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

The case of hypercalcemia secondary to metastasis to a benign parathyroid adenoma is reported. The patient had documented lung adenocarcinoma with multiple bone metastases and a mass in the lower anterior neck for at least 5 months before hypercalcemia and hypophosphatemia resistant to treatment developed. Autopsy revealed widespread metastatic disease including metastatic tumor invading a benign parathyroid adenoma. The analysis of four cases of metastatic cancer spread to a benign parathyroid adenoma reported previously revealed that two of them also had hypercalcemia during a late stage of the disease. There are data that the incidence of metastases to parathyroid gland might be as high as 11.9%, and the incidence of parathyroid adenomas in patients with cancer is significantly higher than in controls. The metastases to benign parathyroid adenomas might be another mechanism of hypercalcemia of malignancy.
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PMID:A case of adenocarcinoma of the lung associated with a neck mass and hypercalcemia. 191 81

It has been controversial whether increased renal tubular calcium reabsorption contributes to hypercalcemia in patients with malignancies. Moreover, whether this abnormality is associated with volume depletion, a parathyroid hormone-like effect, or other mechanisms has not been clarified. Eight consecutive patients with hypercalcemia due to a variety of tumor types were studied in detail. The glomerular filtration rate (iothalamate clearance) was reduced in all patients (0.98 +/- 0.10 (mean +/- SE) mL/s.1.73 m2; P less than 0.001) compared with normal controls (N = 9) (1.93 +/- 0.08 mL/s.1.73 m2), but it was similar to that in controls matched for renal insufficiency (N = 6) (1.15 +/- 0.05 mL/s.1.73 m2). During hypercalcemia produced by calcium infusion, urinary calcium excretion (millimoles of calcium per liter of glomerular filtrate) was increased in controls with renal insufficiency compared to those with normal renal function (P = 0.028). In all patients with hypercalcemia of malignancy, urinary calcium excretion was decreased compared with controls with renal insufficiency, but it was low in only five of eight patients compared with normal controls. Extracellular fluid volume (iothalamate volume of distribution) was not decreased in any patient, and urinary cAMP and/or plasma parathyroid hormone-like bioactivity were increased in six of eight patients. After treatment with an inhibitor of bone resorption, aminopropylidene 1,1 diphosphonate, abnormal renal calcium handling was not detected if the serum calcium normalized. It was concluded that increased renal tubular calcium reabsorption was consistently present in patients with hypercalcemia of malignancy compared with controls matched for renal insufficiency, but the proportion with the abnormality was underestimated if normal controls were used.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Altered renal calcium handling in hypercalcemia of malignancy. 195 31

We studied the effect of a single 5 mg intravenous infusion of amino-butylidene diphosphonate (ABDP) in nine patients with hypercalcemia of malignancy, in whom serum calcium values were stable or rising after intravascular volume expansion. Serum calcium fell progressively in all patients and in seven reached the normal reference range by day 6 (p less than 0.001). The decrease in serum calcium was associated with a decrease in the fasting urinary calcium/creatinine ratio (p less than 0.05). Hypercalcemia recurred in seven of the patients by day 12, but two patients remained normocalcemic for 21 days. We conclude that ABDP is a highly potent diphosphonate and that a single intravenous infusion is capable of inhibiting tumour-mediated bone resorption for several days.
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PMID:Effects of amino-butylidene diphosphonate in hypercalcemia due to malignancy. 205 31

The management of hypercalcemia of malignancy is guided by assessments of its various components. Since the intestine usually makes no contribution to hypercalcemia under these circumstances, the problem is to measure the net efflux of calcium out of bone and the ability of the kidneys to excrete the unwanted calcium load. Established relationships between serum and urinary calcium excretion rates allow the quantitation of the relative contribution of an impaired glomerular filtration rate, of reduced renal tubular calcium reabsorption, and of increased bone resorption. Since the renal handling of calcium is closely related to that of sodium in the proximal nephron, the rate of sodium excretion is an important variable in these measurements. A practical approach to the separation of hypercalcemia into its renal and skeletal components is described in this article. Examples of how these measurements can be used to assess the responses to various types of therapy for malignancy-associated hypercalcemia are also given.
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PMID:Assessment of renal and skeletal components of hypercalcemia. 210 28

Bisphosphonates (formerly diphosphonates), analogues of endogenous pyrophosphates, are potent inhibitors of osteoclastic bone resorption. While the exact mechanism of action remains poorly understood, etidronate, the only bisphosphonate currently available in the United States for the treatment of hypercalcemia, decreases the elevated serum calcium levels and alleviates the symptoms associated with hypercalcemia of malignancy. Both open and controlled clinical studies have demonstrated that this agent, administered at a dose of 7.5 mg/kg/d in 2-hour intravenous infusions over 3 to 7 days, promotes normocalcemia. In a randomized study, etidronate was shown to be superior to maximally approved doses of calcitonin. Moreover, when administered to patients without overt renal failure (serum creatinine less than 2.5 mg/dL), the drug is remarkably free of significant acute toxicity and side effects. Therefore, an important therapeutic aspect of this agent is that it permits concurrent antibiotic and chemotherapy administration. Judicious use of appropriate and specific pharmacologic intervention strategies in the patient with cancer-related hypercalcemia is expected to enhance quality of life, improve systemic cancer therapy tolerance, and reduce the morbidity of this serious neoplastic complication.
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PMID:Role of the bisphosphonate etidronate in the therapy of cancer-related hypercalcemia. 211 Mar 87

