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

The development of nephrocalcinosis in the rat following intraperitoneal injections of various concentrations of neutral sodium phosphate (pH 7-4) was studied using histology, histochemistry, electron microscopy and quantitative techniques. Daily injections of 0-5 M phosphate consistently produced nephrocalcinosis after 6 days or more. Calcium deposits were at first confined to the basement membranes of proximal tubules; but a longer course of injections, up to 10 days, resulted in additional basement membrane calcification in the outer cortes, and outer medulla, together with intra-luminal casts, often calcified, in the outer medulla and papilla. Calcification was not found in other organs such as liver, lung, heart or aorta. Results from quantitative estimations of total kidney calcium and phosphorus suggested that it was the calcium content which was important to the initiation of nephrocalcinosis. Ultrastructural changes, suggestive of degeneration or alteration in function, were found in mitochondria of proximal tubules in experimental animals before the onset of histologically evident nephrocalcinosis. Later changes, especially to the basal part of proximal tubular cells and their basal laminae, were thought to be consequent upon the mitochondrial changes. It is suggested that the initial renal damage was caused both directly, by a toxic effect of the phosphate load on the kidney and, indirectly, by stimulation of the parathyroid glands as a result of the hypocalcaemia and hyperphosphataemia which followed an injection of phosphate. Daily doses of 1 M phosphate for 3 days produced a type of nephrocalcinosis which was more typical of that reported by previous investigators, who used high doses of phosphate. Twice daily injections of 0-25 M phosphate for 6 days did not induce nephrocalcinosis, whereas 0-375 M phosphate given twice daily for 6 days produced only minimal calcium deposits compared with animals given 0-5 M phosphate once daily for the same period. This may have important clinical implications, since phosphate has been used to control hypercalcaemia of various etiologies.
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PMID:The development of nephrocalcinosis in the rat following injections of neutral sodium phosphate. 113 87

Serum immunoreactive parathyroid hormone (iPTH) levels were increased in a 15 year old girl with pseudohypoparathyroidism, hypocalcemia, hyperphosphatemia, and minimal phosphaturic and absent hypercalcemic responses to exogenous parathyroid extract (PTE). Following normalization of the serum calcium concentration with vitamin D, serum iPTH and phosphate concentrations returned to the normal range, and phosphaturia could be clearly stimulated and hypercalcemia induced by PTE. On the other hand, the urinary cyclic adenosine 3',5'-monophosphate (cyclic AMP) excretion could not be stimulated, suggesting that in this case, there appears to be no relationship between the urinary excretion of cyclic AMP and the phosphaturic effect of PTE. The minimal phosphaturic effect and the lack of hypercalcemic effects of PTE in untreated pseudohypoparathyroidism can be explained by the secondary hyperparathyroidism causing elevated iPTH levels rather than by a defect at the level of the receptor sites. A requirement of pharmacologic amounts of vitamin D per se, however, for the responsiveness of patients with pseudohypoparathyroidism to PTE cannot be ruled out.
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PMID:Pseudohypoparathyroidism. Disappearance of the resistance to parathyroid extract during treatment with vitamin D. 113 47

A case of 53-year-old woman with a parathyroid adenoma and a parathyroid carcinoma with functioning metastases to the lungs, mediastinum and pleura is reported. The administration of inorganic phosphate solution failed to control hypercalcemia. The therapeutic methods available to deal with metastases are discussed.
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PMID:Functioning metastatic parathyroid carcinoma. 114 93

1. The bivalent cation-binding agent, cellulose phosphate, together with a low calcium diet was given for 6 days to nine patients with primary hyperparathyroidism subsequently verified at surgery. 2. Urinary calcium fell promptly by 8-4 mmol/24 h, and by 70% and reached amounts below 4-0 mmol/24 h in five of the nine patients. The magnitude of fall may have been related to increased synthesis of vitamin D by the skin in a sub-tropical environment. Plasma magnesium fell steadily and urinary magnesium fell by 80%. 3. The plasma calcium showed two types of response. In five patients there was no significant change because a reduction in calcium load was offset by a further increase in the already high tubular reabsorption of calcium. In the remaining four patients, the tubular reabsorption of calcium was at a higher level initially and failed to increase further on the experimental regime, with a corresponding fall in plasma calcium. 4. The hypercalcaemia of primary hyperparathyroidism can be explained by increased renal tubular reabsorption of calcium; net bone resorption makes only a small contribution but an additional factor dependent on the blood-bone equilibrium is not ruled out. 5. Comparison with other published data suggests that the fall in urinary calcium in response to a calcium-depleting regimen is prevented by concurrent depletion of inorganic phosphate and may be enhanced by concurrent depletion of magnesium. 6. Persistence of hypercalcaemia combined with an increase in tubular reabsorption of calcium in response to cellulose phosphate may be of diagnostic value in suspected primary hyperparathyroidism. 7. Cellulose phosphate may be of value in stone prevention in patients with primary hyperparathyroidism who are unsuitable for surgical treatment.
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PMID:Effect of cellulose phosphate and dietary calcium restriction in primary hyperparathyroidism. 114 6

