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)

The aim of the study was to investigate the interrelation between induced hypercalcaemia and serum intact parathyroid hormone (S-PTH(1-84)) in normal man and in patients with primary hyperparathyroidism (PHPT) by measuring blood ionized calcium (B-Ca++) and S-PTH(1-84) before and during a controlled calcium infusion. Guided by frequent measurements of B-Ca++, we adjusted the calcium infusion rate continuously, thereby keeping B-Ca++ in a steady state at a pre-determined level approximately 0.25 mmol l-1 above baseline values. This calcium clamp technique (CCT) applied to 14 normal volunteers for 120 min established a standardized reference for parathyroid suppression and the renal physiological PTH response. The reproducibility of the method and the results obtained by the CCT were satisfactorily assessed in six of the 14 normal subjects. In normal subjects B-Ca++ was raised from 1.25 +/- 0.3 mmol l-1 (mean +/- SD) to 1.49 +/- 0.02 mmol l-1 suppressing S-PTH(1-84) to 264 +/- 9.9% of pre-infusion levels. We applied the CCT to 10 patients with PHPT for 120 min raising B-Ca++ from 1.41 +/- 0.09 mmol l-1 to 1.69 +/- 0.08 mmol l-1, thereby suppressing S-PTH(1-84) to 47.9 +/- 16.3% of pre-infusion levels. The renal handling of calcium and phosphate during CCT demonstrates the biological effects of suppressed activity of PTH on the renal tubules showing increments in the maximal tubular phosphate reabsorption in relation to the glomerular filtration rate (TmP/GFR) and decreased tubular reabsorption fraction of calcium. The described CCT is a safe and reliable dynamic test.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Calcium clamp technique: suppression of serum intact PTH by induced hypercalcaemia in normal man and primary hyperparathyroidism. 141 Dec 58

This investigation was carried out to evaluate the clinical utility and diagnostic value of serum intact PTH measurement using a recently introduced immunochemiluminometric assay (ICMA). Studies were carried out in 42 normal subjects, 24 patients with primary hyperparathyroidism, 21 patients on chronic maintenance hemodialysis, 8 patients with postsurgical hypoparathyroidism, 7 patients with cancer hypercalcemia and 6 patients with osteomalacia. A good correlation was found in normal subjects between serum ICMA PTH levels and both intact PTH measured by a two-site immunoradiometric assay (n = 42, r = 0.67, p less than 0.001) and a widely used midmolecule radioimmunoassay (n = 21, r = 0.78; p less than 0.001). Similar good correlations were found in primary hyperparathyroidism patients (IC-MA vs immunoradiometric assay r = 0.74; p less than 0.001; ICMA vs midmolecule assay r = 0.77; p less than 0.001). As far as the hypercalcemic conditions were concerned, in 5 patients with mild primary hyperparathyroidism, ICMA PTH levels were in the upper range of those found in normal subjects, even though they were inappropriately high in respect to serum calcium values. However, serum ICMA PTH levels were clearly suppressed or undetectable in the majority of patients with cancer hypercalcemia or postsurgical hypoparathyroidism. Following calcium and EDTA infusions in patients with primary hyperparathyroidism, the behaviour of ICMA PTH levels in general parallelled that of immunoradiometric PTH assay, thus indirectly suggesting the ability of the method to measure the intact molecule.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Conventional and new diagnostic applications of a two-site immunochemiluminometric assay for parathyroid hormone. 144 86

Pamidronate (aminopropylidene diphosphonate, APD) is known to be an effective agent in lowering plasma calcium in cancer associated hypercalcaemia and in primary hyperparathyroidism. Combined therapy with pamidronate and calcitonin has proved efficient in the treatment of severe cancer-associated hypercalcaemia. A 66-year-old woman in hypercalcaemic crisis caused by primary hypreparathyroidism was successfully treated with this combined therapy. Albumin corrected plasma calcium was 5.26 mmol/l on arrival and the PTH level was very high. The combined therapy lowered the plasma calcium to normal and made it possible to perform elective parathyreoidectomy. A 5.8 g parathyroid adenoma was removed. It is recommended to consider combined therapy with pamidronate and calcitonin in the emergency management of hypercalcaemic crisis.
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PMID:[Combination therapy with pamidronate and calcitonin in hypercalcemic crisis caused by primary hyperparathyroidism]. 146 41

