Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A RIA for PTH-related protein (PTHrP) is described, using a polyclonal goat antiserum against synthetic PTHrP-(1-40) and recombinant PTHrP-(1-84) as standard. The detection limit is 2 pmol/L, and intra- and interassay coefficients of variation are 4.8% and 13.6%, respectively. This assay does not detect PTH even at concentrations of up to 2000 pmol/L. Cross-reactivity studies using various synthetic PTHrP peptides localize the antibody-binding epitope between residues 20 and 29. Hypercalcemic patients with a range of solid tumors and no evidence of bone metastases on radionuclide scanning (n = 27) all had detectable PTHrP levels (range, 2.8-51.2 pmol/L). Of 17 patients with solid tumors (other than breast) and bone metastases, 11 (64%) also had detectable PTHrP levels (range, 4.9-47.5 pmol/L). Twenty samples from breast cancer patients with hypercalcemia, 19 with evidence of bone metastases, and 1 with a negative bone scan were assayed, and detectable PTHrP levels were found in 13 (65%; range, 3.8-61.6 pmol/L). Patients with squamous cell carcinomata and normal serum calcium levels (n = 11) had no detectable PTHrP or levels close to the detection limit of the assay (range, less than 2 to 3.7 pmol/L). Plasma levels in normal volunteers were below the detection limit of the assay in all but 1 of 38 normal subjects. Patients with chronic renal failure on hemodialysis (n = 18) and patients with primary hyperparathyroidism (n = 14) all had undetectable PTHrP in this assay. This assay allows positive identification of patients with PTHrP-mediated hypercalcemia and, therefore, should be useful in the clinical investigation of the hypercalcemic patient. Furthermore, it has allowed detection of circulating PTHrP in hypercalcemic breast cancer patients with bone metastases, indicating a significant role for PTHrP in this disease.
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PMID:Parathyroid hormone-related protein: elevated levels in both humoral hypercalcemia of malignancy and hypercalcemia complicating metastatic breast cancer. 195 13

The mechanisms of hypercalcaemia were assessed in 20 hypercalcaemic patients with breast cancer. Abnormalities suggestive of a PTH-related peptide (PTHrP) mechanism were observed in up to 60% of cases; urinary cyclic adenosine monophosphate (UcAMP) was elevated in nine patients (45%), renal tubular reabsorption of calcium (RTRCa) was elevated in nine (45%) and the renal tubular threshold for phosphate reabsorption (TmPO4) depressed in 12 (60%). While TmPO4 was lower in patients with high UcAMP, there was no consistent relationship between RTRCa and UcAMP or UcAMP and the extent of bone metastases. In a control group of nine normocalcaemic breast cancer patients, bone resorption as assessed by urinary calcium/creatinine ratio was slightly increased but UcAMP, RTRCa and TmPO4 were generally normal. These observations indicate that a PTHrP-mediated mechanism of hypercalcaemia may be operative in up to 60% of patients with breast cancer, irrespective of the presence or extent of bone metastases.
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PMID:Breast cancer-associated hypercalcaemia: a reassessment of renal calcium and phosphate handling. 196 70

Secondary hyperparathyroidism (HP) is well known complication of long-term uremia. CAPD patients show a peculiar behaviour due to loss of vitamin D metabolites through peritoneum. Severe degrees of hyperparathyroidism may require parathyroidectomy in order to achieve appropriate control. Recently, the possibility of controlling this situation with high oral doses of calcitriol has been communicated. The purpose of this study is to evaluate the effect of this agent on hyperparathyroidism in CAPD patients. Two different groups were constituted according to the length of time on dialysis when HP was detected. All of the patients had i-PTH serum levels five times higher than the normal values (50 pg/ml). During a six month period the daily dose of oral calcitriol was increased in order to achieve a reduction in i-PTH level. The results after this period showed a significant reduction in i-PTH levels (614 +/- 378 to 241 +/- 80 pg/ml) with an average increase in oral calcitriol from 0.16 +/- 0.1 to 0.67 +/- 0.4 with no significant changes in serum calcium or phosphorus. The group with HP at start of dialysis achieved these effects easier and with lower doses of calcitriol. We conclude that moderately high doses of oral calcitriol control secondary hyperparathyroidism in CAPD patients without hypercalcemia.
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PMID:Secondary hyperparathyroidism in CAPD patients: its suppressibility with high doses of calcitriol. 198 16

