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)

The purpose of this study was to assess the diagnostic utility of parathyroid ultrasonography to differentiate causes of hypercalcemia in dogs. We analyzed qualitative and quantitative ultrasound imaging findings and clinical pathology data from 33 dogs that underwent parathyroid ultrasound examination as part of the diagnostic evaluation for hypercalcemia. Diagnoses of the diseases causing hypercalcemia included parathyroid carcinoma (n = 5), parathyroid adenoma (n = 15), parathyroid adenomatous hyperplasia (n = 6), chronic renal insufficiency (n = 3), and hypercalcemia of malignancy (n = 4). All parathyroid lesions were round or oval and hypoechoic compared with surrounding thyroid parenchyma. Adenomatous and adenocarcinomatous glands were 4 mm or larger in longest linear measurement on US examination and were statistically significantly larger than hyperplastic glands. (p < 0.001) Linear measurements of parathyroid glands acquired at the time of ultrasound examination correlated well with direct size determination after surgical excision. (r2 = 0.9, p < 0.0001) Parathyroid lesions > or = 4 mm are highly suspicious for parathyroid adenoma or carcinoma, while US lesions < 4 mm most likely represent primary adenomatous hyperplasia or secondary parathyroid hyperplasia. Parathyroid size estimation from ultrasound examination is an accurate predictor of true size.
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PMID:High-resolution parathyroid sonography. 940 14

Human hypercalcemia of malignancy (HHM) is generally due to the release into the circulation of parathyroid hormone-related peptide (PTHrP). PTHrP stimulates osteoclastic bone resorption and renal calcium reabsorption through the activation of a receptor similar to that of PTH (PTH-R). However, there is scarce information about the PTH-R regulation in the setting of the hypercalcemia. In the present study, we assessed the molecular basis of renal PTH-R regulation in Walker tumor-bearing rats either treated or not by a bisphosphonate, pamidronate. Twenty-seven 6-week-old rats were randomly divided into three experimental groups: WC- APD- (9 control rats), WC+ APD- (9 Walker tumor-bearing rats), and WC+ APD+ (9 Walker tumor-bearing rats receiving 15 mg/kg/day of sodium pamidronate every day for seven days). Pamidronate induced a significant decrease in the mean tumor weight (9.3+/-0.8 vs 6.3+/-0.6 g). Seven days after the subcutaneous implantation of the Walker cells, plasma total calcium was 10.8+/-0.4, 16.8+/-0.6, and 12.9+/-0.6 mg/dl in WC- APD-, WC+ APD-, and WC+ APD+, respectively. Plasma PTHrP concentration was undetectable, 15.9+/-2.6, and 7.2+/-1.4 pmol/l, respectively. Bone histomorphometric results showed high resorption in WC+ APD-, which returned below the basal level of the WC- APD- with pamidronate treatment. Densitometric analysis of Northern blots revealed that the renal PTH-R mRNA expression in WC+ WPD- rats was a quarter of the levels in the WC- APD- and WC+ APD+ groups. WC+ APD- also had a decreased PTH-stimulated cAMP production in renal membranes. The PTH-R was expressed in the Walker tumor and it was not modified by pamidronate treatment. In conclusion, the expression of PTH-R receptor mRNA is significantly reduced in the kidney of rats bearing Walker carcinoma tumor. Its regulation is tissue-specific: pamidronate, which partially corrected the hypercalcemia and elevated circulating PTHrP, normalized the PTH-R mRNA expression in the kidney but not in the tumor.
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PMID:Pamidronate corrects the down-regulation of the renal parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor mRNA in rats bearing Walker tumors. 966 83

The purpose of the present study was to review the literature with respect to the prevalence of hypercalcaemia in normal and in hospital populations. Pertinent studies were selected from the MEDLINE database (1980 to March 1995) and through the bibliographies of selected articles. Hypercalcaemia is one of the most common metabolic disorders in malignant diseases and develops in 3-30% of such patients. Hypercalcaemia of malignancy is the most common cause of hypercalcaemia followed by primary hyperparathyroidism in hospital populations. The most common cause in normal populations is primary hyperparathyroidism followed by transient hypercalcaemia. The prevalence of hypercalcaemia shows a large variation in hospital populations ranging from 0.17% to 2.92%. The prevalence in normal populations varies between 1.07% and 3.9% and, surprisingly exceeds the level in hospital populations. The discrepancies between prevalences may be due to varying referral patterns, different distribution of specialities causing different hospital populations and different definitions of hypercalcaemia. Hypercalcaemia presents a diagnostic problem. The percentage of cases of hypercalcaemia that are actually diagnosed has been observed to be as low as 25% in hospitals, in which laboratory results remain unreported unless requested. But even when presented, 20-50% of the cases are overlooked.
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PMID:Prevalence of hypercalcaemia in normal and in hospital populations. 977 94

