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

In an attempt to elucidate the influence of 1 alpha-hydroxycholecalciferol (1 alpha OHD3) on parathyroid hormone (PTH) secretion, sequential measurements were made of 1) serum calcium and urinary excretion of cAMP in conscious perfused rats, and 2) serum calcium in nephrectomized rats; also, the effects of a single iv injection of 1 alpha OHD3 on these parameters were examined. In conscious perfused rats, 6.25 micrograms/kg (15 nmol/kg) 1 alpha OHD3 reduced the urinary excretion of cAMP (approximately 40% of the initial value; P less than 0.05), which reached a level compatible with that of parathyroidectomized rats at 4 h; this fall was sustained for 24 h. Serum concentrations of calcium (total and ionized) did not change at 6 h, and increased at 24 h. In parathyroidectomized rats which were continuously infused with bovine PTH (0.75 U/h), the vitamin D preparation had no significant effect on the urinary excretion of cAMP. Nephrectomy, followed by an injection of the vehicle (0.05 ml 99.5% ethanol), induced a transient hypercalcemia (13.12 +/- 0.39 mg/dl at 6 h). This hypercalcemic response was prevented by prior parathyroidectomy. Injections of 1.25 and 6.25 micrograms/kg 1 alpha OHD3 caused a significant suppression of the hypercalcemia (P less than 0.05 and P less than 0.1, respectively) in the presence of parathyroid glands, whereas a dose-related hypercalcemic effect was observed in their absence. These results suggest that in rats, 1 alpha OHD3, either directly or most probably after conversion into 1 alpha, 25-dihydroxycholecalciferol, 1) acutely inhibits PTH secretion without causing a significant rise in serum calcium, and 2) suppresses PTH secretion in secondary hyperparathyroidism induced by nephrectomy.
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PMID:Evidence for acute inhibitory effects in vivo of 1 alpha-hydroxycholecalciferol on parathyroid hormone secretion in rats. 626 31

Employing a cytochemical assay initially developed for measuring parathyroid hormone (PTH), bioactivity was assessed in 33 patients with malignancies. Initial studies in vitro were consistent with a role for cAMP as a second messenger in the bioassay. Cytochemical bioactivity was increased in the peripheral plasma of 10 of 16 hypercalcemic patients with elevated nephrogenous cAMP excretion, and mean levels were 10-fold higher in these patients than in 17 normocalcemic or hypercalcemic patients with normal or suppressed nephrogenous cAmP excretion, respectively. Plasma bioactivity, serum calcium, and nephrogenous cAMP excretion all fell to normal in 1 patient after tumor resection, and cytochemical bioactivity was demonstrable in the tissue culture medium in which the neoplasm was maintained. Gel chromatographic analysis revealed that a major component of plasma bioactivity eluted before rather than with PTH-(1-84) in patients with malignancy in contrast with that in patients with primary hyperparathyroidism. The studies, therefore, demonstrate the capacity of the cytochemical bioassay to measure increased activity in patients with malignancy, hypercalcemia, and elevated nephrogenous cAMP excretion; suggest that the material responsible for the activity differs from PTH-(1-84); and provide a sensitive detector system for further analysis of this material and its role in the pathogenesis of this disease.
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PMID:Malignancy-associated hypercalcemia: evaluation with a cytochemical bioassay for parathyroid hormone. 627 Jan 84

One of the hypotheses attempting to explain the etiology of the human disease X-linked hypophosphatemia (XLH) posits renal hypersensitivity to parathyroid hormone (PTH). These studies were designed to test this hypothesis in vivo, using the hemizygous hypophosphatemic (Hyp/Y) mouse as an animal model for XLH. Vehicle or 1.0 U bovine PTH (bPTH)/g BW sc was given to intact normal or Hyp mice. Two hours later a small but significant hypercalcemia was observed in both genotypes. Only normal mice remained hypercalcemic 5 h after injection. Intact normal mice, but not Hyp mice, displayed a significant bPTH-induced hypophosphatemia. Administration of bPTH caused a significant increase in both fractional excretion of phosphate (FE-P) and urinary cAMP (UcAMP) 2 h after injection. However, there was no significant differences in the magnitude of response between genotypes. In a different experiment hPTH dose-response curves (0, 0.04, 0.2, and 1.0 U bPTH/g BW sc) were constructed in normal and Hyp mice 18 h after thyroparathyroidectomy (TPTX). bPTH caused a significant hypercalcemia and hypophosphatemia in TPTX normal mice at all doses 2 h after injection. But only the highest dose of hormone caused a significant hypercalcemia in TPTX Hyp mice, and no dose caused a significant decrease in plasma P. In both genotypes a dose-dependent increase in FE-P and UcAMP was observed 2 h after bPTH administration. As with intact mice, there was no indication of a hypersensitive or exaggerated renal response in TPTX Hyp mice. In summary, results from these in vivo experiments indicate that the kidneys of Hyp mice are not hypersensitive to exogenous bPTH. Furthermore, TPTX Hyp mice appeared to exhibit "skeletal resistance" to exogenous PTH, as do osteomalacic dogs and humans. We conclude that renal hypersensitivity to PTH does not play a role in the etiology of XLH in Hyp mice.
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PMID:X-linked hypophosphatemic mice are not hypersensitive to parathyroid hormone. 627 50