A variety of tumors and nontumorous lesions were used to illustrate some of the biologic, clinical, and pathologic aspects of inappropriate or ectopic endocrine and metabolic syndromes that have musculoskeletal repercussions. It is clear, both from the discussion and case material, that many mechanisms of ectopic endocrine syndromes have yet to be clarified. Elaborate techniques are available for hormonal estimations, but their routine use is prohibitively expensive and relatively unrewarding. Cells of a given lesion may be functionally heterogeneous or may fail to elaborate active products in substantial amounts. Different cells may produce similar peptides, while the same cells can produce more than one. Despite these difficulties, recognition of ectopic endocrine syndromes remains crucial to diagnosis and patient management, and thus corroboration or correlation must often rest on a cruder basis. In fact, the clinical significance of basic laboratory data, e.g., PTH elevation, may vary, as PTH may be immunoreactive but biologically inactive. As another example, hypercalcemia associated with myeloma may be variously related to coexistent hyperparathyroidism, renal disease, dehydration, or humoral osteolysis. Therefore, roentgenographic evidence of bone destruction or skeletal stigmata of hyperparathyroidism imbues laboratory data with greater significance. Paraneoplastic syndromes are of particular concern to the radiologist, as multiple systemic manifestations, occurring either synchronously or metachronously, may suggest the presence of an underlying or unifying lesion or even of a specific type of neoplasm. They may precede detection of neoplasms by months to years and can develop at any time during their course. Paraneoplastic syndromes may, furthermore, parallel the course of a lesion and be used as indicators of remission or recurrence. Conversely, those unassociated with overt symptoms possess endocrine markers that can reinforce sometimes silent skeletal stigmata. Familiarity with representative secretory products influencing the musculoskeletal system per se may often clarify seemingly innocuous and sometimes asymptomatic skeletal findings. Alert imagers may, therefore, detect, infer, or suspect particular syndromes when they present in a specific sequence or mosaic. Conversely, when apprised of their existence, imagers should know where their related effects may be sought or anticipated. Such relationships, sometimes serendipitously discovered, may be valuable assets in clinical diagnosis and patient management in both suspected and unsuspected cases.
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PMID:Skeletal manifestations of ectopic or inappropriate endocrine and metabolic syndromes. 198 23

Parathyrin (parathyroid hormone; PTH) was measured with three immunoassays: a two-site immunochemiluminometric (ICMA) and a two-site immunoradiometric (IRMA) method for intact PTH, and a sensitive radioimmunoassay for mid-region or "total" PTH, measuring both intact hormone and inactive fragments. Single specimens from normal subjects and from individuals with primary hyperparathyroidism, hypercalcemia associated with malignancy, and hypoparathyroidism were analyzed with all three methods. All individuals with primary hyperparathyroidism showed absolutely above-normal concentrations with the mid-region RIA, 28 of 29 did with the ICMA, and 21 of 29 did with the IRMA. PTH concentrations in primary hyperparathyroidism were most increased relative to normal subjects with the mid-region assay (10.4 times), less so with the intact assays (ICMA 5.5 times; IRMA 5.3 times). Concentrations of intact PTH were suppressed below normal in nearly all patients with hypercalcemia associated with malignancy, as measured with the ICMA (26 of 30) and the IRMA (28 of 30) assays. In marked contrast, results for mid-region PTH were normal or slightly above normal, consistent with studies suggesting that the parathyroids secrete both intact hormone and inactive fragments, the former being more sensitive to suppression by hypercalcemia. In hypoparathyroidism PTH concentrations were detectable but below normal in all patients by the intact assays and in all but one patient by the mid-region assay. These low concentrations are probably due to a nonspecific serum effect that could be resolved with selection of a more appropriate standard matrix. Although all three assays are useful in the differential diagnosis of hypercalcemia, two-site intact assays are more convenient and more specific in patients with compromised renal function.
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PMID:Immunochemiluminometric and immunoradiometric determinations of intact and total immunoreactive parathyrin: performance in the differential diagnosis of hypercalcemia and hypoparathyroidism. 199 16

The cause of hypercalcemia in familial benign hypercalcemia (FBH; also called familial hypocalciuric hypercalcemia) is unclear, although it is PTH dependent. It is also uncertain how plasma PTH levels are related to the severity of biochemical abnormalities in FBH. Because the PTH-related peptide (PTHrP) has many PTH-like actions, it might have a role in the hypercalcemia of FBH. Thus, we studied 29 patients with FBH from 11 families, 29 age- and sex-matched controls, and 42 patients with primary hyperparathyroidism (1 degree HPT), measuring PTH with a highly sensitive two-site immunochemiluminometric assay and the hypercalcemic tumor factor PTH-related peptide (PTHrP) with an extraction/concentration RIA. Plasma PTH values were elevated in 86% of 1 degree HPT patients (36 of 42), but in only 20% of FBH patients, (6 of 29). Plasma PTHrP was elevated in 1 FBH patient, and the group mean value was normal. Plasma PTH was positively correlated with calcium (Ca) in 1 degree HPT (r = 0.66; P less than 0.0001) and in FBH (r = 0.53; P less than 0.004), but the slopes of the regressions were markedly different: 1 degree HPT, 6.72; FBH, 1.61 (P less than 0.0001). There was a negative correlation between PTH and phosphorus (P) in 1 degree HPT (r = -0.39; P less than 0.01) and in FBH (r = -0.41; P less than 0.03), but, again, the slopes differed greatly: 1 degree HPT, -6.57; FBH, -1.95 (P less than 0.0001). There were no correlations between PTHrP and Ca or between PTH and PTHrP. The sums and products of PTH and PTHrP were not better correlated with Ca than PTH alone. Thus, PTH values are lower at given Ca and P levels in patients with FBH than in those with 1 degree HPT, suggesting that PTH is more effective in raising Ca and lowering P in FBH than in 1 degree HPT. The enigma of FBH remains: what molecular defect can simultaneously cause parathyroid cell insensitivity to Ca, enhanced renal tubular reabsorption of Ca, increased renal rejection of P, and enhanced or retained sensitivity to PTH?
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PMID:Plasma intact parathyroid hormone (PTH) and PTH-related peptide in familial benign hypercalcemia: greater responsiveness to endogenous PTH than in primary hyperparathyroidism. 199 10

