MALIGNANCY-ASSOCIATED HYPERCALCEMIA - RELATIONSHIP BETWEEN MECHANISMS OF HYPERCALCEMIA AND RESPONSE TO ANTIHYPERCALCAEMIC THERAPY

Abstract

The pathophysiological mechanisms of hypercalcaemia were assessed in 50 rehydrated patients with cancer-associated hypercalcaemia. Surprisingly, renal tubular calcium reabsorption appeared to increase progressively as serum calcium rose, suggesting that the nomorgram used for the calculation may have been inaccurate, in absolute terms, probably due to its failure to take account of the levels of urinary sodium excretion. There were significant differences in the mechanisms of hypercalcaemia in different patient subgroups, however, independent of differences in urinary sodium excretion. In those with few or no bone metastases, increased renal tubular calcium reabsorption was the principal cause of hypercalcaemia, often in association with increased bone resorption. These abnormalities were thought to reflect the renal and skeletal actions of a tumour-associated humoral mediator. The main cause of hypercalcaemia in those with extensive metastatic bone disease was increased bone resorption, with contributions from impairment of glomerular filtration rate and, to a minor extent, increased renal tubular calcium reabsorption. These abnormalities were thought to reflect a mainly local-osteolytic mechanism of hypercalcaemia with secondary impairment of GFR. Of all the biochemical variables assessed pre-treatment, the renal tubular component of hypercalcaemia correlated most strongly with post-treatment serum calcium values (r = 0.61, P < 0.001). Because of their generally lower levels of renal tubular calcium reabsorption, patients with extensive skeletal metastases also had significantly lower post treatment calcium values than patients with few or no metastases (P < 0.05). These data indicate that the pathophysiological mechanisms of hypercalcaemia are a major determinant of the calcium lowering response after antihypercalcaemic treatment. This should be taken into account during comparative studies of antihypercalcaemia therapy in patients with malignancy.