Hypercalcaemia of malignancy is a frequent occurrence. First line treatment of this condition involves the use of bisphosphonates. This report sets out the clinical findings in a patient presenting with metastatic breast cancer and hypercalcaemia (corrected serum calcium 3.72 mmol/l) who had received previous surgery for a parathyroid adenoma. After treatment with pamidronate, profound, prolonged (more than 60 days) symptomatic hypocalcaemia was observed. We discuss the possible explanations for these observations and conclude that a normal parathyroid reserve is probably necessary for the smooth normalization of blood calcium when bisphosphonates are used to treat malignant hypercalcaemia.
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PMID:Severe prolonged hypocalcaemia following pamidronate for malignant hypercalcaemia. 989 May 46

Hypercalcemia was discovered in a 7-year-old, castrated male basset hound with a suspected nasal tumor. The dog died the day after admission and nasal carcinoma and disseminated intravascular coagulation were diagnosed on postmortem. Detectable levels of serum PTHrP support a diagnosis of hypercalcemia of malignancy.
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PMID:Hypercalcemia and parathyroid hormone-related protein in a dog with undifferentiated nasal carcinoma. 1034 96

Alendronate is a powerful therapeutic agent for the treatment of hypercalcemia in malignancy and osteoporosis and has recently been developed as a treatment for hypercalcemia of malignancy. In this study, time-lapse cinemicrography was used to investigate the effects of this agent on the morphology and the motility of human osteoclast-like multinucleated cells (MNCs) from human bone marrow. Alendronate at 10(-5)M induced contraction of the cells starting 7.5 h after its addition. Contraction was markedly induced immediately after alendronate removal. However, contraction almost disappeared 18h after removal, and osteoclast-like MNCs recovered their original sizes and shape. There was only partial recovery from contraction after alendronate treatment at 10(-4)M. In contrast, untreated control cells did not change their morphology after washing with culture medium. Motility analysis showed that osteoclast-like MNCs treated with 10(-5)M alendronate moved actively after washing, but at 10(-4)M the motility locus was very narrow. At 10(-4)M, the actin ring in the cells began to break down, beginning 6h after addition. The effects of alendronate on human osteoclast-like MNCs morphology and motility were reversible at 10(-5)M, suggesting that alendronate dose not cause any cellular damages in human osteoclasts up to 10(-5)M, which is an effective dose for bone resorption.
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PMID:Reversibility of alendronate-induced contraction in human osteoclast-like cells formed from bone marrow cells in culture. 1034 Jun 36

Humoral hypercalcemia of malignancy is a cancer-related hypercalcemia caused by production of humoral factors by malignant cells in patients without bone metastases. Squamous cell carcinomas are the tumors most frequently associated with humoral hypercalcemia of malignancy, and parathyroid hormone-related protein is the main humoral factor implicated. In spite of the fact that normal keratinocytes produce parathyroid hormone-related protein, it is highly unusual for patients with squamous cell carcinomas of the skin to present with humoral hypercalcemia of malignancy. We present a well-documented case of cutaneous squamous cell carcinoma complicated by hypercalcemia in a patient with high levels of plasma parathyroid hormone-related protein and immunohistochemical evidence of high parathyroid hormone-related protein production by the tumoral cells.
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PMID:Immunohistochemical detection of parathyroid hormone-related protein in a cutaneous squamous cell carcinoma causing humoral hypercalcemia of malignancy. 1042 Feb 32