Hypercalcemia may occur as a complication of haematological malignancies, in association with solid tumors with bone metastases, and with solid tumors in the absence of bone metastases. The latter syndrome, known as the humoral hypercalcemia of malignancy (HHM) shares many features with primary hyperparathyroidism. A parathyroid hormone-related protein (PTHrP) has been identified, isolated and cloned, which is most likely responsible for the calcium disturbances in HHM, PTHrP is a previously unrecognized hormone which has limited amino-terminal sequence homology with PTH and is the product of a separate gene. Tissue localization studies have identified PTHrP in squamous cell carcinomata, renal cortical carcinomata, in a proportion of breast cancers and in adult T-cell leukemia/lymphoma. In normal tissues, PTHrP has been immunohistochemically localized in keratinocytes, placenta and fetal parathyroid glands. In addition to its role in mediating hypercalcemia in cancer, PTHrP is likely to have an important endocrine role in the fetus, and perhaps a paracrine function in several organs.
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PMID:Hypercalcemia in cancer. 152 53

Parathyroid carcinoma is a rare tumor responsible for 0.5-5% of primary hyperparathyroidism. It is usually small (not more than 27 g) and the precise diagnosis of malignancy is made when local or distant metastases are found. We describe a case of a 37 yr old male presenting with a substernal goiter and no specific symptoms except hypertension. This mass had cysts and calcifications and it was in the anterior upper mediastinum. The patient had severe hypercalcemia (Ca greater than 14 mg/dl), high PTH levels and mild renal failure. Bone scanning showed signs of hyperparathyroidism. The patient was subjected to total thyroidectomy and removal of the mass en block. The tumor was circumscribed lobulated and mostly cystic. It weighed 1,200 g (380 g after evacuation of cysts) and measured 12 x 9 x 4.5 cm. Histologic examination showed a highly differentiated adenocarcinoma of parathyroid with metastasis in a regional lymph node. Almost 4 years later the patient is alive and well without hypercalcemia and without evidence of distant metastases.
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PMID:Large parathyroid functioning carcinoma (1,200 g) presenting as a substernal goiter. 156 Jan 89

We report a family with primary hyperparathyroidism in four patients in two generations with apparent autosomal dominant transmission. A fifth member was probably affected. Two cases had definite parathyroid carcinoma (PC), and two had parathyroid adenoma with atypical features that could represent an early stage of cancer. In each of our patients, one parathyroid gland was abnormal. Five other parathyroid glands (in two patients) were normal in histology and size. There was no evidence of neoplasia in other tissues. Constitutional karyotypes were normal in all four patients. We identified three chromosomal abnormalities (a reciprocal translocation between chromosomes 3 and 4, trisomy 7, and a pericentric inversion in chromosome 9) in cultured PC tissue from one patient. These chromosomal changes are of unclear significance. Analyses on tumor DNA from one case of PC and one of atypical adenoma showed no evidence of ras gene mutations, PTH gene rearrangement, or allelic loss from chromosome 11q13 (locus of the gene for multiple endocrine neoplasia type 1). This family shows susceptibility to cancer without antecedent hyperplasia in all parathyroids. It could help identify a novel tumor susceptibility gene.
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PMID:Studies in a kindred with parathyroid carcinoma. 163 36

Among 1819 patients with renal stone disease 44 cases with primary hyperparathyroidism (p.h.p.) were diagnosed. In all cases the diagnosis of php was confirmed by histomorphological examination. In 34 patients with php solitary adenoma was found, in 5 patients an adenoma with concomitant hyperplasia of the parathyroid glands, in 2 patients hyperplasia and in 3 patients carcinoma of the parathyroid glands. Hypercalcemia was found in 86% of patients, while elevated plasma levels of PTH in 90% of patients with php. Not in all patients PTH secretion was entirely autonomous. No significant correlation was found between plasma levels of PTH and kind of pathology of the parathyroid glands as well as clinical feature of php respectively.
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PMID:[Hypercalciuria and primary hyperparathyroidism in patients with kidney calculi. II. Primary hyperparathyroidism]. 164 64

