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)

This two-site immunoradiometric assay for human parathyrin-related protein 1-86 (PTHRP1-86) in plasma uses a mouse monoclonal antibody to PTHRP1-34 coupled to cellulose particles for immunoextraction of N-terminal immunoreactivity, and a rabbit antiserum to PTHRP37-67 that is indirectly labeled with 125I-labeled PTHRP37-67 for quantifying the bound analyte. The detection limit of the assay is 0.23 pmol/L, corresponding to 0.4 pg (0.04 fmol) per tube, for a sample volume of 200 microL. Recovery of PTHRP1-86 added to serum is essentially quantitative, and within- and between-batch precision is 4.4% and 11.1%, respectively. PTH1-84, PTHRP18-34, PTHRP9-34, PTHRP1-34, and PTHRP37-67 do not cross-react in the assay at concentrations up to 2 nmol/L. Plasma concentrations of PTHRP1-86 were below or close to the detection limit of the assay in normal subjects and in patients with primary hyperparathyroidism, hypoparathyroidism, chronic renal failure, and normocalcemic malignancy. In 37 hypercalcemic patients with various malignancies, we found detectable PTHRP1-86 concentrations in 35 (95%, mean 7.4 pmol/L, range 0.46-24.7). The data support the proposed humoral role of PTHRP in cancer-associated hypercalcemia and suggest that the assay has clinical utility in the differential diagnosis of hypercalcemia.
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PMID:Development and validation of an immunoradiometric assay of parathyrin-related protein in unextracted plasma. 203 20

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 Subsequently, this treatment had to be withdrawn because of upper gastrointestinal bleeding, and hypercalcemia recurred.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

To clarify the mechanism of secondary hyperparathyroidism in chronic renal failure at the parathyroid hormone (PTH) synthesis level, we measured PTH messenger RNA (mRNA) levels in parathyroid glands in a rat model of chronic renal failure. Four weeks after 7/8 nephrectomy, hyperplasia of parathyroid glands was evident and serum PTH levels were elevated. Serum concentration of calcium, inorganic phosphate, and 1,25-dihydroxyvitamin D (1,25(OH)2D) of rats with chronic renal failure were not detectably different from those of sham-operated rats. In chronic renal failure rats, PTH mRNA levels were elevated both per RNA and per DNA of parathyroid cells, suggesting increased PTH mRNA levels per cell. The elevated levels of PTH mRNA were returned to normal levels by achieving supraphysiological concentrations of 1,25(OH)2D3 given i.p. twice at 24 and 48 hours before sacrifice, although this was attended by slight hypercalcemia. A synthetic analogue of vitamin D, 22-oxa-1,25(OH)2D3, also suppressed PTH mRNA to normal levels, but without hypercalcemia. These data suggest that secondary hyperparathyroidism in early chronic renal failure may be due in part to the resistance of parathyroid cells to the physiological concentration of 1,25(OH)2D in circulation on PTH synthesis and that 22-oxa-1,25(OH)2D3 may be useful in the management of secondary hyperparathyroidism of chronic renal failure.
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PMID:Regulation of parathyroid hormone synthesis in chronic renal failure in rats. 206 3

We have examined the effects of the diphosphonate, clodronate, in 9 haemodialysis patients with severe hyperparathyroid bone disease. Clodronate (300-600 mg infused after dialysis on 5 consecutive occasions) significantly decreased mean serum calcium, phosphate and hydroxyproline. This was associated with an increase in serum immunoassayable parathyroid hormone and activity of alkaline phosphatase. These changes reversed 2-4 weeks after stopping treatment but were sustained when treatment with oral clodronate (1.6 g daily) was supplemented for 2 weeks. Our findings suggest that intravenous clodronate is capable of inhibiting osteoclast-mediated bone resorption in chronic renal failure. The therapeutic potential of clodronate alone or with vitamin D derivatives merits further evaluation, particularly in patients with severe hyperparathyroidism, when the use of D metabolites alone is precluded by the presence of hypercalcaemia.
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PMID:Effects of clodronate in severe hyperparathyroid bone disease in chronic renal failure. 214 21

