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

Tumours which involve the skeleton do so by producing humoral factors which increase osteoclast and osteoblast activity. Increases in osteoclast activity lead to osteolytic bone destruction and sometimes to hypercalcaemia. Osteolytic metastases are common, and are found most often in patients with lung and breast cancer and in myeloma. The tumour-associated factors responsible are multiple and probably different in each case. Osteoblastic metastases occur most frequently in metastatic cancer of the prostate, and are due to osteoblast stimulating factors released by the tumour cells which have not, as yet, been identified. Agents such as bisphosphonates which inhibit osteoclastic bone resorption are useful in the prevention and treatment of patients with osteolytic metastases, although the precise mechanisms by which these agents work are not yet understood.
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PMID:Mechanisms of osteolytic bone destruction. 195 46

Neoplasia affecting the skeleton is an important cause of morbidity, which includes hypercalcaemia, bone pain and fracture. In most instances these events are mediated by an increase in the resorption of bone which decreases bone density and disrupts skeletal architecture, either at focal sites or generally throughout the skeleton. Neoplastic activation of bone resorption in heterogeneous, but there is now good evidence that this is due to the increased activation of osteoclasts, the cells which mediate bone resorption in health. Bisphosphonates are specific inhibitors of osteoclast-mediated bone resorption and are capable of inhibiting osteoclastic activation independent of the mechanism of its stimulation. This provides the rationale for the use of bisphosphonates in the hypercalcaemia of malignancy. Despite refinements in the use of endocrine therapy, chemotherapy and radiotherapy these interventions have had relatively little impact on the skeletal morbidity or mortality of common malignancies affecting the skeleton, particularly breast cancer and myelomatosis. In addition, there is good evidence that skeletal disease is progressive in many patients despite the use of chemotherapy and radiotherapy. Since accelerated bone resorption can be inhibited by long-term treatment with bisphosphonates, their use is likely to decrease skeletal complications such as bone pain and fracture. The bisphosphonates, therefore, hold great promise as agents to improve the quality of life of such patients.
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PMID:Rationale for the use of bisphosphonates in bone metastases. 195 47

A variety of tumors and nontumorous lesions were used to illustrate some of the biologic, clinical, and pathologic aspects of inappropriate or ectopic endocrine and metabolic syndromes that have musculoskeletal repercussions. It is clear, both from the discussion and case material, that many mechanisms of ectopic endocrine syndromes have yet to be clarified. Elaborate techniques are available for hormonal estimations, but their routine use is prohibitively expensive and relatively unrewarding. Cells of a given lesion may be functionally heterogeneous or may fail to elaborate active products in substantial amounts. Different cells may produce similar peptides, while the same cells can produce more than one. Despite these difficulties, recognition of ectopic endocrine syndromes remains crucial to diagnosis and patient management, and thus corroboration or correlation must often rest on a cruder basis. In fact, the clinical significance of basic laboratory data, e.g., PTH elevation, may vary, as PTH may be immunoreactive but biologically inactive. As another example, hypercalcemia associated with myeloma may be variously related to coexistent hyperparathyroidism, renal disease, dehydration, or humoral osteolysis. Therefore, roentgenographic evidence of bone destruction or skeletal stigmata of hyperparathyroidism imbues laboratory data with greater significance. Paraneoplastic syndromes are of particular concern to the radiologist, as multiple systemic manifestations, occurring either synchronously or metachronously, may suggest the presence of an underlying or unifying lesion or even of a specific type of neoplasm. They may precede detection of neoplasms by months to years and can develop at any time during their course. Paraneoplastic syndromes may, furthermore, parallel the course of a lesion and be used as indicators of remission or recurrence. Conversely, those unassociated with overt symptoms possess endocrine markers that can reinforce sometimes silent skeletal stigmata. Familiarity with representative secretory products influencing the musculoskeletal system per se may often clarify seemingly innocuous and sometimes asymptomatic skeletal findings. Alert imagers may, therefore, detect, infer, or suspect particular syndromes when they present in a specific sequence or mosaic. Conversely, when apprised of their existence, imagers should know where their related effects may be sought or anticipated. Such relationships, sometimes serendipitously discovered, may be valuable assets in clinical diagnosis and patient management in both suspected and unsuspected cases.
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PMID:Skeletal manifestations of ectopic or inappropriate endocrine and metabolic syndromes. 198 23

