Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020438 (hypercalciuria)
 2,502 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Variants of renal damage in sarcoidosis demonstrate the diversity of clinical manifestations common to this systemic disease and serve distinctive reference points in the choice of the treatment policy. A well-defined relationship between hypercalciuria associated with sarcoidosis and risk of calcium nephropathy development is, one the one hand, a reliable criterion for the disease activity and, on the other one, the basis for administration of drug the therapy permitting one to control its level (corticosteroids and drugs of the 4-aminoquinoline series). Other variants of renal damage in sarcoidosis, excluding amyloidosis, form the basis for corticosteroid administration even in cases of the presence of renal failure, demonstrating that so-called "dramatic therapy" produces a remarkable beneficial effect characterized by the disappearance of the signs of renal failure.
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PMID:[Kidney involvement in sarcoidosis]. 194 30

A 47-year-old patient presented with hypercalcemia secondary to sarcoidosis and was successfully treated with 1 year of corticosteroids leading to improvement in his hypercalcemia, hypercalcuria, and elevated levels of 1,25-dihydroxyvitamin D. Angiotensin-converting enzyme levels (ACE) normalized and serum creatinine improved. When hypercalcemia recurred after a 3-year symptom-free interval, the patient refused repeat corticosteroid treatment and was placed on ketoconazole (initially 600 and eventually 800 mg/d). Ketoconazole controlled the patient's hypercalcemia (serum calcium, 3.2 to 2.6 mmol/L [12.8 to 10.4 mg/dL]), but only the larger dose suppressed serum 1,25-dihydroxyvitamin D levels into the normal range. Hypercalcuria was markedly improved with ketoconazole, decreasing from a peak of 23 mmol/d (940 mg/d) to less than 8.7 mmol/d (350 mg/d) on a dose of 800 mg. However, serum ACE levels remained elevated on ketoconazole. An attempt to taper the ketoconazole after 1 year resulted in rapid recurrence of hypercalcemia (serum calcium, 2.8 mmol/L [11.1 mg/dL]) and hypercalcuria (urinary calcium excretion, 11 mmol/d [451 mg/d]). After a total of 2 years of ketoconazole treatment, his defect in calcium metabolism remains well controlled despite persistent elevation in ACE levels. Serum cortisol levels and liver function tests remain normal on therapy, although there has been a slight decrease in serum testosterone levels accompanied by some decrease in libido. These data suggest that long-term use of ketoconazole may be a safe and effective alternative to corticosteroid treatment for sarcoid-associated hypercalcemia. Further study is needed to determine whether the long-term side effects of ketoconazole therapy or its failure to control disease activity in sarcoidosis outweigh its advantages in avoiding the known side effects of glucocorticoids.
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PMID:Treatment of sarcoidosis-associated hypercalcemia with ketoconazole. 196 57

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

We report results for adjusted ionized calcium (at pH 7.4) and actual ionized calcium (at actual pH) in capillary blood from 183 patients with disorders of calcium metabolism (primary hyperparathyroidism, secondary hyperparathyroidism of malabsorption, primary hypoparathyroidism, Paget's disease, acromegaly, hypercalcemia of malignancy, osteoporosis, sarcoidosis, idiopathic hypercalciuria, and familial hypocalciuric hypercalcemia). The correlation and the equation for the linear regression between adjusted ionized calcium (y) and actual ionized calcium (x) were y = 1.011x + 0.005 mmol/L, r = 0.992, Sy,x = 0.021 mmol/L. Results were similar within each diagnostic group. Consistent agreement between adjusted and ionized calcium was observed in 96.7% of patients representing a variety of the most frequently encountered disorders of calcium metabolism. Thus we find adjusted ionized calcium to be as useful as actual ionized calcium for evaluation of patients with such disorders. Adjusted ionized calcium may therefore also be a logical choice for establishing agreement between laboratories for reference intervals in healthy adults.
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PMID:Adjusted ionized calcium (at pH 7.4) and actual ionized calcium (at actual pH) in capillary blood compared for clinical evaluation of patients with disorders of calcium metabolism. 231 Dec 30

