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

Prolonged immobilization may result in hypercalcemia, hypercalciuria, and osteoporosis. Although bone resorption is central to this syndrome, the mechanism of resorption is uncertain. In particular, the role of systemic calcium-regulating hormones remains unclear. In 14 immobilized subjects we measured fasting calcium excretion, 24-hour urinary calcium excretion during restricted calcium intake, the renal phosphorus threshold, plasma 1,25-dihydroxyvitamin D, nephrogenous cyclic AMP, and immunoreactive parathyroid hormone. Mean serum calcium levels were normal, but fasting and 24-hour calcium excretion were markedly elevated (0.28 mg per deciliter of glomerular filtrate and 314 mg per 24 hours, respectively). The mean levels of serum phosphorus (4.8 mg per deciliter) and the renal phosphorus threshold (4.3 mg per deciliter) were elevated. Mean plasma 1,25-dihydroxyvitamin D was strikingly reduced (9.9 pg per milliliter), as were nephrogenous cyclic (0.64 nmol per deciliter of glomerular filtrate) and immunoreactive parathyroid hormone in both assays. These findings indicate that the parathyroid--1,25-dihydroxyvitamin D axis is suppressed in patients with immobilization-induced hypercalciuria, as would be predicted by a model of resorptive hypercalciuria.
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PMID:Calcium homeostasis in immobilization: an example of resorptive hypercalciuria. 628 47

The etiology of tumor-induced hypercalcemia was investigated in a transplantable Leydig cell tumor of the Fischer rat. In this model, serum calcium rose from a baseline of 10.4 +/0 0.3 mg/dl to 12.5 + 0.4 mg/dl at day 10 and 16.4 +/- 1.3 mg/dl (p less than 0.001) at day 13 post transplant. Urinary calcium also increased from 1.52 +/- 0.17 mg/d to 3.52 + 0.72 mg/d (Day 12, p less than 0.01). Serum phosphate decreased from a baseline of 7.5 +/- 0.3 mg/dl to 5.5 +/- 0.6 mg/dl at day 13 (p less than 0.05). At day 13 serum immunoreactive parathyroid hormone levels fell 76% from baseline (p less than 0.01). Calcitonin increased from 59 +/- 2 pg/ml to 88 +/- 9 pg/ml (p less than 0.02). The plasma prostaglandin E metabolite, 13,14-dihydro-15-keto-PGE2 increased from 407 +/- 103 pg/ml to 647 +/-62 pg/ml (p less than 0.05) and the active Vit D compound 1,25(OH)2D increased from 94.8 +/- 5.2 pg/ml to 162.3 +/- 11.8 pg/ml (p less than 0.01). Urinary cyclic AMP did not decrease in parallel with the parathyroid hormone level and, in fact, increased from 146 +/- 3 nmol/d to 172 +/- 27 nmol/d (NS). Administration of the cyclooxygenase inhibitor indomethacin (20 mg/Kg/d) or hydrocortisone (50 mg/Kg/d) did not prevent the development of hypercalcemia. This model is similar to many patients with humoral hypercalcemia of malignancy who demonstrate suppression of parathyroid hormone with elevated urinary cyclic AMP excretion and may prove useful in the understanding of the responsible mechanisms.
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PMID:Hypercalcemia in association with a Leydig cell tumor in the rat: a model for tumor-induced hypercalcemia in man. 628 3

The effect of furosemide 8 X 10(-4) mol/l an 8 X 10(-5) mol/l on parathyroid hormone stimulated adenylate cyclase was studied in renal tissue slices from guinea pigs. Furosemide caused a dose-dependent inhibition of the effect of parathyroid hormone on production of cyclic AMP, without having any significant effect on the basal cyclic AMP production. Furosemide in similar concentrations did not inhibit the stimulatory effect of thyrotrophin and fluoride in human thyroid homogenates suggesting that furosemide is not an universal inhibitor of adenylate cyclase and that the inhibition is not caused by a direct action of furosemide on the adenylate cyclase enzyme. Furosemide did not interfere with binding of cyclic AMP to cyclic AMP binding protein kinase from rabbit muscle. The results indicate that furosemide exerts an inhibitory influence either upon binding of parathyroid hormone to renal receptors or upon transmission of impulse from receptor to adenylate cyclase. The inhibitory influence of furosemide on parathyroid hormone action in kidney could explain the value of furosemide in the acute treatment of hypercalcaemia, but also suggest that chronic treatment with furosemide might interfere with normal calcium metabolism.
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PMID:Effect of furosemide on parathyroid hormone stimulated guinea pig renal adenylate cyclase and thyrotrophin and fluoride stimulated human thyroid adenylate cyclase. 628 46

