Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0221002 (primary hyperparathyroidism)
 4,921 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum samples from eight dogs with primary hyperparathyroidism, seven dogs with hypercalcemic lymphosarcoma (hypercalcemia of malignancy), and four dogs with primary hypoparathyroidism were submitted to the Animal Health Diagnostic Laboratory at Michigan State University for intact parathyroid hormone (PTH) assay. When compared with the adjusted total serum calcium concentration, the intact PTH concentration was consistent with the correct diagnosis in all cases. Two dogs with hypercalcemic lymphosarcoma were mildly azotemic. In both of these cases the intact PTH concentration was consistent with hypercalcemia of malignancy despite the presence of azotemia. These data support a significant role for intact serum PTH assay in the differential diagnosis of disorders of calcium metabolism.
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PMID:Intact parathyroid hormone assay and total calcium concentration in the diagnosis of disorders of calcium metabolism in dogs. 271 61

Malignant hypercalcemia can be associated with a biochemical syndrome very similar to that encountered in primary hyperparathyroidism. The putative tumoral factor responsible for this syndrome has been isolated very recently from conditioned medium of a cultured lung squamous cell carcinoma (BEN), cDNA clones characterized, and an amino-terminal fragment synthesized. We investigated and compared the effect of this synthetic amino-terminal fragment of parathyroid hormone-related peptide [PTHrP-(1-34)], to purified PTHrP-(1-141) isolated from the same lung squamous cell carcinoma, and to bovine parathyroid hormone [bPTH-(1-34)] on adenosine 3',5'-cyclic monophosphate (cAMP) production and sodium-dependent phosphate transport (NaPiT) in opossum kidney (OK) epithelial cells. PTHrP-(1-34) and bPTH-(1-34) were equipotent in eliciting a 30-fold increase of cAMP production. NaPiT, as assessed by measuring the initial rate of Pi uptake, was inhibited in a concentration-dependent manner by either synthetic peptide. Half-maximal inhibition was observed with approximately 0.03-0.1 nmol/l of either bPTH-(1-34) or PTHrP-(1-34). At 10 nmol/l, either peptide produced an inhibition of 55 +/- 4 and 53 +/- 6%, respectively. This effect was specific for Pi, since the Na-dependent transport of glucose or alanine was not altered by either peptide. In OK cells dose-dependent stimulation of cAMP production and inhibition of NaPiT were also observed with purified native PTHrP-(1-141). In LLC-PK1 cells, which are devoid of PTH receptors, none of the peptides affected NaPiT. These results demonstrate a direct and specific effect of tumoral PTHrP on cAMP production and NaPiT in cultured renal epithelial cells in a way similar to bPTH.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of synthetic tumoral PTH-related peptide on cAMP production and Na-dependent Pi transport. 284 53

Increased bone resorption (BR) and increased renal tubular reabsorption of calcium (TRCa) may both be involved in the pathogenesis of hypercalcemia of malignancy (HM). We have evaluated the relative importance of these two mechanisms in 33 patients with HM after extracellular volume expansion and after single infusion of clodronate (C12MDP: 500 mg iv over 8 h). The fasting urine Ca/creatinine ratio was taken as an index of BR (BRI). An index of TRCa was calculated (TRCaI) from a nomogram based on the relationship between urine Ca excretion per unit of glomerular filtration rate and plasma Ca (PCa). Mean (+/- SEM) PCa fell from 3.29 +/- 0.07 to 2.69 +/- 0.05 mmol/l three days after C12MDP (n = 33, p less than 0.001), a response similar to that obtained with repeated daily iv injections of 500 to 1000 mg C12MDP. The pathogenesis of hypercalcemia varied according to the type of neoplasm. BRI was the highest in multiple myeloma and breast tumors. TRCaI was markedly increased in squamous-cells lung, bladder, kidney and liver carcinomas, reaching levels observed in primary hyperparathyroidism. TRCaI was normal in most cases of multiple myeloma. Breast tumors appeared to be heterogeneous with respect to TRCaI. The fall in PCa in response to a single infusion of C12MDP was usually most marked in cancer patients with elevated BRI and normal TRCaI. It was very modest in patients with high TRCaI and slightly elevated BRI. In conclusion, this study confirms that stimulation of bone resorption is not the only mechanism of the maintenance of hypercalcemia of malignancy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bone and renal components in hypercalcemia of malignancy and responses to a single infusion of clodronate. 297 82

