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

Osteoporosis is the most important metabolic bone disease and places an increasing burden on the healthcare system. The condition can be prevented by the early introduction of hormone replacement therapy. The role of bisphosphonates in achieving the same result is being actively explored. The attraction of preventing bone loss is that it preserves the micro-architecture of bone, and therefore its mechanical integrity. The great problem of treating the established condition is that substantial bone loss is accompanied by architectural disintegration. Replacing lost bone may not necessarily restore mechanical integrity and protect against fractures. The management of Paget's disease has been quite revolutionised by the introduction of the bisphosphonates. The condition is a result of a primary increase in osteoclastic bone resorption which can be corrected by bisphosphonates, with considerable symptomatic improvement. The increasing potency and safety margin of the newer agents has meant that the threshold for treatment has fallen. There is now potential for long term control of bone turnover with the hope of preventing late complications. Hypercalcaemia of malignancy is usually the result of both increased bone destruction and decreased urinary calcium excretion. These two components of hypercalcaemia demand different approaches to management. The general availability of an ever-expanding range of increasingly potent bisphosphonates has resulted in a dramatic improvement in the treatment of increased bone resorption associated with malignancy. Many types of tumour, either directly or indirectly, compromise the ability of the kidney to eliminate a calcium load derived from increased bone destruction. Calcitonin is the only agent which is currently available to counter this process.
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PMID:Drugs used in the treatment of metabolic bone disease. Clinical pharmacology and therapeutic use. 750 48

Hypercalcemia of malignancy is most commonly due to the effects of parathyroid hormone-related peptide, which acts as a humoral factor to cause generalized osteoclast-mediated bone resorption and reabsorption of calcium by the kidney tubule, and may also act as a local resorptive factor adjacent to bone metastases. Local resorptive mechanisms are less common causes of malignant hypercalcemia than previously believed. Treatment begins with intravenous fluid rehydration, followed by a furosemide diuresis and the bisphosphonate pamidronate, 60-90 mg, intravenously. Gallium nitrate is an efficacious but inconvenient alternative to pamidronate. Calcitonin combined with pamidronate is a reasonable initial therapy for severe hypercalcemia to hasten normalization of the serum calcium. Steroids should be reserved for hypercalcemia due to tumor production of 1,25 dihydroxyvitamin D, or for steroid-responsive malignancies. Oral or parenteral bisphosphonates can be used to maintain normocalcemia. In addition to improving the morbidity of acute hypercalcemia, bisphosphonate therapy has been shown to reduce bone pain and pathological fractures in patients with bone metastases, and calcitonin also has a potent analgesic effect in these patients. Treatment for hypercalcemia should therefore be considered in the majority of patients in the palliative care setting.
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PMID:Hypercalcemia of malignancy in the palliative care patient: a treatment strategy. 754 27

Hypercalcemia is the most common paraneoplastic syndrome associated with cancer. This paper addresses the etiology and pathogenesis of hypercalcemia of malignancy and discusses the relative contributions of local and humoral effects on bone and renal calcium homeostasis. The roles of parathyroid hormone-related protein and other osteolytic cytokines are outlined. New biochemical markers that enable more specific monitoring of the response of bone metastases to treatment are introduced, including urinary excretion of the collagen crosslinks pyridinoline and deoxypyridinoline. The clinical management and prevention of hypercalcemia is systemically outlined, including indications for bisphosphonate, glucocorticoid, and calcitonin therapy. The results of recent trials of bisphosphonate therapy for the prevention of tumor progression and its subsequent problems such as bone pain, fracture, and hypercalcemia also are discussed.
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PMID:Hypercalcemia and bone resorption in malignancy. 763 18

Bisphosphonates are analogues of inorganic pyrophosphate, a naturally occurring chemical in bone. In vitro and animal experiments demonstrated that these agents were effective inhibitors of bone resorption. Subsequently they were applied to a variety of clinical problems in which increased bone resorption was an underlying feature of the pathology. In 1971 etidronate became the first bisphosphonate shown to inhibit bone resorption in humans when it was given to patients with Paget's disease. Subsequently this agent was also found to be useful in treating the hypercalcemia of malignancy. At the present time cyclic etidronate therapy is also used for the prevention of bone loss in patients with osteoporosis and for the prevention of heterotopic ossification in spinal cord-injured patients and in patients after hip replacement. Newer bisphosphonates are generally more potent than etidronate and do not produce a severe mineralization defect as do higher doses of etidronate. Pamidronate and clodronate are highly effective in the management of Paget's disease, hypercalcemia due to malignancy and immobilization, metastatic bone disease, and hematologic malignancies affecting bone. They are also promising agents for the prevention of osteoporosis. Alendronate, risedronate, and CGP 42446 are highly potent bisphosphonates that look very promising for the treatment of all disorders of bone resorption. It is fortunate that adverse reactions are not a prominent feature of bisphosphonate use. The main side effects are nausea and abdominal discomfort, mainly with oral use, a transient increase in bone pain in patients with Paget's disease, and an acute-phase reaction (fever, myalgia, mild leukopenia) in patients receiving aminobisphosphonates. The evolution of bisphosphonate therapy should be considered one of the major therapeutic events of the past 25 years. Future research should define the optimum use of these agents.
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PMID:Bisphosphonates in the treatment of disorders of mineral metabolism. 767 Oct 99

