End-organ resistance to PTH infusion in hypercalcaemic and normocalcaemic patients with solid tumours

Ten hypercalcaemic patients with solid tumours were studied to evaluate the renal response on PTH infusion as assessed by nephrogenous cAMP excretion and maximum tubular re-absorption of phosphate. In addition, 20 normocalcaemic patients, 11 with an adenocarcinoma and 9 with a squamous cell carcinoma, were studied. All cancer patients had moderately extensive disease. Results were compared with those of 9 patients with primary hyperparathyroidism and with 10 elderly controls. All groups studied had comparable renal function, magnesium and 25-hydroxy-vitamin D levels. Comparable results were obtained in patients with an adenocarcinoma and in controls. cAMP response (Δ nephrogenous cAMP) was significantly lower in the hypercalcaemic patients with a solid tumour compared with the controls (8.13 ± 4.68 nmol/100 ml glomerular filtrate vs 29.52 ± 25.62 nmol/100 ml glomerular filtrate; P < 0.005). In the group of patients with primary hyperparathyroidism Δ nephrogenous cAMP was 13.41 ± 7.54 nmol/100 ml glomerular filtrate (P < 0.06 vs controls). The group of patients with a squamous cell cancer showed an intermediate value of 14.83 ± 10.74 nmol/100 ml glomerular filtrate (P < 0.025 vs the normocalcaemic adenocarcinoma patients, but NS vs controls). In two hypercalcaemic patients with a solid tumour in whom PTH infusion was repeated after normalization of serum calcium no influence on renal responsiveness was observed. Responses of maximum tubular re-absorption of phosphate were lowest in the group of hypercalcaemic patients with a solid tumour and in the patients with primary hyperparathyroidism compared with controls (0.11 ± 0.10 vs 0.22 ± 0.09 mmol/l and 0.09 ± vs 0.22 ± 0.09 mmol/l; P <0.025 and P <0.005, respectively). It is concluded that in hypercalcaemic patients with a solid tumour a humoral factor is present which inhibits the interaction of exogenous PTH and its renal receptors. In a subset of normocalcaemic patients with a squamous cell cancer the same circulating factor might be present.