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)

1,25-Dihydroxyvitamin D3, [1,25(OH)2D3], the biologically most active metabolite of vitamin D3, is involved in the regulation of calcium homeostasis and bone metabolism. Recently, receptors for 1,25(OH)2D3 have also been shown in cells and tissues not directly related to calcium homeostasis. Experimental data obtained with leukaemic and cancer cell lines, both in vitro and in vivo, showed the effects of 1,25(OH)2D3 on cell differentiation and proliferation. However, high doses of the sterol have to be used to observe these effects. Additional studies are needed to establish whether 1,25(OH)2D3 or suitable analogues have a therapeutic potential in malignant diseases without unacceptable toxicity like the development of hypercalcemia.
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PMID:Vitamin D: a modulator of cell proliferation and differentiation. 228

In order to assess the long-term effects of calcitriol treatment in postmenopausal osteoporotic patients, 1.0 micrograms/d of calcitriol was administered in two divided doses for 1 to 8 years to 270 women with symptomatic, histologically proven postmenopausal osteoporosis. No calcium supplementation was given. Clinically, the treatment resulted in substantial relief from pain, with improvement of ambulancy. Intestinal calcium absorption, which was lower than normal at baseline, increased significantly and remained higher than the baseline value as long as calcitriol was administered. Urinary calcium absorption also increased, but hypercalcemia occurred, exceptionally and transiently, in only a few patients. Urinary hydroxyproline excretion did not increase, indicating that hypercalciuria was not of resorptive origin. Total-body density, determined by dual-photon total-body absorptiometry in 56 patients, showed an increase after 18 to 24 months of therapy in most cases. The occurrence of nontraumatic, clinically relevant fractures decreased noticeably as compared with the period preceding calcitriol treatment. No change occurred in renal function, and no renal stones developed. Calcitriol was an effective and safe treatment of postmenopausal osteoporosis.
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PMID:Long-term treatment with calcitriol in postmenopausal osteoporosis. 232 71

We treated a hypoparathyroid woman with calcitriol during pregnancy and did not reduce the dosage after delivery. Despite lactation, the serum calcium level increased to 15.4 mg/dL 11 days postpartum. We treated two other hypoparathyroid women during four pregnancies with either calcitriol or dihydrotachysterol. In all five pregnancies, requirements for the vitamin D preparations increased beginning at the 20-28th week of gestation. Hypercalcemia did not occur in the two women who did not breast-feed and in whom we reduced the dose of calcitriol or dihydrotachysterol after delivery. We conclude the following: 1) Calcitriol is effective for treating hypoparathyroidism during pregnancy; 2) the dose usually needs to be increased during the latter half of gestation; 3) the calcitriol dose should be reduced during lactation; and 4) both mother and infant should be monitored to detect hypercalcemia during breast-feeding. We speculate that low serum estrogen levels associated with breast-feeding promote bone resorption and diminish calcitriol needs in lactating hypoparathyroid women.
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PMID:Hypercalcemia in a calcitriol-treated hypoparathyroid woman during lactation. 238 32

Phosphorus is a well-known modulator of renal 1 alpha-hydroxylase activity. In early and moderate renal failure it is proposed that dietary Pi reduction ameliorates secondary hyperparathyroidism through increased circulating levels of calcitriol (i.e, 1 alpha, 25-dihydroxycholecalciferol). To gain further insight into the mechanisms by which a low-Pi diet ameliorates secondary hyperparathyroidism in advanced renal insufficiency, studies were performed in five dogs before and 6 mo after the induction of uremia by 5/6 nephrectomy. Glomerular filtration rate decreased from 69.0 +/- 2.3 to 10.5 +/- 0.5 ml/min, immunoreactive parathyroid hormone (irPTH) increased from 66.0 +/- 8.8 to 321.0 +/- 46 pg/ml, and calcitriol decreased from 39.0 +/- 10.4 to 27.0 +/- 6.2 pg/ml. Thereafter, dietary Pi was decreased gradually every 2 wk from 0.95% to 0.6, 0.45, and 0.3%, respectively. Dietary Ca was reduced from 1.6 to 0.6% to prevent development of hypercalcemia. Ionized Ca (ICa) decreased from 5.4 +/- 0.04 to 5.2 +/- 0.05 mg/dl (P less than 0.02), and plasma Pi decreased from 6.3 +/- 0.7 to 4.7 +/- 0.2 mg/dl (P less than 0.05). Calcitriol remained low (23.3 +/- 4.7 pg/ml). However, irPTH gradually decreased from 321.0 +/- 46.0 to 94.7 +/- 22.9 pg/ml (P less than 0.005). These studies indicate that a decrease in dietary Pi from 0.95 to 0.3% suppressed irPTH by approximately 70%. Reduction of irPTH was observed in the absence of a concomitant increase in levels of ICa or calcitriol. These studies suggest that reduction in dietary Pi in advanced renal insufficiency improves secondary hyperparathyroidism by a mechanism that is independent of the levels of calcitriol or plasma ICa.
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PMID:Phosphorus restriction reverses hyperparathyroidism in uremia independent of changes in calcium and calcitriol. 239 69

