Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypercalcemia in patients with breast cancer is usually attributed to osteolytic bone metastases. Seventeen patients with biopsy-proved breast cancer and hypercalcemia were identified in a prospective, unselected manner. Biochemical and clinical evaluation included measurements of parathyroid hormone, nephrogenous cAMP, vitamin D metabolites, fasting calcium excretion, and maximal tubular phosphate reabsorption, and bone radionuclide scanning. Tumor histologic findings were also reviewed. Four of the 17 patients (23.5 percent) had no evidence of bone involvement by bone scanning or radiography. Two additional patients (a total of 35 percent) appeared to have a humoral component to their hypercalcemia as determined by the presence of elevated nephrogenous cAMP excretion. These observations suggest that humoral, tumor-derived products may play a more important role in the hypercalcemia of breast cancer than has been previously recognized.
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PMID:Hypercalcemia in breast cancer. Reassessment of the mechanism. 303 97

The effects of a small dose of calcitriol (less than or equal to 0.50 micrograms/day) on parathyroid and renal function, bone histomorphometry, and aluminum (Al) metabolism were studied in a randomized double blind study of 30 patients with predialysis chronic renal failure. The patients were followed at least monthly for 8 months. Serum Al levels were measured, and transiliac bone biopsies, double labeled with tetracycline, were obtained at both the beginning and end of the 8-month treatment period. Serum calcium and ionized calcium concentrations increased in the treatment group, and the calcitriol dosage had to be reduced in 8 patients at least once because of hypercalcemia. Calcitriol treatment did not significantly influence either serum A1 levels or the presence of stainable Al in bone. Serum PTH, urinary cAMP excretion, and bone resorption indices decreased in the treatment group, indicating suppression of parathyroid hyperfunction. Throughout the study renal function decreased at a similar rate in both groups, suggesting that calcitriol treatment had no depressive effect on renal function. We conclude that a low dose of calcitriol may be used to preserve or even restore bone metabolism in patients with predialysis chronic renal failure if serum calcium is closely followed and hypercalcemia promptly treated.
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PMID:Low dose calcitriol versus placebo in patients with predialysis chronic renal failure. 318 64

Administration of the antifungal drug ketoconazole reduces serum 1,25-dihydroxyvitamin D (1,25-D) levels in normal subjects. To determine whether a similar effect occurs in hypercalcemic patients, ketoconazole (200 mg every 8 h for 7 days) was given to nine patients with confirmed primary hyperparathyroidism, three patients with probable primary hyperparathyroidism who were awaiting surgery, and three patients with mild hypercalcemia of uncertain etiology who were being followed. Ketoconazole administration led to a significant reduction in mean serum 1,25-D levels in the hypercalcemic patients [basal, 64 +/- 7 (+/- SEM) pg/mL (154 +/- 17 pmol/L) vs. 36 +/- 5 pg/mL (86 +/- 12 pmol/L) after ketoconazole; P less than 0.001]. Serum total calcium fell slightly but significantly [basal, 11.05 +/- 0.17 mg/dL (2.76 +/- 0.04 mmol/L) vs. 10.77 +/- 0.16 (2.69 +/- 0.04 mmol/L) after ketoconazole; P less than 0.02], but the falls in total serum calcium and serum 1,25-D after ketoconazole treatment were not correlated with one another. Ketoconazole administration did not alter serum ionized calcium, 25-hydroxyvitamin D, phosphate, alkaline phosphatase, or PTH concentrations or urinary cAMP excretion. The responses to ketoconazole were similar in all three patient subgroups. We conclude that short term administration of ketoconazole to hypercalcemic patients causes a substantial fall in serum 1,25-D and a small fall in total serum calcium. These effects render ketoconazole a potentially useful agent for investigation of the importance of 1,25-D in patients with hypercalcemic disorders and for their treatment.
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PMID:Ketoconazole-induced reduction in serum 1,25-dihydroxyvitamin D and total serum calcium in hypercalcemic patients. 336 Sep 1