The pretreatment characteristics of 265 multiple myeloma patients treated between 1977 and 1983 were evaluated as potential prognostic factors for survival. Patients whose diagnosis was based on bone marrow plasmacytosis (greater than 30%) were noticed to have poorer survival (P less than 0.001). Although classification of patients according to stage has traditionally been used to identify prognostic groups, differences in survival were noted only between Stage III and Stage I or II patients using one of two common staging systems. Multivariate analysis using Cox's proportional hazards model identified the following prognostic factors in order of importance: plasmacytosis (hazard ratio [HR] = 2.2, 95% confidence interval [CI] = 1.49 to 3.27), hypercalcemia (HR = 1.68, CI = 1.22 to 2.32), hypoalbuminemia (HR = 1.51, CI = 1.15 to 1.99), alkaline phosphatase (HR = 1.62, CI = 1.18 to 2.23), hyperuricemia (HR = 1.46, CI = 1.09 to 1.96), and renal insufficiency (HR = 1.48, CI = 1.08 to 2.04). All patients were followed from 2 to 7.5 years and 130 (49%) survived over 2 years. Logistic regression analysis demonstrated that hyperuricemia, hypoalbuminemia, renal insufficiency, plasmacytosis, gender, alkaline phosphatase, and hypercalcemia were significant predictors of 2-year survival. Knowledge of these factors could be of value in predicting prognosis and planning therapy in patients with multiple myeloma.
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PMID:Prognostic factors in multiple myeloma. 204 58

Tubular reabsorption of calcium (Ca) is becoming recognized as a determinant of malignant hypercalcemia. However, its importance as compared to increased bone resorption has not yet been widely investigated. We determined Ca fluxes of bone resorption and tubular reabsorption in 141 rehydrated patients with hypercalcemia of malignant or benign origin, before any specific treatment. Bone resorption (BRI) was evaluated by fasting urinary Ca excretion and Ca tubular reabsorption using an index (TRCaI) calculated from a nomogram relating fasting urinary Ca excretion and calcemia. The relationship between alterations in TRCaI and in the tubular capacity to reabsorb inorganic phosphate (Pi), as judged by TmPi/GFR, was also examined for each cause of hypercalcemia. Among 101 cases with malignancy, 67% had overt bone metastases, but all displayed increased BRI. Calcemia was highest in breast cancer and lowest in prostate carcinoma. BRI was markedly increased in breast cancer, lymphoma, and multiple myeloma, whereas it was slightly elevated in lung squamous cell, renal, and liver carcinomas. TRCaI was increased in 49% of malignant hypercalcemia, particularly in epidermoid (above the upper normal limit in 71% of the cases), renal, and liver carcinomas. It was elevated in 54% of breast cancer and normal in multiple myeloma and prostate cancer. In nonmalignant hypercalcemia, BRI was markedly increased in vitamin D intoxication, sarcoidosis, and immobilization. In primary hyperparathyroidism (PHP), BRI was moderately increased. TRCaI was abnormally elevated in PHP, but normal in vitamin D intoxication, sarcoidosis, and immobilization. In malignant hypercalcemia, TmPi/GFR was low in 77% of patients and in all types of tumors, except in prostate carcinoma. The index ratio [TRCaI/(TmPi/GFR)] gave a better discrimination of PHP from other causes of nonmalignant hypercalcemia than the use of either TRCaI or TmPi/GFR taken alone. Thus, in malignant hypercalcemia, increased bone resorption is associated with an elevation in tubular Ca reabsorption in half the patients surveyed, whereas low tubular Pi reabsorption is observed in more than 75%. Increased TRCaI is restricted to some types of tumor, whereas decreased TmPi/GFR is observed in all types except prostate carcinoma. In nonmalignant hypercalcemia, a significant increase in mean TRCaI was only observed in PHP, of which individual cases can be fully discriminated from other conditions by using a new index taking into account alteration in the renal transport capacity of both Ca and Pi.
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PMID:Evaluation of bone resorption and renal tubular reabsorption of calcium and phosphate in malignant and nonmalignant hypercalcemia. 205 36

We selected 37 cases, followed-up for more than 36 months or until death, from a series of 45 patients affected by acute renal failure due to multiple myeloma in order to identify the parameters that could allow the outcome to be predicted. The patients were allocated to group 1, consisting of 27 patients who died within one year and to group 2, consisting of 10 patients who survived for more than 36 months. Renal failure was severe enough to require dialysis in 28 patients, 16 of whom were oliguric. Renal biopsy was performed in 23 cases, whereas light chain isoelectric point and serum beta 2-microglobulin levels were evaluated in each patient. All the patients underwent chemotherapy, which was associated with plasma exchange in 16 patients. Statistical analysis of the potential prognostic factors in the 2 groups showed that the incidence of hypercalcemia, infection, irreversible renal failure and severe tubulo-interstitial damage was significantly higher in group 1. Sex, tumor load, severity of renal failure and light chain isoelectric point had no prognostic significance. Finally, the number of patients treated by plasma exchange was significantly higher in group 2. Our results underline the prognostic role of both hypercalcemia and infection and justify aggressive treatment consisting of chemotherapy, plasma exchange and dialysis, even in cases of severe renal failure and high tumor load.
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PMID:Long-term survival patients with acute and severe renal failure due to multiple myeloma. 207 67

