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)

Humoral hypercalcemia of malignancy (HHM) is at least partly caused by tumor secretion of PTH-related peptide (PTHrP), but there is growing evidence for cosecretion with PTHrP of other bone-resorbing peptides, such as the cytokine interleukin-1 alpha (IL-1 alpha). Administration of PTHrP in vivo and in vitro generally mimics the actions of PTH itself, with increases in both resorption and formation of bone. However, bone in HHM is characterized by uncoupling of bone turnover, with increased resorption and decreased formation. We performed experiments to determine whether IL-1 alpha might alter the effects of PTHrP and produce uncoupling. Thus, we administered to 100-g male rats by sc osmotic minipumps synthetic PTHrP-(1-34) alone (2 micrograms/100 g/day), recombinant IL-1 alpha alone (1.5 micrograms/100 g/day), both peptides together at the previous doses, or vehicle only. We infused 5 groups of 12 rats each (PTHrP, IL-1 alpha, PTHrP plus IL-1 alpha, ad libitum fed control, and controls pair-fed to the PTHrP plus IL-1 alpha group) for 14 days. At the end of the study, blood and urine were taken for chemical measurements, and tibias and femurs were harvested for histomorphometry and extraction of RNA from periosteal cells. As expected, PTHrP induced hypercalcemia, relative hypophosphatemia, phosphaturia, and reduced bone mass. Osteoblast number was increased, but osteoclast number was not. Indices of bone formation were unchanged or reduced. The dose of IL-1 alpha chosen had no statistically significant effect, except for reduced longitudinal bone growth, but when combined with PTHrP, IL-1 alpha reduced hypercalcemia, hypophosphatemia, and phosphaturia. In contrast to the blood and urine effects, IL-1 alpha did not interact significantly with PTHrP's effect on bone measurements. Northern analysis of periosteal cell mRNA showed that PTHrP reduced expression of osteocalcin, but not glyceraldehyde-3-phosphate dehydrogenase; IL-1 alpha had no additional effect. These data suggest that 1) continuously administered PTHrP alone may induce uncoupled bone turnover with decreased cortical bone formation; 2) IL-1 alpha appears to inhibit strongly the renal effects of PTHrP and weakly (if at all) its actions on bone and, thus, to decrease its hypercalcemic, phosphaturic, and hypophosphatemic actions; and 3) cosecretion of IL-1 alpha, and possibly other peptide cytokines, with PTHrP may modify the clinical expression of HHM.
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PMID:Inhibition by human interleukin-1 alpha of parathyroid hormone-related peptide effects on renal calcium and phosphorus metabolism in the rat. 131 27

This study evaluates the effect of intravenous calcitriol on parathyroid function and ionized calcium-PTH sigmoidal curve obtained during low- and high-calcium haemodialysis in 10 patients with osteitis fibrosa whose secondary hyperparathyroidism was refractory to conventional therapy. After 4 months of intravenous calcitriol, serum ionized calcium increased from 1.28 +/- 0.08 to 1.37 +/- 0.11 mmol/l (P less than 0.001), serum phosphate from 1.54 +/- 0.18 to 1.79 +/- 0.4 mmol/l (P NS), serum calcitriol from 16.7 +/- 9.9 to 34.3 +/- 6.4 pg/ml (P less than 0.001), while alkaline phosphatase decreased from 366 +/- 340 to 226 +/- 180 IU/l (P less than 0.05), osteocalcin from 46.4 +/- 20 to 34.5 +/- 15.3 ng/ml (P less than 0.05), and basal intact PTH from 1069 +/- 700 to 305 +/- 270 (P less than 0.01). Basal PTH started to decrease after 1 month of treatment prior to the increase in the ionized calcium. Because of hypercalcaemia the dialysate calcium was decreased from 1.75 to 1.5 mmol/l in three of five patients on haemodialysis, and calcium-containing solutions were replaced by calcium-free fluids in four of five patients on haemodiafiltration. Calcitriol dose, at the first month of therapy was 5.6 +/- 0.8 micrograms/week, but it was successively decreased because of hypercalcaemia to a final dose of 3.6 +/- 1.3 micrograms/week. After intravenous calcitriol the ionized calcium-PTH sigmoidal curve shifted to the left and downward. Maximally stimulated PTH and maximally inhibited PTH obtained during low- and high-calcium dialysis significantly decreased, as well as the ratio of basal PTH/PTHmax and the set point of calcium.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of chronic intravenous calcitriol on parathyroid function and set point of calcium in dialysis patients with refractory secondary hyperparathyroidism. 132 15