A variety of solid tumors secrete proteins that are immunochemically distinct from parathyroid hormone (PTH) but activate PTH-responsive adenylate cyclase. Such PTH-like proteins have been proposed as mediators of the hypercalcemia and hypophosphatemia frequently associated with malignancies. We purified to apparent homogeneity a PTH-like protein with a molecular weight of 6,000, that is produced by human renal carcinoma cells. The amino-terminal sequence of the PTH-like protein and that of human PTH were found to display at least five identities in the first 13 positions. The purified protein bound to PTH receptors, activated adenylate cyclase in renal plasma membranes, and stimulated cAMP formation in rat osteosarcoma cells. The PTH-like protein reproduced two additional effects of PTH, stimulation of bone resorption in fetal rat limb bone cultures and inhibition of phosphate uptake in cultured opossum kidney cells. These properties are consistent with a role for PTH-like proteins as mediators of the syndrome of malignancy-associated hypercalcemia.
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PMID:Parathyroid hormonelike protein from human renal carcinoma cells. Structural and functional homology with parathyroid hormone. 368 May 30

Peptides corresponding to the amino-terminal region of the parathyroid hormone-related protein (PTHrP) of humoral hypercalcemia of malignancy were synthesized. A 34-amino acid peptide, PTHrP(1-34), was two to four times more potent than bovine or human PTH(1-34) in bioassays promoting the formation of adenosine 3',5'-monophosphate (cAMP) and plasminogen activator activity in osteogenic sarcoma cells and adenylate cyclase activity in chick kidney membranes. Like parathyroid hormone itself, in which the activity resides in the first 34 residues, PTHrP peptides of less than 30 residues from the amino terminus showed substantially reduced activity. PTHrP(1-34) had only 6% of the potency of bovine PTH(1-34) in promoting bone resorption in vitro. PTHrP(1-34) strongly promoted the excretion of cAMP and phosphorus and reduced the excretion of calcium in the isolated, perfused rat kidney consistent with the symptoms seen in malignant hypercalcemia.
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PMID:Parathyroid hormone-related protein of malignancy: active synthetic fragments. 368 95

The Leydig cell tumor Rice H-500 is a model of humoral hypercalcemia of malignancy. Hypercalcemia is considered to result mainly from increased bone resorption. However, a change in renal tubular reabsorption of calcium (Ca) as a contributing factor to the hypercalcemia has not yet been recognized. The purpose of this study was to examine whether the renal handling of Ca was altered in Leydig cell tumor-bearing rats. To avoid counterregulations by Ca-regulating hormones, the effect of the Leydig cell tumor on plasma Ca and phosphate (Pi), urinary Ca and Pi excretion, as well as Ca and Pi renal tubular reabsorptive capacity was investigated in thyroparathyroidectomized rats. Clearance experiments were conducted at a time of tumor development when the glomerular filtration rate was not compromised. Under these conditions, tubular reabsorption of Ca was stimulated, and the maximal tubular reabsorption of Pi was markedly reduced (2.69 +/- 0.27 vs. 4.57 +/- 0.21 mumol/min; P less than 0.001). These changes were accompanied by increased urinary cAMP excretion (77.1 +/- 6.3 vs. 34.7 +/- 2.8 pmol/ml glomerular filtrate; P less than 0.001). These results indicate that the Leydig cell tumor produces a factor with PTH-like activity on the renal tubular reabsorption of Ca and Pi. The increased tubular reabsorption of Ca may play an important role in the pathogenesis of Leydig cell tumor-induced hypercalcemia. This animal model appears to be particularly appropriate for studying the mechanisms of certain types of humoral hypercalcemia of malignancy, as some cancer patients display a change in the renal handling of Ca similar to that observed in primary hyperparathyroidism.
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PMID:Parathyroid hormone-like changes in renal calcium and phosphate reabsorption induced by Leydig cell tumor in thyroparathyroidectomized rats. 375 93

