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

Increased bone resorption (BR) and increased renal tubular reabsorption of calcium (TRCa) may both be involved in the pathogenesis of hypercalcemia of malignancy (HM). We have evaluated the relative importance of these two mechanisms in 33 patients with HM after extracellular volume expansion and after single infusion of clodronate (C12MDP: 500 mg iv over 8 h). The fasting urine Ca/creatinine ratio was taken as an index of BR (BRI). An index of TRCa was calculated (TRCaI) from a nomogram based on the relationship between urine Ca excretion per unit of glomerular filtration rate and plasma Ca (PCa). Mean (+/- SEM) PCa fell from 3.29 +/- 0.07 to 2.69 +/- 0.05 mmol/l three days after C12MDP (n = 33, p less than 0.001), a response similar to that obtained with repeated daily iv injections of 500 to 1000 mg C12MDP. The pathogenesis of hypercalcemia varied according to the type of neoplasm. BRI was the highest in multiple myeloma and breast tumors. TRCaI was markedly increased in squamous-cells lung, bladder, kidney and liver carcinomas, reaching levels observed in primary hyperparathyroidism. TRCaI was normal in most cases of multiple myeloma. Breast tumors appeared to be heterogeneous with respect to TRCaI. The fall in PCa in response to a single infusion of C12MDP was usually most marked in cancer patients with elevated BRI and normal TRCaI. It was very modest in patients with high TRCaI and slightly elevated BRI. In conclusion, this study confirms that stimulation of bone resorption is not the only mechanism of the maintenance of hypercalcemia of malignancy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bone and renal components in hypercalcemia of malignancy and responses to a single infusion of clodronate. 297 82

The pathogenic mechanisms causing malignant hypercalcaemia are primarily increased bone calcium mobilisation and renal calcium retention. In some reticuloendothelial malignancies, enhanced intestinal calcium absorption may also play a role. Malignant hypercalcaemia is a life-threatening condition, and there are many patients with malignancy in whom suppression of this complication is most desirable. In such cases, successful management of the hypercalcaemia will enable the overall treatment aims, such as tumour removal or ablation, to be achieved. Acute treatment involves the rapid lowering of serum calcium from potentially fatal concentrations, and comprises the use of intravenous rehydration, calcitonin and diphosphonates. In the longer term, other measures may be introduced to maintain and control the calcium concentration while specific antitumour therapy is instituted.
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PMID:Current management of malignant hypercalcaemia. 305 27

The three biologic activities most commonly associated with tumors that produce Humoral Hypercalcemia of Malignancy (HHM) include; 1) adenylate cyclase stimulating activity (PTH-like activity), 2) in vitro bone resorbing activity, and 3) transforming growth factor activity. The canine adenocarcinoma (CAC-8) model of HHM contains all three activities and the first two are inhibited by a PTH receptor antagonist. These data in light of the recent purification of PTH-related peptides from human tumors suggest that CAC-8 produces a PTH-related protein that is important in the pathogenesis of hypercalcemia. The CAC-8 tumor is a well characterized example of HHM and offers several advantages for further investigations on the pathogenesis of HHM: 1) transplantable tumor line from a spontaneous neoplasm in the dog, 2) tumor extracts contain the three biologic activities associated with HHM, 3) slow progressive growth rate in nude mice permits investigations on treatment of HHM, 4) increased bone resorption and formation in nude mice mimics the effects of PTH on bone, and 5) the only model of HHM that has been demonstrated to contain bone resorbing activity that can be inhibited by a PTH receptor antagonist.
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PMID:Pathogenesis of humoral hypercalcemia of malignancy. 306 80