Humoral hypercalcemia of malignancy (HHM) is a common paraneoplastic syndrome mediated by tumor-derived parathyroid hormone-related peptide (PTHRP), which bears structural and functional similarities to PTH. Thus the clinical features of HHM are very similar to those of primary hyperparathyroidism (1 degree HPT), a prototype of humoral hypercalcemia caused by PTH. On the other hand, HHM syndrome differs from 1 degree HPT in several aspects, including serum 1,25(OH)2D levels, acid-base balance, and bone remodeling process, the reason of which remains largely unknown. We approached these questions using a unique animal model of HHM, nude rats implanted with PTHRP-overproducing human carcinomas. In this review we will summarize the results and discuss the implications in understanding the disease mechanism.
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PMID:Humoral hypercalcemia of malignancy: some enigmas on the clinical features. 776 74

Hypercalcemia of malignancy is due either to local osteolysis at the site of bone metastases or to production by the malignancy of parathyroid hormone-related peptide, which shares some of the effects of parathyroid hormone. We used a radioimmunoassay (antiserum specific to the amino-terminus) to measure serum parathyroid hormone-related peptide levels in controls (n = 61), chronic renal failure patients (n = 10), patients with primary hyperparathyroidism (n = 19), cancer patients with (n = 35) or without (n = 57) hypercalcemia and/or bone metastases (n = 53 and n = 39, respectively), and patients with hematologic malignancies (n = 15). We set the upper limit of normal of the parathyroid hormone-related peptide assay at 2.7 pmol/L. The peptide was undetectable in two-thirds of healthy controls. Renal failure did not interfere with the assay. Eighteen of the 19 patients with primary hyperparathyroidism had normal levels. In contrast, 82% of patients with humoral hypercalcemia of malignancy (i.e., without detectable bone metastases) had increased levels; in this subgroup there was a significant inverse correlation between serum levels of the peptide and phosphorus. Elevation of parathyroid hormone-related peptide levels was less common among hypercalcemic patients with metastatic bone disease (38%). Four of the seven hypercalcemic patients with hematologic malignancies had elevated parathyroid hormone-related peptide levels. In our overall study population, serum calcium levels were weakly but significantly correlated with parathyroid hormone-related peptide levels. In conclusion, elevated parathyroid hormone-related peptide in a patient with hypercalcemia suggests a malignant disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Contribution of parathyroid hormone-related peptide to the evaluation of hypercalcemia. 778 31

Hypercalcemic crisis or severe hypercalcemia represents a life-threatening emergency. The most common cause is hypercalcemia of malignancy, although granulomatous diseases, previously undetected primary hyperparathyroidism, medication-induced hypercalcemia, and a few rarer causes may result in this endocrine emergency as well. The clinical presentation and prognosis depend on the acuity of the development of hypercalcemia, the degree of hypercalcemia, and the underlying cause. Certainly, patients with malignancy who develop hypercalcemia superimposed on their already debilitated state are more likely to have a poor outcome than a previously relatively healthy patient with thiazide-induced hypercalcemia, for example. The clinical presentation of patients with hypercalcemic crisis varies depending once again on the underlying cause and degree and rapidity of the hypercalcemia. Most patients experience some constitutional symptoms, neurologic symptoms, gastrointestinal symptoms, and renal manifestations of hypercalcemia. Immediate and effective therapy directed toward the pathophysiology of hypercalcemia is essential. General measures must be implemented to reverse the dehydration, to promote urinary calcium excretion, to avoid prolonged immobilization, and to identify the underlying cause of hypercalcemia. Specific measures directed at inhibiting bone resorption, increasing renal sodium and calcium excretion, and occasionally at decreasing intestinal absorption of calcium (or more specifically blocking vitamin D metabolism) should also be implemented. Obviously the more reversible the underlying cause of hypercalcemia, the more aggressive one should be with the therapy. The literature was reviewed to compile comparative data that practitioners may use in choosing among the various pharmacologic therapies available for the treatment of acute hypercalcemia. Despite all the advances in the field, hypercalcemic crisis still carries a significant mortality risk, although with appropriate therapy with the aforementioned general and specific measures, the calcium level can effectively be lowered in most patients.
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PMID:Hypercalcemic crisis. 780 96