We compared the utility of measurements of serum intact human PTH-(1-84) and midregion human PTH-(44-68) in patients with disorders of extracellular calcium metabolism. Serum midregion PTH was determined by RIA, and serum intact PTH was measured by a sensitive and specific immunoradiometric two-site assay. The serum intact PTH concentrations in 70 patients with primary hyperparathyroidism were above the normal range in 69, and thus widely separated from the levels in 40 patients with hypercalcemia of malignancy, in whom serum intact PTH values were usually below normal. In contrast, both groups had overlapping serum midregion PTH values. In patients after renal transplantation and those with chronic renal failure, serum intact PTH levels were in the normal range twice as often as were serum midregion PTH values. The intact PTH assay was also superior in detecting venous gradients of the hormone and changes in PTH secretion caused by altered serum calcium concentrations, and serum intact PTH was remarkably low in hepatic venous effluent. We conclude that this new assay for serum intact PTH is superior to the midregion RIA in investigating parathyroid function in several different clinical conditions.
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PMID:Two-site assay of intact parathyroid hormone in the investigation of primary hyperparathyroidism and other disorders of calcium metabolism compared with a midregion assay. 329 61

Aliquots of the same serum sample from 10 proven and 10 probable cases of primary hyperparathyroidism (1 degree HPT) and 25 of hypercalcemia of malignancy (HCM) were sent to two different laboratories for C-terminal or midmolecule and N-terminal immunoreactive parathyroid hormone (iPTH) assays and total serum calcium measurements. Elevations in iPTH were observed in 70% to 95% of 1 degree HPT and 13% to 46% of HCM cases. There was a good correlation among the assays in the 1 degree HPT group. A significant correlation was found only between the C-terminal and N-terminal assays from the same laboratory in the HCM group. Only one (5%) of 20 1 degree HPT patients had normal iPTH in all assays while only one (4%) of 25 HCM patients had elevated iPTH in all assays. This study shows that currently available assays for iPTH can detect elevations in most patients with 1 degree HPT and can discriminate them from HCM. When renal function is impaired an N-terminal assay can still discriminate.
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PMID:Comparison of commercially available parathyroid hormone immunoassays in the differential diagnosis of hypercalcemia: a reanalysis. 342 89

A recently developed chemiluminescent immunoassay for 1-84 intact parathyroid hormone (PTH) demonstrated increased specificity by virtue of two-site antibody binding and increased sensitivity by use of a chemiluminescent technique. Basal PTH levels were measured in three groups of subjects: (1) normal (n = 82), (2) hyperparathyroidism (n = 31), and (3) patients with hypercalcemia of malignancy (n = 16). There was good discrimination between normal (1.2 to 9.4 pmol/L) and hyperparathyroid subjects (9.2 to 53.4 pmol/L). In persons with hypercalcemia of malignancy all PTH levels were within the normal range (0.8 to 5.2 pmol/L) or suppressed. PTH release was stimulated by the intramuscular injection of 100 IU salmon calcitonin in 6 normal controls, 10 patients with primary hyperparathyroidism due to adenoma, and 5 with four-gland hyperplasia. There was no significant rise in PTH concentration and out of the normal range in the control subjects, but the adenoma patients demonstrated a mean rise of 24.4%, 26%, and 33%, and hyperplasia patients, a mean rise of 37%, 47%, and 37% over basal levels at 120, 180, and 240 minutes. The mean absolute rise in PTH concentration was 13.4 +/- 7.7 pmol/gm of parathyroid tissue in the adenomas and 27.2 +/- 9.5 pmol/gm of parathyroid tissue in the hyperplastic glands; this difference was significant (p less than 0.05). Serial blood samples from a central vein were taken at surgery for hyperparathyroidism, and the rate of decay of the intact hormone was studied in 9 patients after removal of the parathyroid tissue. This decay was rapid with a half-life of 300 seconds. We conclude that this new specific and sensitive intact PTH assay will provide a valuable means of investigating dynamic aspects of parathyroid physiology.
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PMID:Studies in patients with hyperparathyroidism using a new two-site immunochemiluminometric assay for circulating intact (1-84) parathyroid hormone. 368 55

The relative efficacy of five drugs in the treatment of hypercalcemia of malignancy was assessed in a randomized study. The drugs were oral phosphate, mithramycin, glucocorticoids, indomethacin, and ethane-1-hydroxy-1, 1-diphosphonate (EHDP). No single agent was universally effective. Oral phosphate and mithramycin were the most efficacious, each producing a decrease in serum calcium concentrations in four of five patients, although there were serious disadvantages with the use of each. Glucocorticoids were effective in only two of five patients who received randomized treatment. A further five patients received nonrandomized treatment with glucocorticoids, and only three of these showed response. Indomethacin was effective in only one of five patients to whom it was given, and EHDP was effective also in only one of five patients. The new diphosphonate, 3-amino-1-hydroxypropane-1, 1-diphosphonate (APD) was evaluated in the treatment of hypercalcemia in 13 patients with malignant disease and two with primary hyperparathyroidism. APD caused a significant decrease in serum calcium concentration in nine of 12 patients within 72 hours. These results indicate that there is no currently available pharmacologic agent that is entirely satisfactory in the treatment of hypercalcemia. The most effective agents were mithramycin, oral phosphate, and APD. Glucocorticoids and orally administered EHDP showed limited effectiveness, and indomethacin was ineffective in the majority of patients.
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PMID:Comparative study of available medical therapy for hypercalcemia of malignancy. 621 78

