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)

Here we report a highly sensitive and convenient ligand binding assay for the determination of 1,25(OH)2D3 in small volumes of human plasma. This method involves: (1) extraction of vitamin D3 and its metabolites using methanol-methylene chloride with separation of phases by centrifugation; (2) gel chromatography and high pressure liquid chromatography for the quantitative isolation of 1,25-(OH)2D3; and (3) a sensitive ligand binding assay for 1,25-(OH)2D3 employing cytosol receptor from the intestinal mucosa of rachitic chicks. Using modified rachitogenic chick diets allows early (less than 4 wks) harvesting of active receptor for 1,25-(OH)2D3 in high yield. The method includes a rapid and effective procedure for stable and long-term storage of the active cytosol receptor. A convenient dextran-charcoal means is used for the separation of receptor bound from free 1,25-(OH)2D3 resulting in the achievement of a lower (less than 5%) background (i.e., nonspecific binding) than reported for other 1,25-(OH)2D3 assays. Analysis of this receptor shows it to be a saturable, single class of binding sites with a dissociation constant (Kd) of approximately 3.7 x 10-11. The final recovery of 1,25-(OH)2D3 following extraction and chromatography is 80 +/- 3% and triplicate determinations can be made on a 3 ml plasma sample. The ligand binding assay routinely detects less than or equal to 5pg of 1,25-(OH)2D3 per assay tube and the inter- and intraassay variation, based on repeated determinations of 1,25-(OH)2D3 in pooled normal human plasma, is less than 5%. Preliminary studies indicate that our methodology will permit measurement of plasma 1,25-(OH)2D3 levels in all normal subjects and in pathophysiologic states where 1,25-(OH)2D3 levels may be below or above normal values. 1,25-(OH)2D3 values (pg/ml +/- SEM) in human plasma obtained from both normals and patients with various untreated calcium homeostatic disorders were: normals = 33.5 +/- 1.8; end-stage chronic renal failure = 5.1 +/- 1.2; primary hypoparathyroidism = 18.3 +/- 2.8; primary hyperparathyroidism = 61.4 +/- 7.1; and hyperthyroidism with associated hypercalcemia = 42.1 +/- 8.4.
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PMID:An improved method for the measurement of 1,25-(OH)2D3 in human plasma. 75 33

In early chronic renal failure, the state of the bones resembles that of type II primary hyperparathyroidism. Cortical bone becomes thinner and more porous, and there is increased extent of surface remodeling. These changes are followed in turn by osteomalacia and osteitis fibrosa, although sometimes these may be alternate rather than successive stages. Bone turnover is less than would be expected for the elevation of PTH level, probably because of 1,25 (OH)2D3 deficiency. The resorption velocity and lamellar bone appositional rates are depressed, but woven bone appositional rate may be increased, possibly because of hyperphosphatemia. Bone mass reflects the summation of three independent processes: loss of lamellar bone due to hyperparathyroidism (depending on the extent of insulation by osteoid); accumulation of partly mineralized osteoid because of osteomalacia; accumulation of woven bone because of osteitis fibrosa. Osteosclerosis may be growth-related metaphyseal, subchondral or diffuse axial, and periosteal neostosis may also occur. Some patients on hemodialysis lose bone because of planing rather than lacunar or dissecting resorption, combined with depression of both lamellar and woven bone formation. Hyperparathyroid bone disease tends to improve slowly after renal transplantation. Persistent hypocalcemia reflects a defect in the calcium homeostatic system and cannot be explained solely by the known stimuli to secondary hyperparathyroidism. The increment in plasma calcium in response to PTH infusion is subnormal, both in early chronic and in acute renal failure, probably because of 1,25(OH)2D3 deficiency. This is also the most likely explanation for the depressed level of blood-bone equilibrium. The activity of all three of the PTH responsive cell systems in bone is depressed in renal failure, probably because all three require 1,25(OH)2D3 in order to function normally. In pseudohypoparathyroidism, as in chronic renal failure, hypocalcemia results from a defect in the regulation of the blood-bone equilibrium. The bone-remodeling system shows all gradations of response, from slight depression of bone turnover to overt osteitis fibrosa, but bone turnover is never as low as in PTH deficiency. These differences may reflect the presence or absence of resistance to PTH of the osteoprogenitor cell as well as of the calcium homeostatic system, or may be due to varying degrees of 1,25(OH)2D3 deficiency, as in chronic renal failure. An increase in plasma calcium in response to PTH can occur either in the untreated state or after treatment with vitamin D because either the error-correcting or remodeling system remains responsive to PTH. Pseudohypoparathyroidism may be subdivided into three types, depending on whether the urinary cyclic-AMP response to PTH remains defective despite treatment with vitamin D, improves with treatment, or is normal before treatment. Only the former is associated with the genetic syndrome of Albright's hereditary osteodystrophy...
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PMID:The actions of parathyroid hormone on bone: relation to bone remodeling and turnover, calcium homeostasis, and metabolic bone disease. Part IV of IV parts: The state of the bones in uremic hyperaparathyroidism--the mechanisms of skeletal resistance to PTH in renal failure and pseudohypoparathyroidism and the role of PTH in osteoporosis, osteopetrosis, and osteofluorosis. 78 23