Parathyroid hormone-related protein (PTHrP) is the factor responsible for the syndrome of humoral hypercalcemia of malignancy (HHM). The syndrome is well documented in adult cancer patients, but has not previously been described in young children. We report the case of a 3-month-old infant who developed refractory hypercalcemia (peak total calcium 13.8 mg/dl; normal 8.5-10.5, ionized calcium 3.3 meq/l; normal 2.0-2.5) associated with a high-grade, poorly differentiated malignant hepatic sarcoma. Parathyroid hormone (intact) levels were suppressed (7.5 pg/ml; normal 10-65). Fractional excretion of phosphate was markedly elevated (73.5%; normal 8%-20%) as were urinary cAMP levels (12.48 nmol/dl glomerular filtrate; normal 1.83-4.47) suggesting a PTH-like effect. Increased levels of PTHrP were present both in the serum (4.9 pmol/l; normal for adults < 1.5) and ascitic fluid (6.1 pmol/l). Since previous studies have demonstrated a potential role for PTHrP in the regulation of embryonal tissue differentiation and transmembrane calcium flux, our observation of elevated PTHrP levels associated with the development of a poorly differentiated hepatic sarcoma in a young infant may provide insight into the molecular mechanisms underlying HHM. We suggest that serum or plasma PTHrP levels be determined in all children with hypercalcemia of malignancy in whom the hypercalcemia cannot otherwise be explained.
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PMID:Fatal parathyroid hormone-related protein-induced humoral hypercalcemia of malignancy in a 3-month-old infant. 781 27

Humoral hypercalcemia of malignancy is a paraneoplastic syndrome believed to be due to production by the tumor of substances that stimulate osteoclastic bone resorption primarily. The human renal cell carcinoma cell line RC-8, grown in nude mice, was investigated for factors involved in renal cancer-induced hypercalcemia. At a tumor load of 200 to 400 mm.3 the mice developed hypercalcemia and hypophosphatemia associated with a rise in serum 1,25-dihydroxyvitamin D concentration and cachexia. The tumor released 1) significant amounts of human interleukin-6 (IL-6) and 2) parathyroid hormone-related peptide (PTHrP) into the circulation. Cancer cells further expressed mRNA for both human IL-6 and PTHrP. No secretion of human tumor necrosis factor-alpha or interleukin-1 beta could be demonstrated in the circulation of the host. Antibodies to IL-6 caused a significant (p = 0.043) inhibition of tumor growth and decreased serum calcium concentrations compared with control animals. Our data suggest that IL-6 is involved, either directly or indirectly, in the development of hypercalcemia in renal cell carcinoma.
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PMID:Hypercalcemia and cosecretion of interleukin-6 and parathyroid hormone related peptide by a human renal cell carcinoma implanted into nude mice. 786 50

Milk-alkali syndrome can be caused by ingesting large amounts of calcium carbonate. Coincident with the promotion of calcium carbonate as treatment for both dyspepsia and osteoporosis, milk-alkali syndrome is now a common cause of hypercalcemia severe enough to require admission to the hospital. The syndrome accounted for less than 2% of such admissions before 1990, but from 1990 through 1993, it was the cause of hypercalcemia for over 12% of these patients. Only primary hyperparathyroidism and hypercalcemia of malignancy (excluding multiple myeloma) are more common. The diagnosis of milk-alkali syndrome is made almost entirely based on the patient's history; careful attention to dietary practices and over-the-counter drug use is required, as numerous over-the-counter medications contain calcium carbonate. Modern assays for PTH demonstrate the expected suppression of PTH by hypercalcemia. Nonetheless, measurement of PTH must be performed in a timely manner as treatment with intravenous saline may result in hypocalcemia and elevated PTH soon after admission. Given the pathophysiology of milk-alkali syndrome compared to other causes of hypercalcemia, hypocalcemia with rebound hyperparathyroidism is probably unique to milk-alkali syndrome.
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PMID:Milk-alkali syndrome associated with calcium carbonate consumption. Report of 7 patients with parathyroid hormone levels and an estimate of prevalence among patients hospitalized with hypercalcemia. 789 47


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