Many factors, such as interleukin 1, transforming growth factor alpha, tumour necrosis factor alpha and beta, and prostaglandins, have been implicated in the pathogenesis of the humoral hypercalcaemia of malignancy (Mundy and Martin, 1982; Martin and Mundy, 1987; Mundy et al, 1984). Much interest in the past has also centred upon the likelihood of ectopic secretion of PTH in this condition. We have purified a protein (PTHrP) implicated in HHM from a human lung cancer cell line (BEN). Full-length cDNA clones have been isolated and found to encode a pre-pro-peptide of 36 amino acids and a mature protein of 141 amino acids. Eight of the first 13 amino acids were identical with human PTH, although antisera directed to the aminoterminus of PTHrP do not recognize PTH; this homology is not maintained in the remainder of the molecule. PTHrP therefore represents a previously unrecognized hormone, possibly related to the PTH gene by a gene duplication mechanism. In support of this notion, the PTHrP gene has been localized to the short arm of chromosome 12; it is believed that chromosome 11, containing the PTH gene, and chromosome 12 are evolutionarily related. In addition, the human PTHrP gene has been isolated, characterized, and shown to have an intron-exon arrangement that is more complex than the PTH gene. It is possible that the original ancestral gene is indeed the PTHrP gene; resolution of this question awaits studies in lower species. Peptides synthesized to the predicted protein sequence have allowed detailed structure-function studies that have identified aminoterminal sequences to be responsible for the biological effects of the molecule. Antibodies raised against the various synthetic peptides have led to the immunohistochemical localization of PTHrP in many human squamous cell carcinomas as well as in a subpopulation of keratinocytes of normal skin. The availability of these antibodies has opened the way for the development of a radioimmunoassay to detect PTHrP in the sera of cancer patients at risk of developing hypercalcaemia. The recent characterization of PTHrP-like activity in the ovine fetus suggests some physiological function for PTHrP. It is possible that PTHrP, as the fetal counterpart of PTH, has the role of maintaining the maternal-fetal calcium gradient. The isolation and characterization of PTHrP has added to our understanding of the mechanisms of hypercalcaemia and may contribute to the understanding of other metabolic bone diseases, such as osteoporosis and Paget's disease. Finally, and perhaps most importantly, PTHrP may play a hitherto unrecognized role in normal cell physiology.
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PMID:Parathyroid hormone-related protein: a novel gene product. 307 45

To evaluate the efficacy of intravenous etidronate disodium (etidronate) in controlling hypercalcemia of malignancy, 20 patients with known malignant disease and hypercalcemia were randomly assigned on a two-to-one basis to receive etidronate, 7.5 mg/kg of body weight, or placebo for three to five days. All patients received 3,000 ml of saline and 40 mg of furosemide per day. Eighteen patients completed the study. Eleven of 12 patients (92 percent) in the etidronate group attained normocalcemia, compared with two of six (33 percent) in the placebo group (p = 0.05). The etidronate group showed a greater decrease in the serum calcium level than did the placebo group (p less than 0.02). Renal calcium excretion decreased significantly in the etidronate group but not in the placebo group. Intravenous etidronate in combination with rehydration and furosemide constitutes a safe and effective alternative in the treatment of hypercalcemia of malignancy.
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PMID:Etidronate disodium in the management of malignancy-related hypercalcemia. 310 36

The present studies examined renal calcium (Ca) clearance in an animal model of malignancy-associated humoral hypercalcemia (MAHH) (a human squamous cell lung carcinoma carried in athymic mice). Three groups of animals--controls, normocalcemic tumor-bearing animals and hypercalcemic tumor-bearing animals--were studied in the basal state and during Ca infusion. Baseline Ca clearance was slightly but significantly elevated in the tumor-bearing hypercalcemic animals compared with the other two groups of animals. This clearance value was, however, inappropriately low for the serum Ca value. In the control and in the normocalcemic tumor-bearing animals, Ca clearance increased markedly during Ca infusion. This increase in renal Ca clearance was markedly blunted in the hypercalcemic animals compared with both the controls and the normocalcemic tumor-bearing animals. We conclude that increased renal Ca resorption contributes significantly to the pathogenesis of hypercalcemia of malignancy.
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PMID:Increased renal calcium reabsorption in an animal model of hypercalcemia of human malignancy. 319 67