One hundred and twenty-five cases of biopsy proven sarcoidosis have been found during a prospective study since 1972 in Calcutta, Eastern India. The presentation, clinical course and radiological features are considerably different from those seen in the West. Elderly males over 40 years are more prone. Low grade fever, cough, dyspnoea, arthralgia are common symptoms while hepatosplenomegaly, hypercalcaemia, hypercalciuria and hyperglobulinaemia are frequent signs. Nearly 60% are MT negative (up to 100 TU). Serum angiotensin converting enzyme and high lymphocyte count in bronchoalveolar lavage fluid are usual findings in active disease. Chest X-ray usually shows mottled opacities or fibrosis in 60% cases. Clinico-radiological dissociation (i.e. remarkable dissociation between the alarming-looking chest X-ray and scanty physical signs and symptoms in chest) was a very remarkable feature in this series. Treatment with oral steroid or steroid aerosol with oxyphenbutazone and chloroquine give equally good results initially. However, most cases tend to relapse inspite of adequate initial treatment. The pattern of the disease is similar almost all over India with minor regional differences like more erythema nodosum and eye involvement in Chandigarh in the extreme north (which could also have been due to case selection). The pattern from Northern India (Delhi) and Western India is nearly similar to our figures.
Sarcoidosis 1990 Mar
PMID:Sarcoidosis in India: a review of 125 biopsy-proven cases from eastern India. 234 18

Idiopathic hypercalciuria, defined as the urinary excretion of more than 300 mg. calcium per day in men or more than 250 mg. calcium per day in women, or more than 4 mg. calcium per kg. per day, is observed in about 50 per cent of the patients with calcium oxalate/apatite nephrolithiasis and is one of the risk factors for stone formation. These patients do not exhibit hypercalcemia, elevated serum parathyroid hormone concentrations or urinary cyclic adenosine monophosphate excretion nor clinical evidence of sarcoidosis, other granulomas or a malignancy. Hypophosphatemia may be present. Augmented rates of intestinal absorption of dietary calcium account for most of the increments in urinary calcium. Serum 1,25-dihydroxyvitamin D concentrations are in the upper normal range or elevated among many patients and are normal but not suppressed in the others. Activation of 1,25-dihydroxyvitamin D formation may be secondary to hypophosphatemia or other, as yet undefined, factors. Since, 1,25-dihydroxyvitamin D apparently can up-regulate its own receptor, small increments in its synthesis and blood levels could amplify the effect of the hormone to stimulate intestinal calcium absorption. Calcium balances are slightly but significantly negative and urinary hydroxyproline excretion may be increased so that a generalized disorder of calcium homeostasis also involving bone may be present. Additional studies are required to determine the genetic basis for the occurrence of idiopathic hypercalciuria in families, the cause of greater expression of idiopathic hypercalciuria in men and whether environmental factors (high dietary sodium chloride, protein and purified carbohydrate intakes) contribute to the expression of idiopathic hypercalciuria. Although thiazide diuretics, inorganic phosphate, magnesium hydroxide and potassium citrate have provided effective therapy, prospective studies are needed to determine optimum therapy and the optimum duration of treatment.
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PMID:Idiopathic hypercalciuria. 264 29

The endogenous overproduction of active vitamin D sterols plays a central causative role in the hypercalcemic/hypercalciuric state associated with granuloma-forming diseases, most notably sarcoidosis, as well as with some human lymphomas. In sarcoidosis, the offending metabolite is most likely 1,25-(OH)2-D and the synthetic source is the disease-activated macrophage. About 50% of hypercalcemic patients with lymphoma harbor frankly elevated or inappropriately high serum 1,25-(OH)2-D concentrations. The source of the hormone in patients with lymphoma is not yet known. The endogenous synthesis of 1,25-(OH)2-D in patients with active sarcoidosis and lymphoma is not subject to regulation by those factors that normally control the production of 1,25-(OH)2-D by the renal 25-OH-D-1-hydroxylase. Treatment and prevention of vitamin D metabolite-mediated hypercalcemia/hypercalciuria consist of pharmacologic inhibition of the abnormal 1-hydroxylation reaction and limitation of substrates for the reaction. The former is best accomplished by the administration of anti-inflammatory concentrations of glucocorticoids and the latter by controlling vitamin D intake and sunlight exposure in susceptible hosts.
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PMID:Vitamin D metabolite-mediated hypercalcemia. 267 72

