15-keto-13-14-dihydroprostaglandin-e2 and Hypercalcemia

Dogs with lymphosarcoma and hypercalcemia had decreased trabecular bone volume and increased osteoclastic osteolysis, whereas dogs with lymphosarcoma that were normocalcemic did not have increased bone resorption. Increased osteoclastic resorption was present only in bone from hypercalcemic dogs that contained neoplastic tissue but not in bone free of tumors, suggesting that the factor(s) responsible for stimulating bone resorption were elaborated locally by the tumor tissue. Hypercalcemic dogs with lymphosarcoma had decreased concentrations of plasma immunoreactive parathyroid hormone and serum 1,25-(OH)2D compared with normocalcemic dogs with lymphosarcoma and control dogs with and without other neoplasms. Immunoreactive parathyroid hormone was not detected in lymphosarcoma tissue. The plasma concentration of 13,14-dihydro-15-keto-prostaglandin E2 (PGE2M) was increased approximately 2-fold in hypercalcemic dogs with lymphosarcoma as compared with other groups. Urine excretion of calcium, phosphorus, and hydroxyproline were increased in hypercalcemic dogs with lymphosarcoma. Ultrastructurally, lymphosarcomas were composed of tumor cells with large nuclei and a paucity of cytoplasmic organelles. Light and electron microscopic examination of parathyroid glands revealed inactive or atrophic chief cells in dogs with lymphosarcoma and hypercalcemia. The increased osteoclastic bone resorption in hypercalcemic dogs with lymphosarcoma was not mediated by increased circulating levels of immunoreactive parathyroid hormone and 1,25-(OH)2D but was dependent upon infiltration of bone marrow by neoplastic cells and, presumably, the local production of a bone resorption-stimulating factor.

Topics: Animals; Bone and Bones; Calcitriol; Cyclic AMP; Dinoprostone; Dogs; Hydroxyproline; Hypercalcemia; Lymphoma, Non-Hodgkin; Microscopy, Electron; Parathyroid Glands; Parathyroid Hormone; Prostaglandins E

The etiology of tumor-induced hypercalcemia was investigated in a transplantable Leydig cell tumor of the Fischer rat. In this model, serum calcium rose from a baseline of 10.4 +/0 0.3 mg/dl to 12.5 + 0.4 mg/dl at day 10 and 16.4 +/- 1.3 mg/dl (p less than 0.001) at day 13 post transplant. Urinary calcium also increased from 1.52 +/- 0.17 mg/d to 3.52 + 0.72 mg/d (Day 12, p less than 0.01). Serum phosphate decreased from a baseline of 7.5 +/- 0.3 mg/dl to 5.5 +/- 0.6 mg/dl at day 13 (p less than 0.05). At day 13 serum immunoreactive parathyroid hormone levels fell 76% from baseline (p less than 0.01). Calcitonin increased from 59 +/- 2 pg/ml to 88 +/- 9 pg/ml (p less than 0.02). The plasma prostaglandin E metabolite, 13,14-dihydro-15-keto-PGE2 increased from 407 +/- 103 pg/ml to 647 +/-62 pg/ml (p less than 0.05) and the active Vit D compound 1,25(OH)2D increased from 94.8 +/- 5.2 pg/ml to 162.3 +/- 11.8 pg/ml (p less than 0.01). Urinary cyclic AMP did not decrease in parallel with the parathyroid hormone level and, in fact, increased from 146 +/- 3 nmol/d to 172 +/- 27 nmol/d (NS). Administration of the cyclooxygenase inhibitor indomethacin (20 mg/Kg/d) or hydrocortisone (50 mg/Kg/d) did not prevent the development of hypercalcemia. This model is similar to many patients with humoral hypercalcemia of malignancy who demonstrate suppression of parathyroid hormone with elevated urinary cyclic AMP excretion and may prove useful in the understanding of the responsible mechanisms.

Topics: Animals; Calcitriol; Calcium; Cyclic AMP; Dinoprostone; Disease Models, Animal; Hypercalcemia; Leydig Cell Tumor; Male; Neoplasm Transplantation; Parathyroid Hormone; Phosphates; Prostaglandins E; Rats; Rats, Inbred F344; Testicular Neoplasms

A women with hypercalcemia and a hypernephroma confined to the left kidney underwent nephrectomy and subsequent resolution of hypercalcemia. Serum parathyroid hormone was undetectable in peripheral blood as well as in the left renal vein at surgery. Parathyroid hormone was also undetectable in the tumor extract using three different antisera to parathyroid hormone. Measurement of plasma prostaglandin E and 13, 14-dihydro-15-keto-prostaglandin E2 revealed levels within the normal range. The serum 1,25-dihydroxyvitamin D concentration was below normal and nephrogenous cyclic adenosine monophosphate was markedly elevated. The humoral agent responsible for hypercalcemia in this patient was not identified. This case emphasizes the need to search for new hypercalcemic factors in patients with hypercalcemia of malignancy.

Topics: Adenocarcinoma; Adult; Calcitriol; Cyclic AMP; Dinoprostone; Female; Furosemide; Humans; Hypercalcemia; Kidney Neoplasms; Parathyroid Hormone; Phosphorus; Prostaglandins E

The relationship between plasma levels of 15-keto-13, 14-dihydroprostaglandin E2 (15K-H2-PGE2) and serum calcium levels was studied in nontumor-bearing rabbits and in rabbits bearing the VX2 carcinoma intramuscularly and intra-abdominally. The plasma levels of 15K-H2-PGE2 in the two groups of tumor-bearing animals did not vary significantly but was several fold greater than in nontumor-bearing rabbits. Rabbits bearing the VS2 carcinoma intramuscularly developed hypercalcemia between the second and third week after implantation of neoplastic tissue and remained hypercalcemic until they expired. The serum calcium levels in rabbits bearing the VX2 carcinoma intra-abdominally did not vary significantly from those of nontumor-bearing rabbits. The differences in the serum calcium levels in rabbits bearing the VX2 carcinoma at intramuscular and intra-abdominal implant sites may be related to different extents of metabolism by the lung and by the liver of prostaglandin E2 or other cyclooxygense of polyenoic fatty acids produced by the tumor.

Topics: Animals; Calcium; Creatine; Dinoprostone; Hypercalcemia; Muscles; Neoplasm Transplantation; Neoplasms, Experimental; Peritoneal Cavity; Prostaglandins E; Rabbits