The efficacy of intravenous aminohydroxypropylidene bisphosphonate as treatment for the hypercalcemia of malignancy was examined in a phase II multicenter study in 132 patients with a large variety of primary tumors. This provided an opportunity for an analysis of the separate influences of bone resorption and renal calcium handling on the genesis and maintenance of hypercalcemia. The results demonstrated that increased bone resorption is the major contributory factor and that inhibition with bisphosphonate normalizes the serum calcium concentration within five days in more than 90 percent of patients. Hypercalcemia is sustained by an inability of the kidney to deal efficiently with a chronically increased calcium load. This is influenced by the requirements of volume regulation in the presence of a sodium diuretic effect of hypercalcemia and is very sensitive to induced variations of sodium load. In addition, in a minority of patients, direct renal actions of tumor-derived humoral factors adversely reduce the ability to excrete calcium. For optimal treatment of tumor-induced hypercalcemia, bisphosphonate treatment should be combined with intravenous administration of saline solution.
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PMID:Role of bone and kidney in tumor-induced hypercalcemia and its treatment with bisphosphonate and sodium chloride. 330 Mar 3

The treatment of hypercalcemia of malignancy is troublesome. Personal experience with breast cancer associated hypercalcemia is presented. Eight patients were hydrated with intravenous administration of saline solution containing high doses of salmon calcitonin and subsequently six were treated with antiblastic polychemotherapy. Calcium level fell to normal in all patients. Hypercalcemia, with or without evidence of metastatic bone disease, may be caused by the production of humoral substance by tumoral tissue. In our experience the first therapeutic stage is the infusion of saline solution containing high doses of calcitonin, while the elective treatment is antiblastic polychemotherapy which, acting on tumour growth, may inhibit the release of humoral mediators of hypercalcemia causing a slower but stable reduction in serum calcium level.
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PMID:[Update on paraneoplastic hypercalcemia. Our experience in the treatment of hypercalcemic states of patients with advanced breast carcinoma]. 340 54

Following rehydration with intravenous saline, 27 patients with hypercalcemia of malignancy were treated with a total of 32 courses of 3-amino-1-hydroxypropylidene-1, 1-bisphosphonate (APD) given by slow intravenous infusion. Twelve treatments consisted of daily infusions of APD for between two and six days whereas single-dose APD was used in 20 treatments. Mean albumin-adjusted serum calcium fell to the upper end of the reference range at seven days from the start of treatment, both in multiple-dose and in single-dose treatment groups. No relationship between total dose of APD and hypocalcemic response was observed. However, second treatments with APD following recurrence of hypercalcemia in five patients were significantly less effective than the original therapy, suggesting that resistance to APD may develop. Multiple-dose and single-dose intravenous APD treatments appear to be equally effective in the acute management of hypercalcemia of malignancy.
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PMID:A comparison of single and multiple intravenous infusions of 3-amino-1-hydroxypropylidene-1, 1-bisphosphonate (APD) in the treatment of hypercalcemia of malignancy. 343 16

Humoral hypercalcemia of malignancy is a common paraneoplastic syndrome which is characterized by hypercalcemia resulting from secretion by tumors of a circulating bone-resorbing factor. Evidence suggests that in many instances this factor is an adenylate cyclase-stimulating protein which shares features with, but is distinct from, parathyroid hormone (PTH). The current report describes the purification to homogeneity from a humoral hypercalcemia of malignancy-associated tumor of a novel, basic, highly potent PTH-like adenylate cyclase-stimulating protein. This factor differs from previously described PTH-like factors with respect to size, amino acid composition, and specific activity.
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PMID:Identification of a novel 17,000-dalton parathyroid hormone-like adenylate cyclase-stimulating protein from a tumor associated with humoral hypercalcemia of malignancy. 358 10


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