Pathogenesis of hypercalcemia in lymphosarcoma cell leukemia. Role of an osteoclast activating factor-like substance and a mechanism of action for glucocorticoid therapy.
The pathogenesis of hypercalcemia and mode of action of glucocorticoid therapy was examined in a patient with lymphosarcoma cell leukemia. Circulating neoplastic cells were cultured in vitro and secreted a bone-resorbing factor. The bone-resorbing factor was partially purified with the use of a bioassay for bone resorption, and was found to be chromatographically and pharmacologically similar to osteoclast activiating factor (OAF), which is produced by normal mitogen-activated peripheral blood lymphocytes. Other factors which stimulate bone resorption, such as parathyroid hormone, prostaglandins and the vitamin D metabolites, were excluded by criteria which included dose-response curves, radioimmunoassays, extraction in organic solvents and failure of glucocorticoids to inhibit bone-resorbing activity. The patient's hypercalcemia responded rapidly to prednisone therapy. The effects of the bone-resorbing factor secreted by the neoplastic cells on bone cultures to which cortisol was added were examined. Cortisol inhibited bone resorption directly at low doses (10(-8) M), which suggests that prednisone may have lowered the serum calcium in this patient by direct inhibition of bone resorption.
D000368:Aged; D001862:Bone Resorption / Q000187:drug effects; D002478:Cells, Cultured; D002850:Chromatography, Gel; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D006934:Hypercalcemia / Q000097:blood / Q000209:etiology*; D007938:Leukemia / Q000097:blood / Q000150:complications* / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D010010:Osteoclasts; D010281:Parathyroid Hormone / Q000378:metabolism
D010281:Parathyroid Hormone; D006854:Hydrocortisone