The performed clinical analysis covered 80 patients with multiple myeloma, treated at Hematological Clinic of PMA in the years from 1974 to 1984. The following prognostic factors were analyzed: age, sex, living place, clinical advancement period of the disease, functional state according to Karnofsky (Karnofsky's index), monoclonal protein type, the concentration of urea, creatinine, calcium in blood serum, hemoglobin concentration as well as the neoplastic tumour mass. These factors were considered to indicate poor prognosis: severe anemia, hypercalcemia, renal failure, and Karnofsky's index being below 70 points.
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PMID:[Retrospective analysis of patients with multiple myeloma; clinical characteristics and prognostic factors]. 209 6

When bone-marrow cells from patients with multiple myeloma (MM) were seeded in short-term cultures, a spontaneous proliferation of the myeloma cells occurred for most of the patients with active disease and proliferating myeloma cells in vivo. In all cases, this spontaneous proliferation was inhibited by anti-IL-6 monoclonal antibodies (mabs). Moreover, myeloma cell lines, completely dependent upon exogenous IL-6 for their growth, could be reproducibly established by initially stimulating the myeloma cells with both IL-6 and GM-CSF. These results demonstrate that IL-6 is a major paracrine myeloma-cell growth factor in vitro. High serum IL-6 levels were observed in MM patients with active disease, especially patients with terminal disease. High IL-6 mRNA levels were found in bone-marrow cells of MM patients, mainly in myeloid and monocytic cells, in vivo. The myeloma cells did not express IL-6 mRNA. Injection of anti-IL-6 mabs to MM patients with terminal disease and extramedullary proliferation, completely blocked the myeloma-cell proliferation in vivo and completely inhibited the serum IL-6 bioactivity and the serum CRP levels. One patient with plasma cell leukemia and hypercalcemia was treated for two months with anti-IL-6 mabs and maintain in remission for 2 months without major side effects. Interestingly, the serum calcium levels also decreased in these patients. All these results show that IL-6 is the main cytokine responsible not only for the myeloma-cell proliferation in vivo, but presumably also for the large bone resorption processes observed in human MM.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interleukin-6 is the central tumor growth factor in vitro and in vivo in multiple myeloma. 210 41

Hypercalcemia occurs for various reasons in patients with malignant diseases. Most of these patients show a relative increase in bone resorption over bone formation. Increased renal tubular calcium reabsorption is also important for maintaining hypercalcemia in the majority of patients. Calcium absorption from the gut is usually decreased. In a few patients, fixed impairment of glomerular filtration contributes to hypercalcemia. Because the pathophysiology of hypercalcemia is heterogeneous, it may be considered as three separate syndromes: the humoral hypercalcemia of malignancy caused by systemic mediators; the hypercalcemia associated with localized osteolytic disease; and the hypercalcemia associated with myeloma and related hematologic malignancies. Increased bone resorption is a key feature in each of these syndromes. In malignant disease, bone resorption is enhanced because osteoclast activity is increased by the production of humoral mediators. These mediators are often produced by the tumor cells but are also produced by normal host cells that have been activated by the presence of the tumor. some of these mediators of hypercalcemia are systemic factors, but some act only locally. They include parathyroid hormone-related protein, transforming growth factor alpha, lymphotoxin, tumor necrosis factor, interleukin-1 alpha and 1,25-dihydroxyvitamin D.
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PMID:Incidence and pathophysiology of hypercalcemia. 210 29

Monoclonal immunoglobulin deposition occurs in tissues as Congo Red binding fibrils in light chain amyloidosis, as less structured deposits in light chain deposition disease, and as similar but distinct deposits in light and heavy chain deposition disease. The nonamyloid forms were found in 13 patients who had evidence of plasmacytic dyscrasia by the immunohistochemical detection of immunoglobulin light chains of kappa or lambda class (with or without staining for a single heavy chain isotype) and by the absence of amyloid P component in tissue sections that did not show the birefringence characteristic of amyloid after Congo Red staining. All but two of the patients presented with proteinuria with or without azotemia. Clinical syndromes involving other organ systems were less common but occasionally severe. Four patients had overt multiple myeloma. Three others had hypercalcemia and mild bone marrow plasmacytosis but no lytic lesions. Analyses of immunoglobulin synthesis in bone marrow cells from seven patients showed excess light chains in all and incomplete light chains or heavy chain fragments in six, regardless of whether an intact monoclonal protein or related subunit was in the serum or urine. The fibrillar (amyloidotic) and nonfibrillar forms of monoclonal immunoglobulin deposition occur either in overt multiple myeloma or in the course of less neoplastically aggressive plasmacytic dyscrasias. Bone marrow cells from patients with either type produce immunoglobulin fragments that are related to those deposited in the affected tissues.
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PMID:Monoclonal immunoglobulin deposition disease: light chain and light and heavy chain deposition diseases and their relation to light chain amyloidosis. Clinical features, immunopathology, and molecular analysis. 210 17


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