Humoral hypercalcemia of malignancy (HHM) results from elaboration by tumors of a circulating bone-resorbing factor(s). THe specific mechanism responsible for this bone resorption is poorly understood, and no comprehensive study employing quantitative histomorphometric analyses of bone biopsies obtained from living patients with HHM has been reported. We describe bone histology and quantitative bone histomorphometry in bone biopsies obtained from seven patients defined biochemically (elevated nephrogenous cAMP excretion) and histologically (no tumor in biopsy sample) as having HHM. These biopsies are compared to biopsies from nine patients with primary hyperparathyroidism (HPT). Compared to patients with HPT, those with HHM displayed (mean +/- SD) greater osteoclastic activity (osteoclast surface, 8.6 +/- 6.1% vs. 2.7 +/- 1.5%; P less than 0.001) and more frequent empty lacunae (9.2 +/- 4.0% vs. 5.8 +/- 3.0%; P less than 0.01), but markedly reduced osteoblastic surface (2.5 +/- 3.1% vs. 13.8 +/- 7.0%; P less than 0.001), osteoid surface (12.9 +/- 11.9% vs. 42.0 +/- 15.0%; P less than 0.001), and osteoid volume (0.3 +/- 0.3% vs. 1.3 +/- 1.0%; P less than 0.01). These findings directly confirm the presence of humorally mediated bone resorption and indicate a striking uncoupling of osteoclast and osteoblast activities in bone from patients with HHM. These findings are in sharp contrast to those in HPT patients, where osteoclast and osteoblast activities are tightly coupled, and net skeletal calcium loss is minimal. This uncoupling provides a mechanism for the marked skeletal calcium losses observed in patients with HHM.
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PMID:Quantitative bone histomorphometry in humoral hypercalcemia of malignancy: uncoupling of bone cell activity. 708 51

Humoral hypercalcemia of malignancy (HHM) is a common paraneoplastic syndrome mediated by tumor-derived parathyroid hormone-related peptide (PTHRP), which bears structural and functional similarities to PTH. Thus the clinical features of HHM are very similar to those of primary hyperparathyroidism (1 degree HPT), a prototype of humoral hypercalcemia caused by PTH. On the other hand, HHM syndrome differs from 1 degree HPT in several aspects, including serum 1,25(OH)2D levels, acid-base balance, and bone remodeling process, the reason of which remains largely unknown. We approached these questions using a unique animal model of HHM, nude rats implanted with PTHRP-overproducing human carcinomas. In this review we will summarize the results and discuss the implications in understanding the disease mechanism.
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PMID:Humoral hypercalcemia of malignancy: some enigmas on the clinical features. 776 74

Hypercalcemia of malignancy is due either to local osteolysis at the site of bone metastases or to production by the malignancy of parathyroid hormone-related peptide, which shares some of the effects of parathyroid hormone. We used a radioimmunoassay (antiserum specific to the amino-terminus) to measure serum parathyroid hormone-related peptide levels in controls (n = 61), chronic renal failure patients (n = 10), patients with primary hyperparathyroidism (n = 19), cancer patients with (n = 35) or without (n = 57) hypercalcemia and/or bone metastases (n = 53 and n = 39, respectively), and patients with hematologic malignancies (n = 15). We set the upper limit of normal of the parathyroid hormone-related peptide assay at 2.7 pmol/L. The peptide was undetectable in two-thirds of healthy controls. Renal failure did not interfere with the assay. Eighteen of the 19 patients with primary hyperparathyroidism had normal levels. In contrast, 82% of patients with humoral hypercalcemia of malignancy (i.e., without detectable bone metastases) had increased levels; in this subgroup there was a significant inverse correlation between serum levels of the peptide and phosphorus. Elevation of parathyroid hormone-related peptide levels was less common among hypercalcemic patients with metastatic bone disease (38%). Four of the seven hypercalcemic patients with hematologic malignancies had elevated parathyroid hormone-related peptide levels. In our overall study population, serum calcium levels were weakly but significantly correlated with parathyroid hormone-related peptide levels. In conclusion, elevated parathyroid hormone-related peptide in a patient with hypercalcemia suggests a malignant disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Contribution of parathyroid hormone-related peptide to the evaluation of hypercalcemia. 778 31


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