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

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 describe the case of a 42-year-old woman diagnosed of chronic renal failure secondary to sarcoidosis. Since the beginning of the dialysis treatment she presented episodes of symptomatic hypercalcemia which did not response to calcium restriction diet and a lower calcium concentration in the dialysate. Secondary hyperparathyroidism and aluminium intoxication were biochemically ruled out. Hypercalcemic crisis were associated to 1.25-dihydroxy-vitamin D (1.25-D) serum levels abnormally raised and they responded quickly to low doses of corticosteroids. Subsequently, this treatment had to be withdrawn because of upper gastrointestinal bleeding, and hypercalcemia recurred. Chloroquine phosphate was prescribed with a rapid response to normalize the serum calcium levels. No side effects was recorded. Twelve months later of chloroquine therapy, the patient remained normocalcemic. A bone biopsy showed an active osteopenia without aluminium deposits, hyperparathyroidism signs or granuloma. We discuss about the pathogenesis of hypercalcemia in this case and its relation with abnormal high serum levels of 1.25-D in hemodialysis patients and sarcoidosis.
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PMID:[Hypercalcemia in a female patient with chronic kidney failure secondary to sarcoidosis: a metabolic study of the calcium metabolism and bone histology]. 205 1

In this brief review of various hypercalcemic disorders and the likelihood of renal calculus formation, it is clearly evident that renal calculi occur much more often in hyperparathyroidism than in the other hypercalcemic states. Dystrophic calcification and nephrocalcinosis are common to all of the hypercalcemic disorders, including hyperparathyroidism, when the hypercalcemia is marked and the limit of solubility of calcium and phosphate in serum is approached. Interestingly, in sarcoidosis there are calcium oxalate crystals in variously distributed sarcoid granuloma, and the renal calculi are composed of calcium oxalate. By contrast, in hyperparathyroidism, the calculi composed of calcium phosphate predominate. This indicates a subtle and as yet undefined alteration in oxalate metabolism in sarcoidosis. An increase in urine pH occurs in hyperparathyroidism, and this enhances formation of crystalline calcium phosphate. However, the striking disparity between the frequency of calculus formation in hyperparathyroidism and that in other hypercalcemic disorders, several of which may be of relatively long duration, suggests that there indeed may be increased promoters of crystal formation in the urine of hyperparathyroid patients.
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PMID:Urinary calculi in hypercalcemic states. 208 14

In the human granulomatous disease sarcoidosis hypercalcemia and/or hypercalciuria result from the endogenous overproduction of 1,25-dihydroxyvitamin D [1,25-(OH)2D] by the disease-activated macrophage. Unlike the renal 25-hydroxy-vitamin D (25OHD)-1-hydroxylase, normally the sole synthetic source of the hormone in man, the 25OHD3-1-hydroxylation reaction in cultured pulmonary alveolar macrophages (PAM) from patients with sarcoidosis is subject to stimulation by the immune cytokine interferon-gamma (IFN gamma) and inhibition by the antiinflammatory glucocorticoid dexamethasone. The data presented here suggest that IFN gamma and calcium ionophore A23187 promote enhanced expression of the sarcoid PAM 25OHD3-1-hydroxylation reaction by increasing endogenous arachidonic acid metabolism through the 5-lipoxygenase pathway. Dexamethasone, an inhibitor of the cellular phospholipase-A2-arachidonic acid-generating system, and BW755C, a lipoxygenase pathway inhibitor, inhibited PAM 1,25-(OH)2D3 synthesis by 64% and 54%, respectively. Conversely, leukotriene C4, a distal metabolite in the arachidonic acid 5-lipoxygenase pathway, increased the hydroxylation reaction by 234% and restored dexamethasone-inhibited PAM 1,25-(OH)2D3 synthetic activity. The results of this study provide presumptive evidence for an important role of agonist (IFN gamma)-calcium-modulated eicosanoid metabolism in the regulated synthesis of 1,25-(OH)2D by PAM in sarcoidosis.
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PMID:A role for endogenous arachidonate metabolites in the regulated expression of the 25-hydroxyvitamin D-1-hydroxylation reaction in cultured alveolar macrophages from patients with sarcoidosis. 210 25

The antifungal drug ketoconazole, a cytochrome P450 inhibitor, has been shown to inhibit renal 1,25-dihydroxyvitamin D production in vitro and to lower serum 1,25-dihydroxyvitamin D levels in normal subjects and in patients with primary hyperparathyroidism. To assess the usefulness of this drug in the hypercalcemia of sarcoidosis, a condition thought to result from overproduction of 1,25-dihydroxyvitamin D by sarcoid-involved tissues, two men with sarcoidosis, hypercalcemia, and elevated serum levels of 1,25-dihydroxy-vitamin D were given ketoconazole, 600-800 mg per day, for four to six days. Serum 1,25-dihydroxyvitamin D levels were markedly reduced (by approximately 40%) in both patients during ketoconazole administration, but serum calcium was not affected. In both patients, renal function deteriorated during ketoconazole treatment. We conclude that ketoconazole administration can lower the elevated serum 1,25-dihydroxyvitamin D levels in sarcoidosis. However, deterioration of renal function during ketoconazole administration as well as failure of hypercalcemia to be affected during short-term ketoconazole treatment suggest that this drug might not be appropriate for acute treatment of hypercalcemic sarcoidosis.
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PMID:Ketoconazole reduces elevated serum levels of 1,25-dihydroxyvitamin D in hypercalcemic sarcoidosis. 216 3