A possible involvement of cyclic nucleotides (cAMP and cGMP) in the regulation of cardiac contractility and glycolysis during hypoxia was examined in spontaneously beating rat atria. A reduction of the high oxygen saturation (HiOxSa) of the incubation medium from 95-100% to half produced a rapid decline of the amplitude. The deterioration of 50% was seen after 30 sec. of hypoxia. The decline was partly antagonized by noradrenaline (NA, 1 X 10(-6) M) or hypercalcaemia (5.7 X 10(-3) M instead of 1.9 X 10(-3) M). The cAMP level remained unchanged during the first 12 min. of hypoxia, but the cGMP content increased gradually and reached a significantly increased level in 4-8 min. Paradoxically, the production of lactate decreased, after 30 sec. of hypoxia, but accelerated then 2-4 min. after the onset of hypoxia. The depletion of creatine phosphate and ATP stores was initiated after 2 min. of hypoxia. The arterial content of the active forms of phosphofructokinase and lactate dehydrogenase gradually rose during hypoxia. Sodium nitroprusside (SNP, 1 X 10(-4) M) and NA produced increases in cGMP and cAMP levels, respectively, both in HiOxSa and hypoxia. SNP induced a slight and NA a marked increase in the amplitude in HiOxSa. Verapamil (1 X 10(-6) M) decreased the contractility, but did not affect the levels of cAMP and cGMP. Both SNP and verapamil decreased the lactate production, but they could not resist the NA-induced increase in the atrial lactate level. Hypercalcaemia increased the amplitude but slightly reduced the lactate production in HiOxSa. 45Ca-uptake was reduced to about 35 per cent of control as measured between 5 and 10 min. of hypoxia. It is concluded that the lack of oxygen could have direct and parallel effects on the sarcolemma and on the mitochondria. The former could result in the deterioration of contractility and the latter in the termination of aerobic energy production. Cyclic nucleotides are not involved in either of these phenomena. However, at the low rate of anaerobic glycolysis, e.g. in HiOxSa or at the very early stage of hypoxia, cGMP could inhibit and cAMP accelerate the lactate production.
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PMID:On the role of cyclic nucleotides in the regulation of cardiac contractility and glycolysis during hypoxia. 627 32

Calcium homeostasis was studied in freely fed control, streptozotocin diabetic, long-term and short-term insulin-treated diabetic rats 7 wk after the induction of diabetes. In contrast to the short-term (5-12 day) diabetic rat model, intestinal absorption of calcium was markedly enhanced in chronically insulin-deficient animals. Moreover, conventional balance studies showed that these animals were in positive calcium balance despite severe hypercalciuria. Intestinal hyperabsorption of calcium in long-standing diabetic rats occurred despite low levels of circulating 1,25-dihydroxyvitamin D and hypercorticosteronism and was attended by hypercalcemia and suppression of both plasma parathyroid hormone (PTH) and urinary cyclic 3',5'-AMP (cAMP). Long-term insulin replacement completely normalized the intestinal hyperabsorption of calcium, corrected the plasma calcium, and significantly increased circulating PTH and urinary cAMP excretion. Insulin therapy also corrected the decreased plasma 1,25-dihydroxyvitamin D observed in untreated diabetic animals. Intestinal hyperabsorption of calcium appeared to be only partially corrected by short-term insulin therapy. The accumulated results reveal decided differences in calcium homeostasis and hormonal response between the rats with long-standing diabetes and those with diabetes of short duration.
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PMID:Calcium homeostasis in chronic streptozotocin-induced diabetes mellitus in the rat. 628 97

We report a new family with familial hypocalciuric hypercalcemia (FHH) composed by 55 living members. Of 38 studied, 10 have been found to be affected by FHH. Differences between FHH and primary hyperparathyroidism are emphasized; lack of clinical features, relative hypocalciuria for the concomitant hypercalcemia and low phosphate excretion index. The PTH and urinary cAMP are normal. It is noteworthy that the disease is benign. None of our patients have undergone surgery, and all of them are asymptomatic.
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PMID:Familial hypocalciuric hypercalcemia. Report of a new family. 628 31