The serum chloride and phosphate levels were measured and the chloride/phosphate ratios calculated in a group of eighty-four hypercalcemic patients. Although patients with hyperparathyroidism frequently had phosphate levels in the low normal range (less than 3 mg/100 ml) and chloride levels in the nigh normal range (greater than 102 mEq/L), they were nevertheless significantly different from the groups of patients with nonparathyroid hypercalcemia in whom phosphate levels were usually higher (greater than 3 mg/100 ml) and chloride levels usually lower (less than 102 mEq/L). The chloride/phosphate ratio was higher than 33 in 94 per cent of hyperparathyroid patients and lower than 33 in 96 per cent of other hypercalcemic patients. Thus, the measurements of serum phosphate and chloride levels and the calculation of the chloride/phosphate ratios were useful diagnostic screening tests that discriminated between patients with hypercalcemia of parathyroid and nonparathyroid origin with an accuracy of 95 per cent.
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PMID:Differential diagnosis of hypercalcemia by the chloride/phosphate ratio. 115 29

Thirteen muscle biopsy specimens (mainly the gluteus maximus) from 12 patients with laboratory confirmation of osteomalacia and proximal muscle weakness in 10 were examined by light and electron microscopy. Light microscopy revealed mild diffuse non-specific atrophy of the muscle fibres in 10 cases, severe generalised atrophy in one and patchy group atrophy in one. There was no myopathic change in specimens from cases with either a nutritional aetiology, or a mixed aetiology. The former, mostly women gave a history of severe chronic malnutrition often accompanied by repeated pregnancies and prolonged lactation; those with a mixed aetiology gave, in addition, evidence of a metabolic or endocrine disorder such as hyperparathyroidism, hyperthyroidism, uraemia, or treatment with anti-epileptic drugs or were of uncertain origin. Electron-microscope examination of muscle from the nutritional group showed atrophic changes in the fibres, such as loss of myofibrils, prominence of mitochondria and glycogen, loosening and folding of the basement-membrane but good preservation of the remaining myofibrils. In contrast muscle from cases of mixed aetiology showed, in addition to the atrophic features, clear degenerative changes in the myofibrils and the mitochondria, accumulation of amorphous material at the site of myofibrillar loss and of lipofuscin in muscle fibres, vascular endothelium and satellite cells. The earliest degenerative change was in the "I" band, involving actin filaments and "Z" line. The triads were generally preserved but the sarcoplasmic reticulum appeared affected in a patient with tetany and severe mitochondrial degeneration. In a patient with thyrotoxicosis, proliferation of central nuclei, "Z" line streaming and formation of "T" tubular aggregates were seen. In one patient with hyperparathyroidism and hypercalcaemia, severe myofibrillar degeneration and mitochondria showing osmiophilic deposits, possibly of calcium phosphate, were encountered. It is concluded: (1) that all osteomalacic muscle weakness is not myopathic but a non-specific atrophy occurring probably on the basis of disuse and malnutrition, and (2) patients with an added metabolic or endocrinological disorder show in addition to the atrophy, degenerative changes in the muscle fibre and its sub-cellular components consistent with myopathy, and these patients should be clearly distinguished from those with a background of malnutrition only.
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PMID:Nature of muscular change in osteomalacia: light- and electron-microscope observations. 121 91

The intrarenal role of plasma ionized calcium (Ca), on fractional phosphate excretion (FE PO4) was investigated in dogs with control of parathyroid hormone (PTH). In series 1, acute thyroparathyroidectomy was immediately followed by a constant infusion of bovine PTH (0.01 U/kg per min). Subsequent calcium chloride infusions increased Cai in plasma phosphate and decreased in the percentage of ultrafiltrable phosphate. A 20% increase in Cai significantly increased FE PO4 by +3.82 +/- 0.97% (P less than 0.01) when infused intravenously and by +2.62 +/- 1.06% (P less than 0.05) when infused in the renal artery. In contrast, a 75% increase in Cai did not significantly change FE PO4. In series 2, dogs were thyroparathyroidectomized 18 h before experiments, and no PTH infusion was initiated. A bolus of bovine PTH (30 U/kg) increased FE PO4 + 8.9 +/- 0.9% (P less than 0.001) in hypocalcemic dogs, +19.1 +/- 4.4% (P less than 0.001) in normolcalcemic dogs, and +15.5 +/- 1.5% (P less than 0.001) in hypercalcemic dogs. We conclude that increases in plasma calcium potentiate the phosphaturic effect of PTH. This potentiating effect is attenuated in marked hypercalcemia by superimposed hemodynamic and/or metabolic changes.
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PMID:Intrarenal calcium in phosphate handling. 126 84

