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

In an attempt to analyze the pathological processes which lead to hypercalcemia in patients with multiple bone metastases, 23 advanced breast cancer patients with multiple bone metastases, three hypercalcemic patients with other malignancies and seven early breast cancer patients without any distant metastasis were studied. Of the 23 patients with advanced breast cancer, nine showed serum calcium levels higher than 10 mg/dl. In five of the nine hypercalcemic patients with advanced breast cancer, urinary cyclic AMP excretion was lower than 4 nmol/100 ml of glomerular filtrate (GF), indicating that the secretion of parathyroid hormone was suppressed. However, urinary cyclic AMP excretion was higher than 4 nmol/100 ml of GF in the other four hypercalcemic patients with advanced breast cancer and three hypercalcemic patients with other malignancies. In patients with higher urinary cyclic AMP excretion, fractional excretion of calcium (FECa) showed a negative correlation (r = 0.83, P less than 0.05) with urinary cyclic AMP. Parathyroid hormone immunoreactivity was not detected in any of six patients showing serum calcium levels higher than 11 mg/dl. These results suggest that in about a half of hypercalcemic patients with advanced breast cancer and multiple bone metastasis, there is a factor which increases urinary cyclic AMP and enhances calcium reabsorption in the kidney, but which is different from parathyroid hormone. This factor may facilitate retention of calcium mobilized into the circulation by bone metastases, and lead to hypercalcemia.
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PMID:Stimulation of calcium reabsorption observed in advanced breast cancer patients with hypercalcemia and multiple bone metastases. 298 61

A serially transplantable tumor line, designated CAC-8, has been developed in nude mice from a spontaneously occurring adenocarcinoma of the anal sac from a hypercalcemic dog. Nude mice with transplanted CAC-8 developed hypercalcemia (mean 16.3 +/- 0.6 mg/dl) and moderate hypophosphatemia without bone metastasis. Urinary excretion of calcium and hydroxyproline were increased 6- and 2.3-fold, respectively. Urinary excretion of cAMP was moderately increased but phosphorus excretion was not significantly altered. Serum 1,25-dihydroxycholecalciferol was increased significantly in tumor-bearing nude mice in proportion to the magnitude of tumor-induced hypercalcemia. Histomorphometric evaluation of lumbar vertebrae from nude mice with CAC-8 revealed decreased total and cortical bone volume, a 3.3-fold increase in bone resorption rate and a 2.5-fold increase in bone formation rate at the tissue level. The transplanted CAC-8 has maintained the histologic pattern of the original carcinoma up to the present sixth passage. Ultrastructural evaluation of transplanted tumor cells revealed 150-250-nm secretory-like granules. The granules did not stain by using an ultrastructural cytochemical (uranaffin) stain specific for neuroendocrine secretory granules. Ultrastructurally, the parathyroid glands of nude mice with CAC-8 appeared inactive with large intracytoplasmic whorl of agranular membranes. These data suggest the transplanted carcinoma secreted a humoral factor which resulted in hypercalcemia. The tumor line (CAC-8) propagated in nude mice represents an animal model of humoral hypercalcemia of malignancy that shares many features with the syndrome described in human patients. Unique features of this transplanted carcinoma associated with hypercalcemia include increased serum dihydroxycholecalciferol, increased rate of bone formation as well as bone resorption, an absence of bone metastases, and evidence of parathyroid gland suppression.
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PMID:Humoral hypercalcemia of malignancy in nude mouse model of a canine adenocarcinoma derived from apocrine glands of the anal sac. Biochemical, histomorphometric, and ultrastructural studies. 301 99

Treatment of malignancy-associated hypercalcemia remains unsatisfactory. We have prospectively treated 26 consecutive hypercalcemic cancer patients with intravenous (IV) aminohydroxypropylidene diphosphonate (APD). The drug was administered daily as a 15-mg two-hour IV infusion until both serum and urinary calcium had been normalized for 48 hours. Twenty-four patients were fully evaluable (eight head and neck tumors, seven breast cancers, three epidermoid tumors of the lung, and six miscellaneous neoplasms). Whereas rehydration had only inconsistent effects, APD normalized serum calcium in all patients after a mean of three daily doses: serum calcium decreased from 13.3 +/- 0.4 mg/dL (mean +/- SEM) before APD to 8.0 +/- 0.1 mg/dL at the end of treatment. Ionized calcium declined in parallel to total calcium. APD was as effective in hypercalcemia due to bone metastases as in paraneoplastic hypercalcemia. The drug was tolerated without toxicity and had a prolonged effect: serum calcium remained normal during 3+ weeks (1 + to 8 +) in 17 patients who did not receive or did not respond to antitumoral treatment. APD normalized serum calcium by inhibiting bone resorption, as evidenced by the dramatic decrease in urinary excretion of calcium and hydroxyproline. Inhibition of bone resorption was probably also responsible for the decrease in serum phosphorus from 2.9 +/- 0.2 to 2.0 +/- 0.1 mg/dL. In summary, IV APD constitutes a major advance in the treatment of malignancy-associated hypercalcemia: it is very effective, well tolerated, and has a prolonged efficacy.
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PMID:Treatment of malignancy-associated hypercalcemia with intravenous aminohydroxypropylidene diphosphonate. 301 5