To evaluate the usefulness of urinary cyclic AMP (U-cAMP) expressed as nmol/100 ml glomerulus filtrate (GF) when discriminating various hypercalcemic states, we studied 99 patients. Patients with primary hyperparathyroidism (PHPT) showed a positive correlation between individual S-calcium levels and U-cAMP, nmol/100 ml GF (females r=0.49, n=40, p less than 0.01 and males r=0.91, n=7 p less than 0.001). There was also a correlation between U-cAMP, nmol/100 ml GF, and the weight of the adenomas (females r=0.36, n=32, p less than 0.05) and males r=0.79, n=6, p less than 0.05). Patients with PHPT and normal renal function excreted more U-cAMP than controls, 6.0 +/- 1.6 versus 4.3 +/- 1.0 nmol/100 ml GF (mean +/- SD). Of 47 patients with PHPT and normal renal function, 29 showed values below the upper normal limit, 6.3 nmol/100 ml GF (mean +/-2 SD), of the control group; the overlap was 62%. When U-cAMP was expressed as mumol/24 hours, the overlap was 40/47 (85%) and, when expressed as mumol/g creatinine, 31/47 (66%). Three patients with sarcoidosis and two with malignancies and hypercalcemia showed excretory values of U-cAMP, nmol/100 ml GF, above the upper normal limit. Patients with acromegaly or prolactinoma showed normal values of U-cAMP, nmol/100 ml GF. The present data indicate that all three types of determinations of urinary cAMP based on 24 hour urine collections are of little value in the differential diagnosis of hypercalcemic states.
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PMID:Urinary cyclic AMP corrected for glomerular filtration rate in the differential diagnosis of hypercalcemia. 628 11

In prepuberal female rats with acute bilateral nephrectomy or chronic subtotal nephrectomy, the increase of ovarian cAMP concentration in response to submaximal doses of luteinizing hormone (LH 10 micrograms) and human chorionic gonadotropine (hCG 2.5 IU) was diminished (CO + 2.5 IU hCG 488 +/- 49 pmoles cAMP/mg protein; NX + 2.5 IU hCG 366 +/- 56. P less than 0.05). The cAMP response to follicle stimulating hormone (FSH) was unchanged. The abnormality was found both after administration of LH in vivo and incubation of ovaries with LH in vitro. Similarly, plasma estradiol concentrations in response to submaximal hCG stimulation were diminished. Basal cAMP concentrations and cAMP concentrations after maximal stimulation were unchanged. The defect was observed both in ovaries of untreated prepuberal rats, of pregnant mare serum (PMS)-treated rats (follicular phase) and PMS/hCG-treated rats (luteal phase). Diminished ovarian cAMP response to LH was observed both in parathyroid intact and in parathyroidectomized rats. Administration of 1,25(OH)2D3 in physiological doses (60 ng/kg) to acutely uremic rats restored diminished ovarian cAMP response to submaximal LH stimulation irrespective of parathyroid status. The effect of 1,25(OH)2D3 could not be reproduced by hypercalcemia resulting from intraperitoneal calcium injection. In vivo administration of indomethacin further diminished ovarian cAMP response in uremic animals and had no effect in control animals. Incubation of ovaries with PGE1 and PGE2 increased basal and stimulated cAMP concentrations and abolished the difference between control and uremic animals. The diminished response of ovarian cAMP content to submaximal doses of hCG was not corrected by bromocriptine (1 mg/kg) despite normalization of hyperprolactinemia. The present study shows diminished ovarian cAMP and plasma estradiol response to LH in experimental uremia. It documents a role of 1,25(OH)2D3 and prostaglandins in the genesis of this abnormality.
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PMID:Diminished response of ovarian cAMP to luteinizing hormone in experimental uremia. 629 98

Thirty-four patients presenting to a urology clinic over a five-year period with renal calculi and either hypercalciuria or hypercalcemia were investigated by measurements of serum parathyroid hormone and urinary calcium and cAMP. Ten patients were hypercalcemic and were found to have primary hyperparathyroidism. Of the remaining patients all but one had excessive urine calcium excretion after an oral calcium load. In addition, 9 patients were shown to have elevated fasting urinary calcium levels while on a low-calcium diet, raising the possibility of impaired renal calcium conservation as one factor causing their hypercalciuria. The measurement of urinary cAMP levels did not contribute to the accuracy of diagnosis and did not permit further subclassification into different types of hypercalciuria. There was a decrease in urinary calcium excretion and a marked reduction in stone-related events in 10 patients with severe renal stone disease during treatment with hypocalciuric agents.
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PMID:Investigation and treatment of renal calculi associated with hypercalciuria. 630 59

We studied the effect of a transplantable Leydig-cell tumor (Rice H-500) on serum calcium, parathyroid hormone (PTH), and urinary cAMP in intact Fischer-344 rats. The tumor caused rapid and severe hypercalcemia (control = 10.5 +/- 0.1 mg/dl [mean +/- S.E.] vs. 14.6 +/- 0.9 at day 12 post tumor inoculation) without evidence of metastasis. Progressive renal impairment and death generally occurred within 15 days of tumor inoculation. Serum PTH declined from control values before hypercalcemia occurred and was significantly reduced in tumor-bearing hypercalcemic rats (mean = 60 +/- 8% of control values). Urinary cAMP excretion was increased in tumor-bearing rats (mean at day 12 post inoculation = 12.2 +/- 1.4 nmol/dl creatinine clearance vs. control = 6.2 +/- 0.2) and correlated positively with serum calcium. The Rice H-500 Leydig-cell tumor appears to secrete a humoral factor capable of causing hypercalcemia. This factor may also increase urinary cAMP excretion in a manner analogous to PTH, but it is not detected by PTH radioimmunoassay.
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PMID:Humoral hypercalcemia caused by a rat Leydig-cell tumor is associated with suppressed parathyroid hormone secretion and increased urinary cAMP excretion. 630 50


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