Renal bone disease is an important cause of morbidity in patients on dialysis. The prevalence of renal bone disease, especially aluminium related bone disease, has not been studied in the Singapore dialysis population. As such, we studied 45 haemodialysis patients for renal bone disease using biochemical and radiological parameters. Selected patients underwent a renal biopsy. There were 29 males and 16 females, mean (+/- SEM) age, 44.6 +/- 13.4 years. The duration of haemodialysis ranged from two months to ten years, mean 18.5 months. 75.4% of patients had hyperphosphatasemia, 24.4% had hypocalcemia and two patients had hypercalcemia. There was a wide range in the serum parathyroid hormone levels and 55.4% of patients had serum parathyroid hormone levels > 1000 pmol/L. Patients with symptoms and radiological abnormalities had significantly higher serum parathyroid hormone and alkaline phosphatase levels than those without (P < 0.005). The desferrioxamine infusion test was positive, with an increment in serum aluminium (DL) > 100 mg/L in five patients. Skeletal survey was positive for renal bone disease in 24.4% of patients. There was a significant correlation between the serum parathyroid hormone level, DA1 and the duration of dialysis (r = 0.752, p < 0.001 and r = 0.837, p < 0.001 respectively). There was no correlation between serum parathyroid hormone, calcium, phosphate levels and DA1. The serum haemoglobin concentration and ferritin levels did not show a correlation with DA1. Bone biopsy revealed hyperparathyroid bone disease in two patients, aluminium-related bone disease in one patient and mixed uraemic osteodystrophy in one patient.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal bone disease in patients on haemodialysis: biochemical and radiological assessment. 129 14

Hypercalcemia, rather than hypocalcemia, has been observed in conjunction with severe magnesium (Mg) depletion in rat, in contrast to the development of hypocalcemia in Mg deficiency in various animal models. In the present study, a possible involvement of parathyroid hormone (PTH) in the development of hypercalcemia in rat was studied by using a newly-developed sensitive and specific radioimmunoassay system for the determination of rat PTH. In normal rat model, hypercalcemia occurred in association with a decrease of serum phosphate levels in Mg deficiency. However, serum PTH levels were not suppressed despite the occurrence of hypercalcemia, suggesting PTH as an important factor for the development of hypercalcemia. Of interest, in 5/6-nephrectomized uremic model, hypocalcemia, rather than hypercalcemia, was observed in Mg-deficient rats. Serum PTH levels seemed to be higher, but not statistically significant probably due to a small number of rats. However, infusion study clearly demonstrated that PTH secretion was significantly increased in Mg-deficient uremic rats compared with Mg-replete counterparts. The reason for an increase of serum PTH responses might be explained by Mg depletion itself in addition to a fall in serum Ca levels, because infusion study revealed that the magnitude of the stimulation of PTH secretion was increased in Mg deficiency despite the similar degrees of changes in serum Ca levels and that the set point for the suppression of PTH secretion by Ca might be altered in Mg deficiency. Taken these data together, it was strongly suggested that Mg depletion might enhance PTH secretion in rat.
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PMID:Magnesium deficiency enhances secretion of parathyroid hormone in normal and 5/6-nephrectomized uremic rats. 130 Mar 31

The use of oral calcium carbonate as a phosphate binder is often complicated by hypercalcaemia, particularly with concomitant use of vitamin D analogues. We previously found that stepwise reduction of dialysate calcium effectively countered this complication in haemodialysis patients, and have now assessed the strategy in CAPD patients. Seventeen patients underwent conversion from aluminium hydroxide to calcium carbonate and were followed for 5 months, with subsequent addition of alfacalcidol for a further 5 months. Standard CAPD dialysate (1.75 mM calcium) was used, reducing to 1.45 mM and, if necessary, to 1.00 mM in patients who became hypercalcaemic. While receiving calcium carbonate alone, 12 of the 17 patients became hypercalcaemic, this responding in four to dialysate calcium reduction to 1.45 mM. In the remaining eight patients, further reduction to 1.00 mM was required and in two patients even this failed to control hypercalcaemia adequately, necessitating reversion to aluminium hydroxide. Phosphate control remained unchanged, as did calcium x phosphorus product. There were transient increases of blood ionised calcium, and decreases of parathyroid hormone, with progressive reduction of serum aluminium and alkaline phosphatase. The addition of alfacalcidol (0.25 microgram/day) led to hypercalcaemia in six subjects, successfully countered by dialysate calcium reduction in four. The results show that standard CAPD dialysate calcium at 1.75 mM is too high for the majority of calcium carbonate treated patients and that substantial reductions of the dialysate calcium concentration are required if calcium carbonate is to be used effectively.
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PMID:Dialysate calcium reduction in CAPD patients treated with calcium carbonate and alfacalcidol. 131 83


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