A study of prostaglandin E₂, parathormone, and response to indomethacin in patients with hypercalcemia of malignancy

In order to evaluate the relationship of PGE₂ to hypercalcemia in cancer patients, 101 patients were screened with a radioimmunoassay for plasma prostaglandin E₂ (PGE₂) (NL < 100 pg/ml). Of the 101 patients, 31 were hypercalcemic. Mean PGE₂ (±SEM) of the 31 patients was 199 ± 36 pg/ml. Among the 70 normocalcemic patients, mean ± SEM PGE₂ was 85 ± 12 pg/ml (range = <25–225 pg/ml) (P < 0.001). Seventeen hypercalcemic patients were initially treated with saline and furosemide, then were prospectively screened for serum parathormone (iPTH) and PGE₂. Fourteen of 17 patients were then treated empirically with indomethacin (25 mg b.i.d.) for 72 hours and the PGE₂ assay was repeated. Prior to therapy with indomethacin (mean ± SEM), Ca⁺⁺ = 12.2 ± 1.5 mg/dl (NL 8.4–10.6 mg/dl), PGE₂ = 87.1 ± 36.8 pg/ml, (range = <25–209 pg/ml), and iPTH = 406 ± 266 pg/ml (NL < 400 pg/ml) (range = <100–825 pg/ml). PGE₂ was elevated before treatment in 6/14 patients (breast, colon, renal, lung, neck tumors, and myeloma). Following treatment with indomethacin, PGE₂ and calcium fell to normal levels in three patients (breast, colon, renal carcinomas). These results suggest: (1) A bimodal distribution of PGEs exists in hypercalcemic cancer patients. (2) There was some evidence of lack of whole molecule iPTH suppression in these patients. (3) Multiple stimuli of calcium mobilization may play an important etiologic role in a few hyercalcemic cancer patients and may explain the failure of indomethacin to control serum Ca⁺⁺ in some patients with elevated PGE₂.