More than a century ago, Jonathan Hutchingson, a surgeon-dermatologist, identified the first case of sarcoidosis at King's College, London. The disease is now known as a commonplace multisystem disorder characterized by the formation of noncaseating granulomata. The diagnosis of sarcoidosis is established by recognizing clinicoradiologic findings and providing histologic evidence of non-caseating granuloma. Serum angiotensin converting enzyme levels are high in about two thirds of the patients and hypercalcemia is a feature in one of every ten victims of sarcoidosis. Immunologic abnormalities include depression of cutaneous delayed-type hypersensitivity, accumulation of T-cells at the site of activity, hyperactive B-cells, and the presence of circulating immune complexes. The course and prognosis of the disease usually correlate with the mode of onset. An acute onset with erythema nodosum indicates a good prognosis and spontaneous resolution; whereas, an insidious onset may be followed by relentless, progressive fibrosis. Mortality and morbidity are caused by pulmonary fibrosis, cardiac arrhythmias, renal failure, neurologic involvement, and blindness. Corticosteroids and chloroquine relieve symptoms and suppress inflammation and granuloma formation.
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PMID:Sarcoidosis. 220 9

Sarcoidosis can affect almost every organ. It has diverse clinical presentations and a variable natural history. Lungs and intrathoracic lymph nodes are the most commonly involved tissues. A major challenge to clinicians is the early identification of those patients with aggressive disease in whom therapy might arrest progression. Although lung uptake of 67Ga citrate, elevated serum angiotensin converting enzyme (ACE) levels and elevated T lymphocyte count in bronchoalveolar lavage fluid are all thought to reflect disease activity, they are by no means reliable markers. Because recent studies have shown that corticosteroid treatment does not avert pulmonary fibrosis and permanent impairment of pulmonary function, the use of these agents is restricted to the palliative treatment of disabling symptoms and physiological derangements. Corticosteroids are effective in reducing ocular inflammation, correcting hypercalcaemia, improving pulmonary function and alleviating symptoms related to hepatic, splenic, articular, myocardial, neural and cutaneous involvement. In the small proportion of patients who do not respond to moderate tolerable doses of steroids, alternative drug therapy such as immunosuppressives or immune modulators must be considered.
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PMID:Current concepts in the management of sarcoidosis. 222 14

Vitamin D in large doses is a proper therapy in hypoparathyroidism, osteomalacia, vitamin D-resistant rickets and also in chronic renal failure although in those cases the active metabolite of vitamin D is preferred because of the much shorter biologic halflife. Apart from these disorders there are no good reasons for using megadoses of vitamin D. Pseudo-vitamin D intoxication is caused by granulomatous diseases as a so-called inappropriate calcitriol secretion. In cases of vitamin D intoxication the 25-OHD3 content in the serum is much too high, the parathyroid hormone concentration is suppressed and the I,25-(OH)2D3 level is low, whereas in pseudo-vitamin D intoxication the 25-OHD3 content in the serum is normal and the I,25-(OH)2D3 is seriously elevated. Cultured alveolar macrophages of patients with sarcoidosis can produce I,25-(OH)2D3 as can sarcoid lymph node homogenate. I,25-(OH)2D3 proved to promote the fusion of alveolar macrophages to form polykaryons. Local concentrations of I,25-(OH)2D3 may be higher at sites of granulomatous tissue and can act in a paracrine or autocrine fashion to enhance granuloma formation. The action of glucocorticoids and chloroquine in patients with sarcoidosis and hypercalcaemia is presumably an interruption of the described vicious circle.
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PMID:[Vitamin D poisoning; real and spurious]. 223 47

A patient with Hodgkin's disease spontaneously developed steroid-responsive hypercalcaemia during two consecutive summers. Administration of 3000 U/day of vitamin D, while he was normocalcaemic, caused a sharp increase in serum 1,25(OH)2D3 (from 59 pg/ml to 142 pg/ml) and subsequently hypercalcaemia while serum 25(OH)D3 rose moderately within the normal range (from 2.8 ng/ml to 10 ng/ml). During a spontaneous episode of hypercalcaemia which was accompanied by increased circulating 1,25(OH)2D3 concentrations, administration of hydrocortisone decreased serum 1,25(OH)2D3 rapidly (from 115 pg/ml to 62 pg/ml) and eventually led to normocalcaemia while serum 25(OH)D3 remained unchanged. Thus the disturbances of mineral metabolism found in this patient with Hodgkin's disease are very similar to those previously described in sarcoidosis.
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PMID:Intermittent hypercalcaemia and vitamin D sensitivity in Hodgkin's disease. 223 11

Circulating immunoreactive intact human parathyroid hormone (PTH) was measured by a direct immunoradiometric assay (IRMA) and the results compared with a radio-immunoassay (RIA) which required extraction and concentration prior to assay. The sensitivity of the IRMA was better than that of the RIA (0.6 vs 2.0 pmol/L). In control subjects the hPTH concentrations ranged between 0.6 and 6.7 pmol/L and in patients with hypercalcaemia due to malignant diseases, sarcoidosis and hypoparathyroidism none could be detected. In patients with primary hyperparathyroidism the concentrations ranged from 5.2 to 27.0 pmol/L. In patients with renal osteodystrophy serum human PTH concentrations ranged from 7.6 to 285 and in those with chronic renal failure but without evidence of renal osteodystrophy from 0.5 to 5.2 pmol/L. The major advantages of the IRMA are its much simpler performance and its higher sensitivity which makes studies of the physiology of PTH secretion in humans possible.
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PMID:Immunoradiometric assay for intact human parathyroid hormone: characteristics, clinical application and comparison with a radio-immunoassay. 231 Jan 59


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