We report the case of a 33-year-old woman who was operated on with the diagnosis of primary hyperparathyroidism (PHP) in 1986. She had bone disease and slight hypercalcemia. Two parathyroid glands were removed with a lack of clinical improvement. Subsequently, the serum calcium levels were normal with occasional slight increases. Depressed phosphorus values and elevated alkaline phosphatases and PTH levels were also present, associated with severe bone involvement and muscular weakness. A second cervical exploration performed in 1989 disclosed only a normal parathyroid gland, which was not removed. In 1990, a thoracic CT scan showed the presence of a 1 cm mediastinal nodule close to the great vessels. A thoracotomy was performed to remove this nodule, which proved to be a parathyroid adenoma. After surgery, the patient presented with a "hungry bone" syndrome, characterized by very low levels of calcium, phosphorus and magnesium, which required enteral and parenteral calcium and magnesium supplements, plus dihydroxyvitamin D. The association of normocalcemia and intermittent hypercalcemia with severe bone disease is very rare, as is the presence of a mediastinal adenoma. This could explain the difficulty in the diagnosis in this case.
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PMID:[Primary hyperparathyroidism caused by a mediastinal adenoma with intermittent hypercalcemia and severe bone disease]. 134 71

An unusual association of a secreting renal oncocytoma and a parathyroid adenoma is described. The high level of hypercalcemia and of blood parathormone (PTH 44-68), partially reduced by nephrectomy and totally normalized by parathyroidectomy, as well as the renal tumor PTH evaluation and the ultrastructural features showing secretory granules in oncocytic cells of kidney, advocate for a double site of PTH secretion. Removal of both tumors permits a complete recovering.
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PMID:[Association of a secreting oncocytic tumor of the kidney and a parathyroid adenoma]. 135 Sep 10

High calcium leads to the secretion of calcitonin, and the administration of 1,25-dihydroxyvitamin D3 leads to a decreased transcription of the calcitonin gene. We now report the effect of chronic hypercalcemia, hypocalcemia, and vitamin D deficiency on calcitonin gene expression in vivo in the rat. Hypercalcemia was created by calcium infusions for 6 h, a high-calcium diet given to weanling rats for 3 weeks, and the transplantation of the Walker carcinosarcoma 256 cell line. Despite serum calcium as high as 22 mg/dl, there was no difference in calcitonin mRNA levels among these rats. The control genes studied, actin and somatostatin, which is specific for C cells in the thyroparathyroid tissue, also did not differ among the different groups of rats. Injected 1,25-(OH)2D3 decreased calcitonin mRNA levels at 6 h, as previously reported. Hypocalcemia, created by feeding diets deficient in calcium and vitamin D to weanling rats for 3 weeks, had no effect on calcitonin mRNA levels, in contrast to the large increases in PTH mRNA levels. These results demonstrate that calcitonin gene expression in vivo in the rat is regulated by administered 1,25-(OH)2D3 but not by changes in serum calcium.
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PMID:Regulation of calcitonin gene expression by hypocalcemia, hypercalcemia, and vitamin D in the rat. 136 Jul 44