Of the many compounds belonging to the diphosphonate family, clodronate has been widely used in hypercalcemia and osteolysis of malignancy. All published reports indicate that clodronate can normalize plasma calcium in the majority of hypercalcemic, rehydrated cancer patients in whom increased bone resorption is the prevailing disturbed calcium flux. In these patients, clodronate, given intravenously either as a single infusion or as repeated daily administrations, can normalize serum calcium, usually 3-5 days after the onset of therapy. In these good responders, long-term maintenance treatment should be individually adjusted since relapse appears to depend upon the type of tumor, the extent of malignancy and the administration of anticancer therapy. In a subset of well-rehydrated hypercalcemic patients in whom increased tubular calcium reabsorption represents the prevailing disturbed calcium flux, the acute effect of clodronate on plasma calcium is incomplete, despite the normalization of bone resorption. This type of therapeutic response can be experimentally reproduced in diphosphonate-treated animals receiving a constant infusion of parathyroid hormone-related peptide, a peptide isolated from lung, kidney and breast carcinomas. This indicates that, in addition to antiosteolytic drugs, such as clodronate, patients with hypercalcemia of malignancy would benefit from the development of agents that can selectively reduce the renal tubular reabsorption of calcium. In patients displaying a good response to clodronate, the fall in plasma calcium is accompanied by an increase in the calcium-regulating hormones, parathyroid hormone and 1,25-dihydroxyvitamin D3. This homeostatic reaction probably explains why hypocalcemia rarely occurs in clodronate-treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clodronate in hypercalcemia of malignancy. 213 62

Many factors, such as interleukin 1, TGF alpha, TNF alpha, and beta and prostaglandins, have been implicated in aetiological roles in HHM (Martin and Mundy, 1987). Much interest in the past has also centered 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 prepropeptide 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 NH2-terminus 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 for 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 a similar intron/exon organization as 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 enabled detailed structure-function studies that have identified NH2-terminal 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 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 hypercalcemia. 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 hypercalcemia, 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 fetal calcium metabolism and in normal cell physiology.
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PMID:A novel parathyroid hormone-related protein: role in pathology and physiology. 218 38

During the past decade, specific mediators of bone destruction in hypercalcemia of malignancy have been identified and characterized. These humoral factors include parathyroid hormone-related protein, transforming growth factor alpha, and cytokines such as interleukin-1 and tumor necrosis factor. In metastatic hypercalcemia associated with breast cancer, prostaglandin secretion by tumor cells may be one of the important factors. Among the osteoclast activating factors associated with hypercalcemia in patients with myeloma, lymphotoxin plays a central but probably not exclusive role. Alterations of renal function in hematologic hypercalcemia may potentiate bone destruction that usually occurs in the presence of impaired rates of glomerular filtration. Further research is required to determine the relative contributions of bone and kidney to the pathogenesis of hypercalcemia of malignancy.
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PMID:Pathophysiology of cancer-associated hypercalcemia. 218 48

Hypercalcemia, a complication that develops in 10% to 20% of patients with cancer, results from disruption of the normal physiologic mechanisms that closely regulate calcium homeostasis. Most patients with hypercalcemia are seriously dehydrated, and this volume depletion further compromises the kidney's ability to excrete calcium. Replenishment of extracellular fluid, restoration of intravascular volume, and maintenance of saline diuresis are the cornerstones of initial therapy. In most patients, pharmacologic inhibition of abnormally increased osteoclastic resorption is necessary to normalize serum calcium and achieve long-term control. The severity of the hypercalcemia and the patient's renal function, bone marrow reserve, and anticipated response to specific antineoplastic agents can all influence the selection of an antihypercalcemic agent. Available drugs for initial therapy include calcitonin, plicamycin, and etidronate; several additional investigational agents have shown promising efficacy in controlling hypercalcemia of malignancy. The bisphosphonates have an excellent safety profile and appear to be the agents of choice for initial and long-term management of cancer-related hypercalcemia.
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PMID:Treatment of cancer-related hypercalcemia. 218 50

Hypercalcemia is one of the most serious metabolic disorders associated with cancer. The incidence and clinical circumstances associated with hypercalcemia vary in different types of cancer. Hypercalcemia is the most frequent metabolic complication of breast cancer and is usually related to widespread osteolytic metastases; however, local and systemic humoral factors mediating bone resorption have been described. In some patients with breast cancer, hypercalcemia results from treatment with estrogens, antiestrogens, androgens, or progestins. Coexisting primary hyperparathyroidism rarely confounds the diagnosis. In patients with lung cancer, the incidence of hypercalcemia varies with histology and is often unrelated to bone metastases. Hypercalcemia may occur either late or early in the disease but is seldom a presenting symptom. In patients with cancers of the head and neck region, hypercalcemia is most often associated with advanced recurrent and terminal disease, presumably humorally mediated. In renal cell carcinoma, hypercalcemia is also an adverse prognostic indicator, commonly mediated by humoral factors. On the other hand, almost all patients with multiple myeloma have extensive osteolytic bone destruction and hypercalcemia is frequently a presenting symptom. Hypercalcemia is uncommon in most lymphomas; however, it is usually a prominent feature of adult T-cell lymphomas and also occurs in some large cell, diffuse B-cell lymphomas. Awareness of the setting in which hypercalcemia of malignancy occurs will lead to its prompt diagnosis and institution of appropriate therapy.
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PMID:Overview of cancer-related hypercalcemia: epidemiology and etiology. 218 51


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