In normal individuals, 1,25-dihydroxyvitamin D (1,25-D) levels regulate calcium (Ca) absorption according to Ca intake; its synthesis is stimulated by low Ca intake, probably via increased parathyroid hormone (PTH) secretion, to increase Ca absorption, and suppressed during high intake to reduce Ca absorption. The body also adapts Ca absorption in response to renal Ca excretion, and phosphate absorption in response to phosphate intake. These adaptations may fail or be impaired in certain diseases. In disorders of overadaptation, the intestinal tract absorbs excessive amounts of Ca due to overproduction of 1,25-D, as in absorptive hypercalciuria, sarcoidosis, primary hyperparathyroidism, and tumoral calcinosis. Intestinal hyperabsorption and hypercalciuria may occur on both low- and high-Ca diets. Primary hyperparathyroidism and hypoparathyroidism are bihormonal, related to over- and underproduction, respectively, of both 1,25-D and PTH. Underadaptation disorders are typically related to low 1,25-D synthesis or resistance to this metabolite; examples include postmenopausal osteoporosis, chronic renal failure, and osteomalacia. Many of these adaptational disorders can be relieved or improved by manipulating Ca, phosphate, sodium, or protein intake or by administering exogenous 1,25-D. Overabsorption of Ca and other substances, such as oxalate, may be responsible for Ca nephrolithiasis. Hypocitraturia (which may be a complication of certain diseases or the result of unbalanced diet or excessive exercise), diets high in readily metabolizable sugars and purine-rich proteins (meat, poultry, and fish), and low fluid intake can all contribute to stone formation. Various regimens may reduce the risk of Ca nephrolithiasis.
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PMID:Calcium metabolism. 268 27

The "syndrome of inappropriate calcitriol secretion" may be observed in diseases with disseminated granulomas. The main examples are sarcoidosis and tuberculosis, but it can also be observed in fungal infections, in granulomas due to foreign bodies and in lymphomas. The syndrome is due to autonomous production of 1 alpha hydroxylase by granulomas. The insuing synthesis of calcitriol escapes normal regulation by serum calcium and phosphate levels. The syndrome includes hypercalcemia, hypercalciuria, high 1,25(OH)2D3 serum levels and reduced PTH secretion. It can supervene in anephric or hypoparathyroid patients. The notion that calcitriol may be secreted extrarenally is new. It could have important bearings on several issues in nephrology, immunology and oncology.
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PMID:[Inappropriate calcitriol secretion syndrome]. 295 94

Hypercalcemia and hypercalciuria in sarcoidosis are thought to result from the endogenous overproduction of an active vitamin D metabolite. We employed primary cultures of pulmonary alveolar macrophages from two patients with biopsy-proven pulmonary sarcoidosis and a recent or current clinical abnormality in calcium metabolism to synthesize in vitro a 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]-like metabolite from 25-hydroxyvitamin D3 (25OHD3). The macrophage metabolite cochromatographed with [3H]1,25-(OH)2D3 on normal phase and reverse phase high performance liquid chromatography and was bound with high affinity by the chick intestinal receptor for 1,25-(OH)2D3. On UV spectroscopy, the metabolite possessed the carbon-5,7,10 (19) cis-triene chromophore characteristic of a vitamin D sterol. Electron impact mass spectrometry of trimethylsilyl ether derivatives of the metabolite revealed a mass fragmentation pattern similar to that of the trimethylsilyl ether derivative of authentic 1,25-(OH)2D3. The incubation of cultured macrophages from two patients with idiopathic pulmonary fibrosis and two with scleroderma with [3H]25OHD3 did not result in production of a metabolite with the chromatographic identity of 1,25-(OH)2D3. These data indicate that the metabolite of 25OHD3 synthesized by sarcoid macrophages in vitro is 1,25-(OH)2D3 and that the macrophage is a synthetic source of the sterol metabolite in sarcoidosis.
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PMID:Isolation and structural identification of 1,25-dihydroxyvitamin D3 produced by cultured alveolar macrophages in sarcoidosis. 298 38


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