1 The actions of parathyroid hormone (PTH) are antagonized in vitro by the peptide [Nle-8, Nle-18, Tyr-34]-bPTH-(3-34)amide, an analogue of PTH. In this paper, the actions of the inhibitory peptide were investigated in vivo. 2 Native parathyroid hormone (bPTH-(1-84)), administered i.v. (0.17-1.51 nmol in volume of 0.3 ml) to 7 day old chicks produced hypercalcaemia but administration of the analogue in doses up to 173 nmol was ineffective in this respect. 3 The analogue failed to antagonize the hypercalcaemia produced by bPTH-(1-34) when injected, in 10 fold molar excess, 2 min before or simultaneously with bPTH-(1-34). 4 Normocalcaemia was restored in parathyroidectomized rats by intravenous infusion of bPTH-(1-84) at 32 pmol kg-1 h-1. Addition of the analogue to the infusion fluid in a 200 fold molar excess did not affect the concentrations of calcium and phosphate in the plasma, cyclic adenosine 3',5'-monophosphate (cyclic AMP) in the urine or phosphate clearance but produced a significant (P less than 0.05) rise in urinary calcium clearance. 5 The results suggest that the peptide [Nle-8, Nle-18, Tyr-34]-bPTH-(3-34)amide does not antagonize the actions of PTH in vivo and demonstrate an important dichotomy between in vitro and in vivo biological properties of the PTH analogue.
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PMID:In vitro studies on an antagonist of parathyroid hormone [Nle-8, Nle-18, Tyr-34]bPTH-(3-34)amide. 628 90

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

Recently it has been observed that Ca excretion in laboratory rats does not follow a Gaussian distribution, with approximately 10% of them excreting Ca at a rate of 2 SD above the group mean. This phenomenon has been described as spontaneous hypercalciuria (SH). Our studies were designed to define its mechanism. 48 Wistar rats were subjected to metabolic studies to identify SH, prospectively defined as Ca excretion 2 SD above the group mean during 7 d of dietary Ca deprivation (</=0.03% by analysis), in the absence of hypercalcemia, PO(4) depletion, or exaggerated natriuresis. Progenies from SH rats were found to have significantly higher urine Ca/creatinine (micrograms per milligram) (male = 38 vs. 23, P < 0.05; female = 79 vs. 60, P < 0.005) with 7/20 males and 9/26 females having values 2 SD above the means of normal. After a 12-h fast and during 10% volume expansion with saline, clearance and micropuncture studies were performed on three groups of acutely parathyroidectomized female rats; (a) normocalciuric (N) progenies from the normal, (b) normocalciuric (NC) progenies from SH, and (c) hypercalciuric (HC) progenies from SH rats. Among these groups, there was no significant difference in body weights, glomerular filtration rate, plasma ultrafiltrable Ca (4.5, 4.6 vs. 4.7 mg/100 g), PO(4), and the fractional excretion (FE) of Na or FE(PO4). FE Ca was significantly higher in HC rats (13.9%) than N (10.1%) and NC (10.7%). Segmental reabsorption of fluid and Na was comparable among the three groups. Fractional delivery (FD) of Ca was, however, significantly increased in the late proximal tubule of HC rats (62 vs. 49 and 46%, P < 0.05). The increased FDCa was no longer apparent in early or late distal tubule (6.9 vs. 6.9 and 7.6%, P = NS). Although FECa exceeded late distal FDCa in all three groups, the increment was significantly greater in HC rats (7.02%) than both N (3.4, P < 0.05) and NC rats (3.05, P < 0.02). The effects of chlorothiazide (27.5 mg/kg/d, i.p. x 7 d) were evaluated in the female offsprings of the SH rats. Before chlorothiazide, average urine Ca/creatinine (253 vs. 77.2) and cyclic AMP (26.6 vs. 13.4 mumol/mg creatinine, P < 0.001) on days 7 and 8 of the Ca-deprived diet were higher than the normal. On days 6 and 7 of chlorothiazide, average cyclic AMP (cAMP) excretion fell to normal range (11.7 vs. 12.7 mumol/mg creatinine) as Ca excretion was reduced to normal (62 vs. 59.4 mug Ca/mg creatinine). WE CONCLUDE: (a) SH, as defined in this study, is an inheritable biochemical marker and renal in origin. (b) The hypercalciuria is independent of parathyroid hormone, changes in plasma Ca and tubular handling of Na. (c) As studied in the PTX and volume expanded conditions of our experiments, decreased Ca reabsorption in superficial proximal convoluted tubule is demonstrable, but the hypercalciuria is probably mediated by diminished Ca transport by the deep nephron. The unlikely possibility of increased secretion by the terminal nephron, however, remains to be excluded. (d) In normal rats, there is internephron heterogeneity in regard to Ca transport during saline loading.
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PMID:Tubular mechanism for the spontaneous hypercalciuria in laboratory rat. 628 72