Specific high affinity receptors for 1,25-dihydroxyvitamin D3 are present in several human breast cancer cell lines, and this hormone can regulate the replication of these cells. These receptors are also present in primary breast carcinomas. The present study has resulted from the follow-up for up to 68 mo of 263 women, who had had 1,25-dihydroxyvitamin D receptor (1,25-DR) levels measured in their primary tumors. Survival data on 191 women were correlated with the levels of 1,25-DR and other steroid hormone receptors, menopausal status, and age by life table analysis. Survival was not affected by 1,25-DR level in either absolute terms or relative levels. However, the late development of lymph node metastases in eight of 47 individuals was correlated with the 1,25-DR level (P = 0.05). There was no correlation between 1,25-DR or other hormone receptor levels and the development of hypercalcemia or bone metastases in the small number of individuals so affected. As we had observed previously, there was no correlation between the level of 1,25-DR and that of the other steroid hormones. These data show that the presence of 1,25-DR in primary breast cancers is independent of other prognostic indicators and, inasmuch as it correlated with late lymph node metastasis, may be an adverse prognostic indicator.
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PMID:Significance of 1,25-dihydroxyvitamin D3 receptor in primary breast cancers. 301 26

Hypercalcemia, often associated with certain types of adult tumors, has also been described in pediatric neoplasms. In childhood, the more common associations include lymphoma, leukemia, rhabdomyosarcoma and rarely neuroblastoma. However, recently, several infants with hypercalcemia were described having renal tumors without bone metastases. The following is a case report of a 2-month-old infant who presented with severe hypercalcemia and a large right-sided abdominal mass, which at surgery was diagnosed as a cellular mesoblastic nephroma.
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PMID:Hypercalcemia in association with mesoblastic nephroma: report of a case and review of the literature. 302 25

Gallium, a group IIIa metal, is known to interact with hydroxyapatite as well as the cellular components of bone. In recent studies we have found gallium to be a potent inhibitor of bone resorption that is clinically effective in controlling cancer-related hypercalcemia as well as the accelerated bone resorption associated with bone metastases. To begin to elucidate gallium's mechanism of action we have examined its effects on bone mineral properties. After short-term (14 days) administration to rats, gallium nitrate produced measurable changes in bone mineral properties. Using atomic absorption spectroscopy, low levels of gallium were noted to preferentially accumulate in regions of active bone formation, 0.54 +/- .07 microgram/mg bone in the metaphyses versus 0.21 +/- .03 microgram/mg bone in the diaphyses, P less than 0.001. The bones of treated animals had increased calcium content measured spectrophotometrically. Rats injected with radiolabeled calcium during gallium treatment had greater 45-calcium content compared to control animals. By wide-angle X-ray analyses, larger and/or more perfect hydroxyapatite was observed. The combined effects of gallium on bone cell function and bone mineral may explain its clinical efficacy in blocking accelerated bone resorption.
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PMID:Gallium increases bone calcium and crystallite perfection of hydroxyapatite. 302 92

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

In a case of pancreatic endocrine carcinoma hypercalcaemia without bone metastases and normal parathyroid glands prompted our suspicion that there was paraneoplastic production of an osteoclast activating substance by the tumour tissue. This view was further confirmed by bone histology. Immunohistology post mortem revealed the production of PTH in the primary tumour and a liver metastasis. The usefulness of immunohistology in detecting paraneoplastic secretion of hormonal substances is discussed.
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PMID:Pancreatic endocrine carcinoma with ectopic PTH-production and paraneoplastic hypercalcaemia. 308 66

Fourteen cases of urogenital tumors (9 prostatic carcinomas, 4 renal cell carcinomas and 1 bladder carcinoma) which had bone metastases were treated with eel-calcitonin, Elcitonin injections for relief of bony pain. Forty mgs. of Elcitonin was injected intramuscularly, 2 to 3 times a week, to out-patients. Forty to 80 mgs. of Elcitonin was injected intramuscularly, daily to hospitalized patients. Relief of the pain was obtained in 71.4% of all patients (71.4% of out-patients and 71.4% of hospitalized patients) and especially in 88.9% of prostatic carcinoma patients. Hypercalcemia was seen in only one patient of renal cell carcinoma. It is considered that Elcitonin treatment is useful for relief of bony pain in the patients with bone metastases, with or without hypercalcemia.
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PMID:[Experience of Elcitonin treatment in metastatic bony pain of urological tumors]. 317 47

Serum osteocalcin (BGP) is an osteoblast product that probably reflects the rate of bone formation. It is a potential marker of skeletal metastases and, to investigate this, BGP was measured by radioimmunoassay in the serum of normal subjects and patients with breast or prostate cancer. Significantly higher levels were found in patients with metastatic bone disease in comparison to both normal subjects (P less than 0.001) and patients with non-metastatic cancer (P less than 0.05 for breast cancer and less than 0.001 for prostate cancer). The range of values was wide. Levels were higher in sclerotic than lytic bone metastases (P less than 0.01) and lower in patients with hypercalcaemia (P less than 0.001). Serial measurements of BGP were made in 53 patients with skeletal metastases from breast cancer receiving systemic therapy. At 1 month BGP rose by greater than 0.5 ng/ml in 15/16 responding patients compared with 7/23 patients with progressive disease (P less than 0.01). Responding patients also showed a rise in the bone isoenzyme of alkaline phosphatase and a paradoxical deterioration in the bone scan appearance, both reflecting a flare in osteoblast activity. The early increase in responding patients was followed by a gradual decrease over subsequent months as the osteoblast reaction induced by systemic therapy subsided. We conclude that BGP measurements reflect a wide variability of bone formation rates in metastatic bone disease. Bone formation was usually increased, particularly when metastases were sclerotic in appearance, but in patients with hypercalcaemia the low BGP levels suggest uncoupling of bone resorption and formation. Serial measurements of BGP may be useful in monitoring response to treatment.
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PMID:Osteocalcin: a potential marker of metastatic bone disease and response to treatment. 326 63


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