Twelve patients (median age 44.5 years) on CAPD, who had previously used a dialysate calcium concentration of 1.75 mmol/l (for a median time of 11.5 months) were started on a low calcium dialysate (LCD) with a calcium concentration of 1.25 mmol/l and followed up for 24 weeks. During the first eight weeks, no changes in the doses of oral phosphate binders were made and serum ionized calcium decreased from 1.30 +/- 0.02 (mean +/- SE) mmol/l to 1.17 +/- 0.02 (p < 0.0001) and serum PTH (1-84) rose from 68 (median, range 16-397) ng/l to 147 (70-449, p = 0.005). After week 8, increasing doses of calcium carbonate were used to achieve target calcium levels of 1.20-1.30 mmol/l. No aluminum-containing binders were used. Calcium carbonate doses were increased from 2.3 (median, range 0.75-12) g/d to 6.8 (3.8-15.0, p = 0.0004) and serum phosphorus concentrations decreased from 2.00 mmol/l (median, range 1.25-2.67) at 8 weeks to 1.61 (1.18-2.39) at 24 weeks (p = 0.023). Serum intact PTH(1-84) values remained elevated despite the gradually increasing serum calcium concentrations. Hypercalcemia was recorded in 20/36 (56%) of blood samples during a period of four weeks before the start of LCD, and such episodes were observed in 15/89 (17%) of samples (p < 0.001) on LCD during the period when calcium carbonate doses were increased. It is concluded that on LCD 1) the number of episodes of hypercalcemia was markedly reduced, 2) higher calcium carbonate doses could be used, and thus 3) the control of serum phosphorus improved.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:CAPD with low calcium dialysate and calcium carbonate: results of a 24-week study. 136 22

Alendronate (aminohydroxybutylidene bisphosphonate) is a potent inhibitor of bone resorption but the role of the duration of intravenous infusion in its efficacy profile is unclear. In a two-centre, parallel, randomized, double-blind study, 20 patients with tumoral hypercalcemia received a single 10-mg i.v. infusion over either 2 h (group A, n = 10) or 24 h (group B, n = 10). Recurrences (n = 6) were retreated using the same regimen. Pretreatment plasma calcium (Ca) was 3.32 +/- 0.08 mM (mean +/- SEM) for all patients. Treatment A and B were associated with similar temporal profiles for onset, time to reach normocalcemia, (6 vs 5 days), nadir (day 6: 2.45 +/- 0.06 vs 2.43 +/- 0.08 mM) and time to relapse (day 21). Normocalcemia (2.15-2.55 mM) was achieved in seven (A) and nine (B) patients with other cases being partial responders (Ca: 2.65-2.76 mM). A significant decrease of urinary calcium and hydroxyproline excretion and a significant increase of PTH accompanied Ca normalization in both groups. Ca response was 50% lower on 2nd treatment with alendronate. Both treatments were well tolerated with transient mild fever being the most common adverse experience. In conclusion, whether infused over 2 or over 24 h, a single dose of 10 mg alendronate led to normalization of tumoral hypercalcemia in a large majority of cases.
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PMID:Comparison of a rapid (2-h) versus a slow (24-h) infusion of alendronate in the treatment of hypercalcemia of malignancy. 139 97

In order to prevent aluminum toxicity induced by the association of aluminum phosphate binder with 1 alpha(OH) vitamin D3 derivatives and the use of deferoxamine with its own hazards to diagnose and treat this toxicity, we have shown in 1982 that it was possible to replace the iatrogenic association of aluminum phosphate binder with 1 alpha OH vitamin D derivatives by oral calcium carbonate taken with the meals in order to bind phosphate and correct the negative calcium balance. This led to the disappearance of the crippling aluminic osteomalacia and adynamic bone diseases in our center. The effectiveness of CaCO3 without 1 alpha(OH)D3 derivatives in the control of hyperparathyroidism in dialysis patients has been proven by the appearance in four patients of our dialysis population of an histological idiopathic adynamic bone disease associated with relative hypoparathyroidism, and by the finding that more than 50% of our dialysis population treated by this sole treatment have plasma concentration of intact PTH below twice the upper limit of normal (that is, the threshold above which only significant histological osteitis fibrosa is observed). Besides the compliance problem, the limit of CaCO3 is the occurrence of hypercalcemia which occurs in about 8% of the measurements. Since calcium acetate binds twice as much phosphate for the same dose of elemental calcium as CaCO3, its use has been recommended. However, clinical experience has shown that in spite of the fact that half the dose of calcium element given as acetate does actually control predialysis plasma phosphate as well as CaCO3, the incidence of hypercalcemia is not decreased, probably because calcium availability at the alkaline pH of the intestine is much greater with Ca acetate. When hypercalcemia is frequent (and not explained by autonomized hyperparathyroidism, adynamic bone disease, overtreatment with vitamin D, granulomatosis or neoplasia) it is necessary either to decrease the dose of calcium and complete the necessary binding of phosphate by adding small doses of Mg(OH)2 or Mg carbonate, provided the dialysate Mg is decreased to 0.2 to 0.35 mmol/liter to prevent hypermagnesemia or to decrease the dialysate calcium (DCa) concentration. The decrease of DCa can be made either just when hypercalcemia occurs or on a systemic basis according to the amount of CaCO3 used and to the necessity of associating 1 alpha(OH) vitamin D3 derivatives.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Use of alkaline calcium salts as phosphate binder in uremic patients. 140 82