Sarcoidosis is frequently attended by hypercalciuria and sometimes by hypercalcaemia. The type of hypercalciuria and its relationships with disease extension and activity have rarely been investigated. In order to clarify these issues we undertook an investigation by a calcium absorption test in 39 patients with untreated thoracic sarcoidosis, and tried to establish correlations with vitamin D3 metabolism and some features of the disease. We found three types of responses. Group I (n = 12) with a normal test had normal 1,25-(OH)2D3 and rare extrathoracic localisations. Group II (n = 14) with absorptive hypercalciuria had higher serum calcium; 1,25-(OH)2D3 (p less than 0.001) and the free 1,25-(OH)2D3 index (p less than 0.05) were raised. Sarcoidosis was more often inflammatory, developing and disseminated. Group III (n = 13) had resorptive hypercalciuria, and hypercalcaemia was frequent. 1,25-(OH)2D3 (p less than 0.01) and the free 1,25-(OH)2D3 index (p less than 0.05) were raised but to the same degree as in Group II. Sarcoidosis was more disseminated and developing than in Groups I and II. In the 39 patients, iPTH and nephrogenous cAMP were low. Post-calcium load urinary calcium/creatinine (Ca/Cr) and 1,25-(OH)2D3 were correlated (p less than 0.05). Extrathoracic extension was associated with higher fasting urinary Ca/Cr (p less than 0.001), and development with higher post-load urinary Ca/Cr (p less than 0.001). Thus, absorptive hypercalciuria is related to the development of sarcoidosis and can be explained by high free 1,25-(OH)2D3, while resorptive hypercalciuria seems to be linked with disease extension. In such a case, the mechanism of osteolysis is not solely accounted for by high 1,25(OH)2 vitamin D3 serum levels, and we postulate that some other factor is at work, related to the extent of the granulomatous process.
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PMID:Resorptive versus absorptive hypercalciuria in sarcoidosis: correlations with 25-hydroxy vitamin D3 and 1,25-dihydroxy vitamin D3 and parameters of disease activity. 383 15

We have studied a hypercalcemic patient with sarcoidosis and advanced renal failure. Bone biopsy and urinary cAMP excretion indicated suppression of parathyroid function. 1,25(OH)2D levels were moderately elevated and dropped to low normal levels during prednisolone treatment. Discontinuation of prednisolone treatment caused deterioration of renal function and hypercalcemia, 1,25(OH)2D serum levels being within the normal range. Our data demonstrate the rapid speed at which prednisolone causes a drop in serum 1,25(OH)2D level. Since hypercalcemia was observed both during periods of hypercalciuria and normal serum 1,25(OH)2D levels, increased sensitivity to active vitamin D seems likely. There was no significant correlation between 25(OH)D, 24,25(OH)2D or 25,26(OH)2D. Furthermore there was no correlation between any of these three metabolites and either 1,25(OH)2D or serum calcium.
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PMID:Rapid effect of prednisolone on serum 1,25-dihydroxycholecalciferol levels in hypercalcemic sarcoidosis. 384 60

2 patients with chronic myelogenous leukaemia developed hypercalcaemia and severe myelofibrosis in the terminal phases of their disease. Hormonal studies excluded the hypercalcaemia being caused by primary hyperparathyroidism or ectopic parathyroid hormone secretion. Its development was unrelated to the phenotype of the blast cells, as assessed by conventional cytochemistry and immunological surface typing. The finding of increased urinary cAMP excretion in 1 of the patients suggests a circulating, nonparathyroid humoral bone resorbing factor with partial biological PTH-activity to be one of the pathogenetic mechanisms responsible for the occurrence of hypercalcaemia in patients with chronic myelogenous leukaemia.
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PMID:Hypercalcaemia in the accelerated phase of chronic myelogenous leukaemia: no relationship to the phenotype of the blast cells. 386 33

Three patients with hypercalcemia associated with malignant lymphoma and elevations in plasma 1,25-dihydroxyvitamin D [1,25-(OH)2D] are described. In addition to the elevation of circulating 1,25-(OH)2D, these three patients were characterized by suppressed immunoreactive PTH levels and urinary cAMP excretion, elevated fasting urinary excretion of calcium, and absence of adenylate cyclase-stimulating activity in the tumor extracts. Bone marrow biopsy and skeletal radionuclide scans were negative for lymphoma in two patients. Surgical excision of a solitary splenic lymphoma in one patient and medical therapy in another patient resulted in rapid normalization of the serum calcium and plasma 1,25-(OH)2D levels. These findings confirm an earlier observation that elevated plasma levels of 1,25-(OH)2D may occur in certain patients with lymphoma and suggest that this vitamin D metabolite may act as a humoral or systemic mediator of hypercalcemia. Proof that this is the case and identification of the source of 1,25-(OH)2D production will require further study.
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PMID:Elevations in circulating 1,25-dihydroxyvitamin D in three patients with lymphoma-associated hypercalcemia. 387 Oct 92


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