Hypercalcemia, hypercalciuria, and hyperphosphaturia were present in female dogs with adenocarcinomas derived from apocrine glands of the anal sac (CA). Remission of hypercalcemia accompanied tumor excision in all six dogs undergoing surgery, whereas tumor recurrence or growth of metastases was associated with a return of hypercalcemia. Preoperatively, the plasma concentrations of immunoreactive parathyroid hormone in all dogs were undetectable or in the low normal range. Plasma concentrations of 13,14-dihydro-15-keto-prostaglandin E2 (PGE2M) and serum 1,25-dihydroxyvitamin D were not significantly different from control dogs. Urinary cyclic AMP and hydroxyproline were increased in dogs with CA. No immunoreactive parathyroid hormone was detected in extracts from tumor tissue, and parathyroid glands from dogs with CA had ultrastructural characteristics of secretory inactivity. Lumbar vertebrae from hypercalcemic dogs had decreased trabecular bone volume and increased osteoclastic bone resorption compared with age-matched control dogs. After tumor excision, serum total calcium returned to the normal range, whereas immunoreactive parathyroid hormone increased 2- to 20-fold and 1,25-dihydroxyvitamin D decreased 2- to 8-fold. Postoperative hypocalcemia was not observed. These results indicate that CA produces a hypercalcemic factor other than immunoreactive parathyroid hormone or prostaglandin E2 that increases osteoclastic osteolysis distant from the tumor and results in hypercalcemia, hypercalciuria, and hyperphosphaturia.
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PMID:Hypercalcemia in dogs with adenocarcinoma derived from apocrine glands of the anal sac. Biochemical and histomorphometric investigations. 630 May 51

A fourteen-year-old boy developed severe symptomatic hypercalcaemia following prolonged supine bed rest for major trauma. Treatment consisted initially of intravenous saline and frusemide together with oral phosphate, followed by intramuscular salmon calcitonin. Only after mobilisation and weight bearing was a sustained fall of plasma calcium to normal achieved. Plasma immunoreactive parathormone levels using both N-terminal and mixed terminal specific antisera were always undetectable and urinary cyclic AMP levels were within the normal range throughout. However, before mobilisation, the tubular reabsorption of phosphate was reduced and that of calcium was increased thus indirectly suggesting increased parathormone activity. The hypercalcaemia was due to a combination of increased calcium release from bone and increased tubular reabsorption. We suggest that a factor other than parathormone is responsible for altered tubular handling of calcium and phosphate which develop following prolonged immobilisation in these patients.
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PMID:Analysis of the components of the hypercalcaemia in a 14-year-old boy following prolonged immobilisation. 630 Dec 6

The analysis of nephrogenous cyclic AMP (NcAMP) has been reported to be a means of estimating parathyroid function with the advantage of being rapidly and easily performed. More specific than the analysis of urinary cyclic AMP (UcAMP), it measures biological activity of the parathyroid hormone. This study tests its use in the diagnosis of primary hyperparathyroidism (HPP) and compares the results of UcAMP with those of NcAMP. Analyses of NcAMP and parathyroid hormone were performed in a group of 21 healthy controls and two groups of hypercalcemic patients, one consisting of 12 patients with HPP and the other of 14 patients with hypercalcemia of non-parathyroid origin (HCa). It was confirmed that NcAMP is a parameter of parathyroid function, analysis of which allows the diagnosis of HPP with the same precision as analysis of the carboxyterminal plasma PTH. It has the added advantage over PTH measurements of detecting low values, thus permitting documentation of parathyroid inhibition in HCa patients.
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PMID:[Usefulness of the determination of nephrogenous cyclic AMP in the diagnosis of primary hyperparathyroidism]. 630 35

A case of humoral non-parathyroid hypercalcemia in a breast cancer patient is discussed. Bone metastases developed 23 months after the first clinical evidence of increased serum calcium levels and did not appear to be etiologically involved in this case of hypercalcemia. Serum levels of I-PTH and PGE2 were normal, as were urinary c-AMP levels. Furthermore, no significant response to corticosteroid therapy was observed. However, the correlation between the activity of metastatic disease and calcemia suggests that this cancer produced humoral factor(s) with calcium-mobilizing activity.
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PMID:Humoral nonparathyroid hypercalcemia without evidence of bone involvement. 630 87


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