The parathyroid response to EDTA infusion was measured in 23 patients with hypo- or hyperparathyroidism using two different antisera, one predominantly anti COOH-terminal (GP 62) and the other predominantly anti NH2-terminal (WC), and was compared with the responses observed in 16 controls for GP 62 and 18 controls for WC. In primary hyperparathyroidism elevated basal PTH values were found more frequently with GP 62 (6 of 10 cases) than with WC (3 of 9 cases). However, WC more frequently exhibited exaggerated responses to EDTA (8 of 9 cases) than GP 62 (7 of 10 cases). In hypoparathyroidism the basal values were not distinguishable from the normals. However, the EDTA test showed absent or low responses in 10 of 11 cases studied with GP 62. Antiserum WC showed normal responses in 4 cases with postoperative hypoparathyroidism, revealing some residual PTH secretion but not response in the 2 cases with idiopathic hypoparathyroidism. Since one of them had a normal response when measured with GP 62, secretion of an immunologically abnormal PTH may be suspected. In chronic renal failure normal responses can be observed despite an abnormal basal PTH level, since it is falsely elevated by the accumulation of COOH-terminal fragments.
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PMID:[Parathyroid response to EDTA: effect of the immune heterogeneity of the parathyroid hormone]. 81 17

A radioimmunoassay for the measurement of immunoreactive parathyroid hormone (PTH) in human serum is described. The assay is based on the ability of human parathyroid hormone (h-PTH) to compete with 125I-labelled bovine parathyroid hormone (b-PTH) for binding to a guinea-pig antiserum directed against b-PTH. The linear part of the standard curve was parallel with dose response curves for anti-b-PTH serum reacting with dilutions of sera from patients with primary hyperparathyroidism and from h-PTH purified from human parathyroid adenomas, indicating that levels of immunoreactive PTH could be expressed as b-PTH equivalents. The range in 62 healthy blood donors was 1.1-2.5 ng b-PTH Eg./ml. The reproducibility was satisfactory, and the sensitivity permitted the measurement of PTH concentrations down to 0.8 ng b-PTH Eg./ml. No crossreaction with h-CT, h-STH or h-ACTH was observed. The clinical value of the assay has been considered in a number of patients with various disorders of calcium metabolism, diagnosed and treated conventionally. About 80 per cent of patients with primary hyperparathyroidism had elevated PTH levels on one or more occasions before surgery. In patients with chronic renal failure of other aetiology than primary hyperparathyroidism the levels were usually far higher. Patients with primary hyperparathyroidism and increased S-creatinine had higher PTH levels than those with normal S-creatinine. After parathyroidectomy all previously increased PTH levels became normal or low. High PTH concentrations were found in 3 patients with normocalcaemic hyperparathyroidism who at operation were shown to have parathyroid adenomas. However, in normocalcaemic patients there were also some falsely elevated PTH values which limit the diagnostic value of the assay in this group of patients. Low PTH values were observed in patients with hypercalcaemia due to malignant disorders, indicating that PTH determination may be of some value in the diagnosis of patients with hypercalcaemia of unknown origin.
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PMID:The diagnostic value of a radioimmunoassay for parathyroid hormone in human serum. 117 15