Eighty six consecutive thallium-technetium subtraction parathyroid scans performed over a three year period for hypercalcaemia have been evaluated. Twelve had chronic renal failure, 11 had hypercalcaemia due to non-hyperparathyroid causes and in 10 the imaging study was technically inadequate. The remaining 53 technically adequate studies performed for hypercalcaemia clinically thought to be possibly due to hyperparathyroidism have been analysed. Of 20 (38%) positive scans, 13 came to surgery (10 correctly localized parathyroid adenomas, 2 with multiple gland hyperplasia, and 1 papillary carcinoma of the thyroid). Of 33 (62%) negative scans, 9 had surgical exploration on the basis of strong clinical grounds and all had parathyroid adenomas. Multiple biochemical parameters have been assessed in relation to a positive outcome on scan. The adjusted calcium-phosphate product and the ratio of the adjusted calcium-phosphate product to creatinine (Ca x P/Cr) were both significantly lower in the scan positive group (P less than 0.01). The scan positive group had a significantly higher mean level of PTH (P less than 0.001) and lower mean level of phosphate (P less than 0.001). The present experience shows that parathyroid imaging is useful in localizing parathyroid adenomas in 50% of cases (10 out of 19). This figure is at the lower end of the range of previously published results. It is less effective in demonstrating multiple gland hyperplasia. The decision as to whether to undertake surgical exploration when the scan is negative has been based successfully on clinical judgement. We feel that an analysis of this nature is important, as it gives insights into the practical relevance of parathyroid imaging in the context of routine clinical work.
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PMID:A clinical audit of thallium-technetium subtraction parathyroid scans. 217 Sep 59

The phenomenon of calciphylaxis as defined by Selye is a condition of hypersensitivity that results in acute local calcification of various organs, with a whole host of morbid processes. Nephrocalcinosis and cutaneous calcifications have long been recognized in patients with chronic renal failure, but they have not often been reported in acute hyperparathyroidism or other causes of calcium-phosphate metabolism aberrations. The pathogenesis is not clear, and both the sensitizer and challenging agent in the hypersensitivity theory are often elusive, though hypercalcemia is the most consistent factor. The clinical features vary according to the organs affected and often mimic a gamut of more common conditions. Treatment is primarily supportive, with specific measures only possible when a sensitizer or challenger is identified. Correction of the hypercalcemia is, however, imperative. It is important to recognize this rare condition to avoid the more serious end results often reported.
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PMID:Calciphylaxis and systemic calcinosis. Collective review. 218 92

Parathyroid hormone-related protein (PTHrP) is invoked as the cause of humoral hypercalcaemia of malignancy (HHM); it is contained in the keratinocyte layer of normal skin; and there is evidence that is is produced by fetal parathyroids. Antibodies against synthetic PTHrP peptides have been raised in rabbits and sheep. This immunohistochemical study has found that primary parathyroid adenomata and hyperplastic glands from patients with chronic renal failure stain positively with antisera against PTHrP(1-34) and PTHrP(50-69). Primary hyperplastic glands are negative. No staining with anti-PTHrP(106-141) antiserum could be detected immunohistochemically in any of the parathyroid adenomata or hyperplasia.
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PMID:Immunohistochemical localization of parathyroid hormone-related protein in parathyroid adenoma and hyperplasia. 219 48

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

We compared measurements of parathyroid hormone (PTH) using two assays, in order to detect intact PTH and midregion/C-terminal PTH (M/C-PTH) in a variety of calcium metabolic disorders. The series consisted of a total of 101 patients, including subjects with primary hyperparathyroidism (n = 24), hypoparathyroidism (n = 18), hypercalcaemia of malignancy (n = 10), moderate chronic renal failure (n = 14), chronic renal failure undergoing haemodialysis (n = 19), and small bowel disorders (n = 16). The intact PTH assay was superior to the M/C-PTH assay in reflecting parathyroid function in primary hyperparathyroidism, hypoparathyroidism and hypercalcaemia of malignancy. In patients with chronic renal failure, both assays were indicators of a comparable number of patients with elevated PTH levels. Intact PTH proved most reliable in detecting changes in parathyroid hormone secretion in response to variations in ionized calcium induced by haemodialysis. In patients with extensive intestinal resection, both assays showed increased levels of PTH. It is concluded that measurement of intact PTH is a more reliable index of parathyroid function than measurement of midregion/C-terminal PTH. Thus such an approach should be the one of choice for clinical evaluation of calcium homeostasis.
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PMID:Diagnostic applicability of intact and midregion/C-terminal parathyroid hormone assays in calcium metabolic disorders. 225 16

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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