We studied the effects of intravenous calcitriol in four persistently hypercalcaemic patients established on haemodialysis. All had marked hyperparathyroidism and had been previously shown to be intolerant to vitamin D by mouth. Calcitriol was administered at the end of each dialysis session in doses of 0.5-2.5 micrograms for 2 months and continued for 7 and 8 months in two patients. A significant decrease in serum calcium was observed after 2 weeks, which was maintained throughout treatment despite increasing the dose of calcitriol. This was associated with a decrease in serum concentrations of iPTH (28% of the initial value at 4 weeks), suggesting a shift in the set-point for PTH secretion. During longer-term treatment, serum calcium values increased, but lower concentrations of iPTH were maintained. We conclude that an increment in serum calcium is not a prerequisite for the suppressive action of calcitriol on parathyroid secretion and that the presence of hypercalcaemia does not preclude its use. Longer-term studies on a larger number of patients are required to assess the therapeutic potential of intravenous calcitriol in hypercalcaemic patients.
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PMID:Intravenous calcitriol lowers serum calcium concentrations in uraemic patients with severe hyperparathyroidism and hypercalcaemia. 250 76

In an open, controlled study 34 patients with tumor hypercalcemia of different origin were treated with clodronate. The initial dosage was 300 mg intravenously daily. After achieving normocalcemia, treatment was continued orally using 400-3200 mg/day depending on serum calcium concentration. Most patients showed normocalcemia within 1 week of treatment - only few of them needed a longer time. Fifteen of 34 patients died within the observation time of up to 24 weeks, some being normocalcemic. However, a reincrease in plasma calcium during treatment was an indicator of deterioration. Measurements of plasma parathyroid hormone (PTH) using an intact molecule radioimmunometric assay showed depressed levels before clodronate treatment started, but PTH rose after achieving normal and especially low normal calcium levels. Starting 1,25-dihydroxycholecalciferol [1,25(OH)2D3] values were decreased or in the lower normal range in the majority of patients, but in 6/21 patients plasma 1,25(OH)2D3 was in the upper normal range or elevated despite hypercalcemia. After lowering plasma calcium the 1,25(OH)2D3 levels increased. However, there was no significant correlation between PTH and 1,25(OH)2D3. Therefore we assume that in some patients additional stimulation of renal 1 alpha-hydroxylase by tumor products is present.
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PMID:Treatment of tumor hypercalcemia with clodronate. 252