A radioimmunoassay for serum immunoreactive parathyroid hormone (iPTH), which has had widespread clinical use for five years, is described in detail. The iPTH results in large groups of patients are reported, and are discussed in relation to the specificity of the assay and in relation to other assays. The assay has excellent precision and is highly proficient in discrimination of groups of patients. Ninety-three percent of 412 patients with surgically proven primary hyperparathyroidism were confidently separated from normal subjects or patients with hypercalcemia owing to other causes, while 86 percent of 160 patients with chronic renal failure and secondary hyperparathyroidism had iPTH values more than 2 S.D. above the normal mean. Results in patients with ectopic hyperparathyroidism were lower than in primary hyperparathyroidism although these groups showed considerable overlap. The antiserum used in this assay for iPTH appears to be specific for the carboxy-terminal region of the secreted or intact form of PTH but recognizes predominantly the secreted form rather than carboxy-terminal fragments believed to be in the circulation. It does not recognize amino terminal fragments. The assay is useful in selective venous catheterization for preoperative localization of hyperfunctioning parathyroid tissue.
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PMID:Parathyroid hormone: radioimmunoassay and clinical interpretation. 118 Apr 81

A new, highly sensitive radioreceptor assay, which does not require high-performance liquid chromatography, has been developed for the determination of 1,25-dihydroxyvitamin D3 (1,25-(OH2)D3) in serum. The assay involves rapid extraction of serum, Sep Pak silica purification, and addition of 1,25-dihydroxyvitamin D3 receptor, radiolabeled 1,25-dihydroxyvitamin D3, bovine serum albumin, and monoclonal antibody to specifically precipitate the receptor. This method is sensitive to 0.3-0.6 pg/tube, with B50 occurring at 5.8 pg/tube. This sensitivity combined with overall recovery of 1,25-dihydroxyvitamin D3 (81.5 +/- 5.2%, n = 50, mean +/- SD) allows the measurement of serum 1,25-(OH)2D3 in duplicates with only 0.5 ml of serum. Intra- and interassay coefficient of variation were 9.5 and 14.6%, respectively. Dilution analysis, analytical recovery of added 1,25-dihydroxyvitamin D3, and comparison with a standard method using HPLC have been used to validate the assay. Serum 1,25-dihydroxyvitamin D3 level was for normal adults, 36.6 +/- 10.5 pg/ml (n = 14); in primary hyperparathyroidism, 98.9 +/- 19.9 pg/ml (n = 16); in chronic renal failure, 17.8 +/- 5.1 pg/ml (n = 12). This method allows large numbers of samples to be processed at once. Further, the method is rapid and provides an accurate assay using small amounts of serum.
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PMID:A new, highly sensitive assay for 1,25-dihydroxyvitamin D not requiring high-performance liquid chromatography: application of monoclonal antibody against vitamin D receptor to radioreceptor assay. 133 39

The diagnosis of humoral hypercalcaemia of malignancy often presents considerable clinical problems. We have studied parathyroid hormone-related peptide (PTHrP) in serum from patients with humoral hypercalcaemia of malignancy (N = 22), hypercalcaemia of malignancy with skeletal metastases (17), histologically confirmed primary hyperparathyroidism (21) and hypercalcaemic patients with various benign diseases (9). PTHrP measurements were also made in normocalcaemic patients with various malignancies (23), endocrine diseases (13), sarcoidosis (22) and chronic renal failure (17). PTHrP was measured by a novel radioimmunoassay using rabbit antibodies directed towards the midregion of the molecule. Immuno- or silica cartridge extraction of serum before radioimmunoassay enabled us to measure PTHrP in all samples, which may add further information about circulating forms of PTHrP. PTHrP was clearly elevated in patients with humoral hypercalcaemia of malignancy (5.0 +/- 4.7 pmol/l) (mean +/- SD, N = 12) and when the kidney function was impaired (4.0 +/- 0.9 pmol/l) (N = 15) (silica cartridge extraction), whether the subject was hypercalcaemic or not. Some patients with endocrine diseases, including two with primary hyperparathyroidism, had slightly elevated serum PTHrP concentrations, while they were normal in sarcoidosis. In healthy subjects the levels were 1.1 +/- 0.5 pmol/l (N = 15) after immunoextraction and 0.8 +/- 0.2 pmol/l (N = 33) after silica cartridge extraction.
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PMID:Parathyroid hormone-related peptide, measured by a midmolecule radioimmunoassay, in various hypercalcaemic and normocalcaemic conditions. 144 40

