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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There are a variety of water and electrolyte disorders in patients with cancer. These disorders occur during the growth of tumors, generally as a consequence of inadequate intake and absorption of electrolytes, renal failure secondary to tumor or rapid tumor destruction and production of metabolically active substances by the tumor. In this paper, the electrolyte abnormalities associated with cancer were reviewed. Hyponatremia is one of the most common clinical electrolyte abnormalities in advanced cancer. Some patients may have hyponatremia, in spite of increased total body sodium and absence of a defect in water diuresis. This status is designated as "sick cell syndrome" or "essential hyponatremia". In addition, the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in association with various tumors has been described. This syndrome is principally due to water retention, but can also be due to continuous urinary loss of sodium, and hypo-osmolality. Hypercalcemia is associated with coexistent primary hyperparathyroidism, prostaglandin (PGE2) or osteoclast-activating factor. It now seems likely that ectopic PTH is rarely the cause of hypercalcemia in nonparathyroid cancer. There are no data supporting the ectopic production of vitamin D-like substance as an important factor in the hypercalcemia of cancer. There are three general categories in which patients with hypercalcemia and cancer may be placed: those with bone metastases, those without bone metastases of solid tumors and those with hematologic malignancies. Hypokalemia is associated with ectopic ACTH- and insulin--producing tumors, and is often found in patients with mucin-secreting, potassium-losing adenocarcinoma of the colon.
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PMID:[Electrolyte abnormalities associated with cancer: a review]. 352 93

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.
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PMID:Hypercalcemia in association with a Leydig cell tumor in the rat: a model for tumor-induced hypercalcemia in man. 628 3

In prepuberal female rats with acute bilateral nephrectomy or chronic subtotal nephrectomy, the increase of ovarian cAMP concentration in response to submaximal doses of luteinizing hormone (LH 10 micrograms) and human chorionic gonadotropine (hCG 2.5 IU) was diminished (CO + 2.5 IU hCG 488 +/- 49 pmoles cAMP/mg protein; NX + 2.5 IU hCG 366 +/- 56. P less than 0.05). The cAMP response to follicle stimulating hormone (FSH) was unchanged. The abnormality was found both after administration of LH in vivo and incubation of ovaries with LH in vitro. Similarly, plasma estradiol concentrations in response to submaximal hCG stimulation were diminished. Basal cAMP concentrations and cAMP concentrations after maximal stimulation were unchanged. The defect was observed both in ovaries of untreated prepuberal rats, of pregnant mare serum (PMS)-treated rats (follicular phase) and PMS/hCG-treated rats (luteal phase). Diminished ovarian cAMP response to LH was observed both in parathyroid intact and in parathyroidectomized rats. Administration of 1,25(OH)2D3 in physiological doses (60 ng/kg) to acutely uremic rats restored diminished ovarian cAMP response to submaximal LH stimulation irrespective of parathyroid status. The effect of 1,25(OH)2D3 could not be reproduced by hypercalcemia resulting from intraperitoneal calcium injection. In vivo administration of indomethacin further diminished ovarian cAMP response in uremic animals and had no effect in control animals. Incubation of ovaries with PGE1 and PGE2 increased basal and stimulated cAMP concentrations and abolished the difference between control and uremic animals. The diminished response of ovarian cAMP content to submaximal doses of hCG was not corrected by bromocriptine (1 mg/kg) despite normalization of hyperprolactinemia. The present study shows diminished ovarian cAMP and plasma estradiol response to LH in experimental uremia. It documents a role of 1,25(OH)2D3 and prostaglandins in the genesis of this abnormality.
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PMID:Diminished response of ovarian cAMP to luteinizing hormone in experimental uremia. 629 98

A case of humoral non-parathyroid hypercalcemia in a breast cancer patient is discussed. Bone metastases developed 23 months after the first clinical evidence of increased serum calcium levels and did not appear to be etiologically involved in this case of hypercalcemia. Serum levels of I-PTH and PGE2 were normal, as were urinary c-AMP levels. Furthermore, no significant response to corticosteroid therapy was observed. However, the correlation between the activity of metastatic disease and calcemia suggests that this cancer produced humoral factor(s) with calcium-mobilizing activity.
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PMID:Humoral nonparathyroid hypercalcemia without evidence of bone involvement. 630 87

PGE2 overproduction by a nephroblastoma associated with hypercalcemia was clearly demonstrated in a 2-month-old girl. Compared with normal tissue, tumor showed greater phospholipase A2 and PGE2 synthetase activities but metabolized PGE2 at a faster rate. Of the enzymes involved in PGE2 synthesis, those which transform arachidonic acid into PGE2 seem to be more active.
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PMID:Synthesis and catabolism of PGE2 by a nephroblastoma associated with hypercalcemia without bone metastases. 633 25