The aim of the study was to investigate the interrelation between induced hypercalcaemia and serum intact parathyroid hormone (S-PTH(1-84)) in normal man and in patients with primary hyperparathyroidism (PHPT) by measuring blood ionized calcium (B-Ca++) and S-PTH(1-84) before and during a controlled calcium infusion. Guided by frequent measurements of B-Ca++, we adjusted the calcium infusion rate continuously, thereby keeping B-Ca++ in a steady state at a pre-determined level approximately 0.25 mmol l-1 above baseline values. This calcium clamp technique (CCT) applied to 14 normal volunteers for 120 min established a standardized reference for parathyroid suppression and the renal physiological PTH response. The reproducibility of the method and the results obtained by the CCT were satisfactorily assessed in six of the 14 normal subjects. In normal subjects B-Ca++ was raised from 1.25 +/- 0.3 mmol l-1 (mean +/- SD) to 1.49 +/- 0.02 mmol l-1 suppressing S-PTH(1-84) to 264 +/- 9.9% of pre-infusion levels. We applied the CCT to 10 patients with PHPT for 120 min raising B-Ca++ from 1.41 +/- 0.09 mmol l-1 to 1.69 +/- 0.08 mmol l-1, thereby suppressing S-PTH(1-84) to 47.9 +/- 16.3% of pre-infusion levels. The renal handling of calcium and phosphate during CCT demonstrates the biological effects of suppressed activity of PTH on the renal tubules showing increments in the maximal tubular phosphate reabsorption in relation to the glomerular filtration rate (TmP/GFR) and decreased tubular reabsorption fraction of calcium. The described CCT is a safe and reliable dynamic test.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Calcium clamp technique: suppression of serum intact PTH by induced hypercalcaemia in normal man and primary hyperparathyroidism. 141 Dec 58

This investigation was carried out to evaluate the clinical utility and diagnostic value of serum intact PTH measurement using a recently introduced immunochemiluminometric assay (ICMA). Studies were carried out in 42 normal subjects, 24 patients with primary hyperparathyroidism, 21 patients on chronic maintenance hemodialysis, 8 patients with postsurgical hypoparathyroidism, 7 patients with cancer hypercalcemia and 6 patients with osteomalacia. A good correlation was found in normal subjects between serum ICMA PTH levels and both intact PTH measured by a two-site immunoradiometric assay (n = 42, r = 0.67, p less than 0.001) and a widely used midmolecule radioimmunoassay (n = 21, r = 0.78; p less than 0.001). Similar good correlations were found in primary hyperparathyroidism patients (IC-MA vs immunoradiometric assay r = 0.74; p less than 0.001; ICMA vs midmolecule assay r = 0.77; p less than 0.001). As far as the hypercalcemic conditions were concerned, in 5 patients with mild primary hyperparathyroidism, ICMA PTH levels were in the upper range of those found in normal subjects, even though they were inappropriately high in respect to serum calcium values. However, serum ICMA PTH levels were clearly suppressed or undetectable in the majority of patients with cancer hypercalcemia or postsurgical hypoparathyroidism. Following calcium and EDTA infusions in patients with primary hyperparathyroidism, the behaviour of ICMA PTH levels in general parallelled that of immunoradiometric PTH assay, thus indirectly suggesting the ability of the method to measure the intact molecule.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Conventional and new diagnostic applications of a two-site immunochemiluminometric assay for parathyroid hormone. 144 86


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