathyroid hormone related protein expression.

A decrease in serum calcium corrected for albumin occurred in 9 of 11 patients at 1 to 4 weeks after nephrectomy and in 7 of 12 patients at 5 to 16 weeks after nephrectomy. Clinical evaluation supported a parathyroid hormone related protein mechanism of hypercalcemia in 5 of 8 patients. Two patients had evidence of local osteolytic hypercalcemia and 1 had prostaglandin mediated hypercalcemia.

Nephrectomy temporarily ameliorated hypercalcemia in a subgroup of patients with metastatic renal cancer and hypercalcemia. Parathyroid hormone related protein expression was commonly found to be associated with hypercalcemia. Nonparathyroid hormone related protein mechanisms of hypercalcemia in renal carcinoma may be more common than previously thought.