Calcitonin is a hypocalcaemia producing hormone and is secreted by C-cells of the thyroid. The current study was undertaken on a hypothesis that C-cell hyperplasia may develop in the secondary hyperparathyroidism of chronic renal failure in response to sustained hypercalcaemia. With an immunoperoxidase staining method for calcitonin, C-cell hyperplasia was noted in four of six cases of autosomal dominant polycystic kidney disease and in three of six cases of acquired renal cystic disease, an overall incidence of 58% compared with an incidence of 36% (five of 14) in cases of primary hyperparathyroidism with parathyroid adenoma. Thus, both primary and secondary hyperparathyroidism may trigger C-cell hyperplasia in an attempt to produce a hypocalcaemic effect.
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PMID:C-cell hyperplasia in secondary hyperparathyroidism. 145 30

We developed a sensitive and specific two-site radioimmunoassay (IRMA) for human osteocalcin using human osteocalcin as a standard and two monoclonal antibodies raised against human osteocalcin purified from human cortical bone, a solid-phase anti-25-37 region and a tracer anti-5-13 sequence of the molecule. A wide range of osteocalcin levels (up to 300 ng/ml) can be measured with a sensitivity of 0.4 ng/ml. The intra- and interassay coefficients of variation are less than 4 and 6%, respectively. The recovery of human osteocalcin from serum samples ranges from 96 to 103%. IRMA was linear for serial sample dilutions in a wide range of serum osteocalcin levels, even in patients with chronic renal failure on hemodialysis. Depletion of serum in intact osteocalcin demonstrated that IRMA detects, in addition to the intact peptide, a large N-terminal midregion fragment that represents about 50% of total osteocalcin levels in normals and patients with Paget's disease and up to 75% in patients with chronic renal failure. This large fragment, previously unrecognized because it cannot be distinguished from intact osteocalcin with gel filtration chromatography, is not generated in vitro by incubation of the serum up to 26 h. We measured osteocalcin in the serum of 309 healthy adults (180 men and 129 women, age range 20-95 years), 36 patients with Paget's disease, 12 patients with primary hyperparathyroidism, 70 patients with chronic renal failure on hemodialysis, and 10 patients on corticosteroid therapy, simultaneously with human IRMA and with a conventional radioimmunoassay (RIA) based on bovine reagents. A tight correlation (r = 0.889) was observed between the two assays in the normal population, but the values obtained with IRMA were about threefold higher (mean 23.3 +/- 10.5 versus 7.5 +/- 3.4 ng/ml) than those obtained with RIA. Reported as Z scores, that is, number of standard deviations from the predicted normal mean adjusted for sex and age, these two assays (IRMA and RIA) gave concordant results in patients with Paget's disease (4.05 +/- 6.21 versus 2.41 +/- 2.53), primary hyperparathyroidism (4.14 +/- 7.17 versus 2.13 +/- 2.28), chronic renal failure (25.32 +/- 24.49 versus 6.93 +/- 5.48), and glucocorticoid treatment (-1.48 +/- 0.78 versus -1.11 +/- 0.57). However, IRMA was more discriminant from controls for all these metabolic bone diseases because the absolute values of mean Z scores with IRMA were significantly higher than those obtained with the RIA (p < 0.05-0.0001).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Measurement of serum osteocalcin with a human-specific two-site immunoradiometric assay. 148 25

A patient with erosive spondyloarthropathy (ESA) and primary hyperparathyroidism is described. In the past, ESA has been described exclusively in patients with chronic renal failure (CRF) and has been attributed to crystal deposition, amyloidosis, severe secondary hyperparathyroidism, or other abnormalities of chronic renal failure. This patient with normal renal function suggests that secondary hyperparathyroidism plays the major pathogenetic role in ESA in patients with renal failure.
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PMID:Erosive spondyloarthropathy in primary hyperparathyroidism without renal failure. 162 86


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