The performance and clinical utility of an automated assay of intact parathyroid hormone (parathyrin, PTH) are evaluated. The method is based on the extraction of PTH from plasma by an HPLC column containing immobilized anti-(44-68 PTH) antibodies. The PTH retained is detected with a postcolumn reactor and use of anti-(1-34 PTH) chemiluminescent-labeled antibodies. The total cycle time of the assay is 6.5 min per injection after a 1-h incubation. The lower limit of detection for PTH in a 66-microL plasma sample was 0.5 pmol/L based on peak heights and 0.2 pmol/L based on peak areas. Mean analytical recovery for PTH added to plasma was 97%. The within-day precisions (CVs) for 4.2 and 30 pmol/L PTH plasma samples were 9.2% and 5.6% and the day-to-day precisions were 10.3% and 5.7%, respectively. No significant interferences from 1-34, 44-68, or 53-84 PTH fragments were noted, even at highly increased concentrations of fragments. The correlation of results with those of a manual assay of intact PTH was 0.97, and the results showed good agreement with disease state for patients with hypo- or hyperparathyroidism. The specificity of the assay for primary hyperparathyroidism was greater than 95%. We discuss the advantages (speed and quality control) of this approach over current immunoassays and the potential use of this method for detecting other analytes.
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PMID:Intact parathyroid hormone: performance and clinical utility of an automated assay based on high-performance immunoaffinity chromatography and chemiluminescence detection. 164 22

Plasma concentrations of PTH are much lower for a given calcium or phosphorus level in patients with familial benign hypercalcemia (FBH, or familial hypocalciuric hypercalcemia) than in those with primary hyperparathyroidism; these and other data suggest that there might be tissue hypersensitivity to PTH in FBH. To test this hypothesis, we have used cultured dermal fibroblasts from abdominal skin biopsies of six patients with FBH and six age- and sex-matched controls as surrogate PTH-responsive tissues. Cells in 24-well plastic plates were exposed to vehicle, human PTH-(1-34) (10(-10)-10(-7) M), prostaglandin E2 (10(-6) M), or isoproterenol (10(-4) M) for 10 min in the presence of isobutylmethylxanthine, and cellular cAMP was determined by RIA. All cells responded to PTH with dose-dependent increases in cAMP, and all responded strongly to prostaglandin E2 and isoproterenol. There were no consistent or significant differences between control and FBH fibroblasts in maximal responses to the three agonists, and half-maximal stimulation was achieved with about 10(-9) M PTH in both normal and FBH cells. These data are not consistent with increased tissue sensitivity to PTH in FBH.
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PMID:Cyclic adenosine 3',5'-monophosphate responses to parathyroid hormone, prostaglandin E2, and isoproterenol in dermal fibroblasts from patients with familial benign hypercalcemia. 171 Jun 22

The two most frequent causes for hypercalcemia are primary hyperparathyroidism and hypercalcemia associated with malignancy. Elevated or inappropriately high PTH serum levels are the hallmark of hyperparathyroidism. Sensitive immunometric assays for the secreted, biologically active, intact parathyroid hormone molecule, PTH-(1-84), employ two populations of region-specific antibodies, take advantage of saturation kinetics rather than competitive binding, and have many technical advantages over conventional radioimmunoassay. Approximately 90% of patients with primary hyperparathyroidism have elevated serum levels of PTH-(1-84) by immunometric assay; the remainder have inappropriately elevated values of PTH for the serum calcium concentration. Clinical correlation studies comparing measurements of PTH using antisera that recognize the carboxyl, midregion, or amino terminus of PTH with PTH levels determined by immunometric assays demonstrate elevated values in equivalent numbers of hyperparathyroid individuals. Immunometric assays for PTH-(1-84) have their greatest value in separating patients with hyperparathyroidism from those with hypercalcemia of malignancy. In earlier studies using region-specific antisera, there was virtually always an overlap of serum PTH levels in hyperparathyroidism and hypercalcemia associated with malignancy. In contrast, analysis of results using PTH-(1-84) immunometric assays in several hundred reported patients shows a complete separation of PTH values. Clinical judgment, combined with measurement of PTH in the setting of hypercalcemia, can lead to the diagnosis of hyperparathyroidism with confidence in essentially all patients.
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PMID:Immunoassays for parathyroid hormone 1-84 in the diagnosis of hyperparathyroidism. 172 83


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