Calciphylaxis is a rare disorder associated with calcification of small- and medium-sized blood vessels, and progressive skin necrosis usually seen in the setting of end-stage renal disease (ESRD) and secondary hyperparathyroidism. It has also been observed in primary hyperparathyroidism, hypercalcemia of malignancy (extensive bony metastasis of breast cancer), and an isolated case reported with end-stage liver disease. We report an unusual case of calciphylaxis associated with metastatic breast carcinoma in the absence of renal or parathyroid disease. Calciphylaxis has generally been associated with end-stage renal disease and hyperparathyroidism. One previous case report described calciphylaxis occurring in a patient with metastatic adenocarcinoma of the breast and hypercalcemia. Our case represents the second reported case of calciphylaxis associated with osteolytic, metastatic breast cancer. Although ESRD with secondary hyperparathyroidism is the most common presentation of calciphylaxis, this case demonstrates that other conditions that alter normal calcium metabolism must be considered in the differential diagnosis.
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PMID:Calciphylaxis associated with metastatic breast carcinoma. 1042 13

The pathogenesis of hypercalcemia of malignancy comprises increased net bone resorption and enhanced renal tubular reabsorption of calcium (Ca). To evaluate the prevalence of an increased renal tubular reabsorption of Ca index [tubular reabsorption of calcium index (TRCaI)] in cancer patients with hypercalcemia and of elevated circulating levels of PTH-related protein (PTHrP), which is recognized as a major mediator of this syndrome, we investigated 315 well rehydrated patients, aged 58.1 +/- 0.7 yr (mean +/- SEM), with hypercalcemia [albumin-corrected plasma Ca (pCa), >2.7 mmol/L] secondary to histologically proven malignancy. Changes in pCa and, therefore, various Ca filtered loads were obtained by different degrees of bone resorption inhibition achieved with a single infusion of the bisphosphonate ibandronate, given at various doses on a randomized, double blind basis. PTHrP was determined at baseline in 147 of the patients and 7 days after bisphosphonate therapy in 73. Before ibandronate therapy, pCa was 3.36 +/- 0.02 mmol/L, mean TRCaI was increased at 3.09 +/- 0.03 mmol/L glomerular filtration rate (GFR; normal, 2.40-2.90), and 65% of patients had TRCaI above 2.90 mmol/L GFR. Mean serum PTHrP levels were 4.9 +/- 0.5 pmol/L (normal, <2.5) and values above the normal range were found in 53% of the patients (76% in lung and upper respiratory tract malignancies). By 7 days after the infusion of ibandronate, a decrease in pCa of 0.69 +/- 0.03 mmol/L (20.0 +/- 0.7%; P < 0.001) and in bone resorption [mean change in fasting urinary Ca, 0.09 +/- 0.04 mmol/L GFR (47.6 +/- 8.6%; P < 0.001) and 14.4 +/- 1.7 nmol/mmol (27.6 +/- 10.6%; P < 0.01) in deoxypyridinoline] was observed. TRCaI was slightly lowered by 0.30 +/- 0.09 mmol/L GFR. Mean changes in PTHrP, 1,25-dihydroxyvitamin D3, and PTH were +0.7 +/- 0.4 (P = NS), +27.6 +/- 3.0 (P < 0.001), and +2.9 +/- 0.8 (P < 0.005) pmol/L, respectively. After ibandronate treatment, the relative risk of relapsing hypercalcemia was particularly increased (3.43-fold) in lung and upper respiratory tract malignancies. These results obtained in a large cohort of patients indicate a significant prevalence of an increased renal tubular reabsorption of calcium index in hypercalcemia of malignancy and a substantial proportion of patients with detectable PTHrP.
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PMID:Serum parathyroid hormone-related protein levels and response to bisphosphonate treatment in hypercalcemia of malignancy. 1052 93

Bisphosphonates are synthetic analogues of pyrophosphate that inhibit bone resorption by their action on osteoclasts. Bisphosphonates have been extensively used in the elderly with primary and secondary osteoporosis, Paget's disease, and hypercalcemia of malignancy. In recent years, bisphosphonates have been used to treat children acutely for resistant hypercalcemia and chronically for various metabolic bone diseases. The theoretical concerns of possible adverse effects of these drugs on the growing skeleton have not been proven to be true. In the present review, we have critically analyzed the available literature on bisphosphonate therapy in both adult and pediatric clinical trials. Although not yet approved by the FDA for use in children, bisphosphonates, from published experience, demonstrate benefit to the child with no serious adverse effects. Based on the literature analysis the review furnishes detailed recommendations and practical guidelines regarding the use of oral and intravenous bisphosphonates in children. Bisphosphonates might be the first agents to provide the pediatrician with an opportunity to treat mineral and bone disorders of childhood, which until recently did not have satisfactory therapy.
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PMID:Bisphosphonates: from grandparents to grandchildren. 1061 61


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