Immunoreactive PGE2 was determined in 11 surgically removed malignant tumors. When compared to adjacent non-malignant tissues PGE2 content was significantly higher in the neoplastic tissues. These findings support the view that PG may play a role in cell proliferation and/or vascular supply to tumor tissues. The hypothesis was also discussed that PGE2 may represent a tumor against host defense since it can decrease spontaneous and antibody dependent cytotoxicity. PGE2 may also play a role in tumor induced osteoporosis and hypercalcemia. If this hypothesis is correct PGE2 synthesis inhibitors may be employed as auxiliary antitumor agents.
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PMID:Prostaglandin E2 production by human tumors. Defense mechanism against the host? A preliminary report. 658 44

Cyclooxygenase products of arachidonic acid metabolism in the plasma of normal rabbits and animals bearing the VX2 carcinoma were separated by high performance liquid chromatography and the effluent fractions assayed by serologic methods. The products measured were 6-keto-PGF1 alpha, thromboxane B2, PGE2, PGF2 alpha, 13,14-dihydro-PGE2, 13,14-dihydro-15-keto-PGE2, 15-keto-PGE2, and 13,14-dihydro-15-keto-PGF2 alpha. In hypercalcemic, tumor-bearing rabbits, the plasma concentrations of 13,14-dihydro-15-keto-PGE2 and 13,14-dihydro-15-keto-PGF2 alpha were markedly elevated (in the range of 0.5 to 16 ng/ml). Previously unmeasured 6-keto-PGF1 alpha, thromboxane B2, 13,14-dihydro-PGE2 and 15-keto-PGE2 were not found in high concentrations in the plasma of tumor-bearing rabbits. These results add further support to our conclusion that the VX2 tumor produces hypercalcemia in the host by a mechanism which utilizes PGE2, rather than a subsequent metabolite of this prostaglandin, as the mediator between the neoplasm and bone.
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PMID:Analysis by high performance liquid chromatography of cyclooxygenase products of arachidonic acid metabolism in plasma of rabbits bearing the VX2 carcinoma. 677 79

Extracts of tumors from patients with humoral hypercalcemia of malignancy (HHM) were tested using an in vitro bone resorption assay in order to investigate the pathogenesis of the hypercalcemia. Bone resorption was assessed by comparing the percent release of previously incorporated 45Ca from paired halves of newborn mouse calvaria. Saline extracts of three out of five tumors from HHM patients caused a significant increase in 45Ca release relative to controls. Extracts of liver and non-HHM tumor did not cause significant resorption. Tumor-stimulated bone resorption was blocked by indomethacin and eicosatetraynoic acid, inhibitors of the synthesis of prostaglandins (PGs) and related metabolites of arachidonic acid, whereas resorption stimulated by parathyroid hormone (PTH), PGE2, or 1,25-(OH)2D3 was not. Furthermore, levels of immunoreactive PTH or PGE2 in tumor extracts were not sufficient to account for the degree of resorption observed. These observations indicate that PTH or PGE2 are not responsible for the bone resorption caused by extracts of tumors from these patients with HHM. Furthermore, they suggest that hypercalcemia in these patients may result from bone resorption stimulated by the local production in bone of PGs or related metabolites of arachidonic acid in response to a humoral factor elaborated by the tumor.
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PMID:Bone resorption and humoral hypercalcemia of malignancy: stimulation of bone resorption in vitro by tumor extracts is inhibited by prostaglandin synthesis inhibitors. 679 15

Hypercalcemias in lymphomas without bone involvement are exceptional. The mechanism of hypercalcemia, very rarely determined, results from release of parathyroid hormone like (PTH) or osteoclast activating factor like substances. Prostaglandins were not reported high in lymphomas with hypercalcemia. We report a case of hypercalcemia in large cell lymphoma with non-cleaved cell and without bone involvement. Plasma PGE2 were 775 pg/ml (normal 7,8 +/- 1,5 pg/ml), plasma PTH was 12 ng/prot./ml (normal 10-30 ng/prot./ml), calcemia was 3,7 mmol/l (normal 2,2-2,6 mmol/l). Ten days after the first chemotherapy, calcemia was normal, plasma PTH was undetectable and plasma PGE2 were 349 pg/ml. Nine months after the beginning of treatment, PGE2 were 16,8 pg/ml and calcemia 2,37 mmol/l. The possible roles of PGE2 in hypercalcemia and as tumor marker are discussed.
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PMID:[Hypercalcemia in large cell lymphoma. Possible role of prostaglandins E2 (author's transl)]. 695 69

Prostaglandin E levels were determined in the tumor and normal lung tissue in 14 normocalcemic patients with lung cancer. All of the tested extracts from tumor and normal lung tissue revealed the presence of prostaglandin E; the levels were significantly higher in tumor tissue as compared with normal lung tissue. All of the tested tissue culture media from the tumors and all but one of those tested from normal lung revealed the presence of prostaglandin E; the levels were significantly higher in tumor tissue as compared with normal lung. There was no correlation between the level of prostaglandin E production and subsequent development of hypercalcemia or bone metastases or the duration of survival. The studies suggest that production of prostaglandin E by the tumors is a common phenomenon even in normocalcemic patients, and therefore its presence in the tumor tissue from a hypercalcemic patient may not necessarily implicate prostaglandin E in the pathogenesis of hypercalcemia in that patient.
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PMID:Presence of prostaglandin E in lung tumors from normocalcemic patients. 708 Dec 72


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