1,25-Dihydroxyvitamin D (1,25-(OH)2D3) directly suppresses the secretion and synthesis of PTH in vivo and in cell culture. This compound has been used to treat secondary hyperparathyroidism associated with renal failure, but in some patients prolonged treatment with 1,25-(OH)2D3 results in hypercalcemia. An analogue of 1,25-(OH)2D3 with little or no calcemic activity, 22-oxacalcitriol (OCT), was recently developed. We confirmed this lack of calcemic activity by acute and chronic administration to normal rats. A single intraperitoneal injection of vehicle (propylene glycol), OCT, or 1,25-(OH)2D3 (1.0 micrograms/rat) increased calcium by 0.32, 0.30, and 1.40 mg/dl, respectively. When rats were given daily injections of vehicle or 0.5 micrograms of either 1,25-(OH)2D3 or OCT for 4 d, calcium did not change in the rats receiving vehicle or OCT, but increased from 8.4 to 11.4 mg/dl in the rats treated with 1,25-(OH)2D3. In primary cultures of bovine parathyroid cells, 10 nM OCT was as active as 10 nM 1,25-(OH)2D3, suppressing PTH release by 33%. This suppression is due, at least in part, to blocking of transcription of the PTH gene. Using a probe prepared by random prime labeling of an Msp I fragment of plasmid PTHm122, we found that a single 40-ng dose of OCT or 1,25-(OH)2D3 depressed PTH mRNA levels by 70-80% by 48 h when compared with vehicle. Thus, OCT is a very effective suppressor of PTH secretion with virtually no calcemic activity. This analogue may be a valuable tool for the treatment of secondary hyperparathyroidism.
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PMID:The noncalcemic analogue of vitamin D, 22-oxacalcitriol, suppresses parathyroid hormone synthesis and secretion. 276 Feb 11

Clinical investigations have shown that 1 alpha-hydroxycholecalciferol (oxydevit, alphacalcidiol) and 1 alpha, 25-dihydroxycholecalciferol (rocaltrol) are act vitamin D3 agents producing a positive clinical effect in different types of osteoporosis and osteomalacia. Clinical improvement of the patients' status (alleviation of the pain syndrome, an increase in motor activity) was noted in 1-2 mos., an x-ray picture of regeneration of the bone structure of both axial and peripheral skeleton--in 6-12 mos. after the initiation of therapy. Therapy was attended by an increase in the serum content of total and ionized calcium, the return of alkaline phosphatase activity to normal, and a decrease in the level of parathormone. During prolonged therapy these agents administered at daily doses of 0.25-2 micrograms caused no pathological side-effects and hypercalcemia. In osteoporotic conditions all these drugs were equal in their clinical effectiveness. Rocaltrol has some advantages in the presence of associated liver pathology.
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PMID:[Comparative evaluation of the effectiveness of vitamin D3 preparations (1-alpha-hydroxy- and 1-alpha,25-dihydroxycholecalciferol in various forms of osteoporosis and osteomalacia]. 276 60

Five patients with symptomatic osteomalacia undergoing chronic hemodialysis took 24R,25-dihydroxycholecalciferol, 10 micrograms/day, for periods of 6-20 months. Four patients took calcitriol simultaneously in doses consistent with normocalcemia, but the 5th was unable to do so because of recurrent hypercalcemia. In the group as a whole, despite achievement of physiologic plasma concentrations of 24,25-dihydroxyvitamin D, we could demonstrate no metabolic or histologic benefit of therapy. Substantial osteomalacia persisted in all posttreatment biopsy specimens, appearing more severe in some cases and less severe in others. At the doses prescribed, the results of treatment of dialysis osteomalacia with 24R,25-dihydroxycholecalciferol were clinically unsatisfactory.
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PMID:Persistence of dialysis osteomalacia despite treatment with 24R,25-dihydroxycholecalciferol. 278 66

Renal ultrasonography was performed on 23 patients with X-linked hypophosphatemic rickets (XLH) and 11 patients with autosomal recessive vitamin D-dependent rickets (ARVDD). A pattern of increased echogenicity of the renal pyramids (ERP) was identified in 11/23 patients with XLH and 3/11 patients with ARVDD; this ultrasonographic finding has previously been associated with medullary nephrocalcinosis. Patients with XLH and ERP had significantly higher mean serum calcium and phosphate concentrations, more frequent episodes of hypercalcemia, and higher doses of oral vitamin D and phosphate during the first 3 years of therapy. Episodes of hypercalcemia were more frequent when patients received higher doses of vitamin D2 (greater than 4000 IU/kg/day) or 1,25-dihydroxycholecalciferol (greater than 40 ng/kg/day). Episodes of hypercalciuria were significantly increased at doses of greater than 20 ng/kg/day 1,25-dihydroxycholecalciferol. In patients with ARVDD, ERP was also correlated with vitamin D dose and frequency of hypercalcemia episodes. ERP was not associated with an elevation of serum creatinine or loss of urinary concentrating ability in either patient group.
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PMID:Nephrocalcinosis and its relationship to treatment of hereditary rickets. 282 87


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