Monoclonal and polyclonal antibodies recognizing human parathyroid hormone-like protein (PTHLP) have been produced using a series of recombinant and synthetic PTHLP peptides. These antibodies have been used to develop a two-site immunometric enzyme immunoassay which detects PTHLP[1-87] and PTHLP[1-141] but not PTH. The immunoassay detected PTHLP in extracts of squamous carcinomas and normal tissues at concentrations from 7-515 ng PTHLP[1-87]/mg protein. Immunoblotting of the extract which showed the highest immunoreactivity, a squamous carcinoma of the lung from a patient with hypercalcemia, revealed a major band having an apparent mol wt of 26,500 and several other higher mol wt bands. Similar polypeptides were observed by immunoblotting cell extracts from a cell line, SCaBER, which secretes immunoreactive PTHLP into its medium and also from tumors in nude mice derived from this cell line. Chaotropic agents did not alter the immunoblotting pattern, and antibodies to three different epitopes of PTHLP recognized these bands, indicating PTHLP expression in the extracts. Immunohistochemical staining of normal human tissue with these antibodies revealed several PTHLP-containing tissues and confirmed the results of the immunoassay, suggesting a paracrine role for PTHLP. Staining was observed in several neoplastic tissues including squamous cell carcinomas, lung carcinoma, bladder carcinoma, osteogenic sarcoma, and adenocarcinoma of the colon.
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PMID:Immunological identification and distribution of parathyroid hormone-like protein polypeptides in normal and malignant tissues. 200 11

Serum total, ultrafiltrable and protein-bound magnesium, and urinary fractional excretion of magnesium were studied in patients with primary hyperparathyroidism (before and after surgery) and in patients with hyperparathyroidism, malignant hypercalcemia and chronic renal failure with or without hemodialysis. Whereas serum total Mg was unchanged in patients with primary hyperparathyroidism, the ultrafiltrable magnesium concentration was higher than in the control group and higher before than after surgery. The total and the ultrafiltrable magnesium concentrations were highly correlated in the overall patients with Ca-related metabolic disorders, suggesting that renal function had no influence on the relation between these two parameters. Moreover, in malignant hypercalcemia, our results suggested that PTH-like peptides might be less effective than PTH in renal handling of Mg as previously described for Ca.
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PMID:Total and ultrafiltrable plasma magnesium in hyper- and hypoparathyroidism, and in calcium-related metabolic disorders. 202 73

46-year-old male patient was born in Niigata Prefecture and thereafter lived in Tokyo. In late January 1985, he noticed swelling of the bilateral inguinal lymph-nodes followed by fever and lumbago. In February, he consulted a local doctor and hepatosplenomegaly, marked leukocytosis and renal dysfunction were pointed out and he was referred to our hospital on February 22nd. The clinical laboratory data on admission were as follows; WBC 23,200/microliter, serum-Ca 18.4 mg/dl, BUN 85.3 mg/dl, creatinine 5.4 mg/dl, antibody to ATLV x160. ATL was diagnosed by biopsy of lymph nodes and examinations of peripheral blood and bone marrow hemogram. Remission was achieved in March by the treatment with adriacin. Renal failure and hypercalcemia also improved. However his respiratory dysfunction gradually worsened. The chest radiographies++ showed pulmonary edema, although there was no clinical evidence of heart failure. When his condition became stable, TBLB was performed and revealed extensive deposition of calcium along alveolar septae, suggesting that pulmonary edema was induced by the metastatic calcification of the lung. After the second treatment for ATL, he died of pneumonia. The autopsy showed calcium deposition not only in the lung but in pyramids of the kidney and in sub-serous layer of the small intestine. There was no tumor cell invasion into the bone or parathyroid gland. High urinary c-AMP together with normal levels of PTH suggested that the hypercalcemia in this case was induced by PTH-related protein. It was concluded that careful treatment for hypercalcemia is important as regards the occurrence of pulmonary edema.
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PMID:[An autopsy case of adult T-cell leukemia complicated with metastatic calcification of the lung]. 204 Dec 50

PTH and calcitonin are the two major hormones controlling calcium metabolism. Recently two new substances related to these hormones have been isolated: calcitonin gene related peptide (CGRP) and PTH-related protein (PTHrP). CGRP is a potent vasodilator and stimulant of intestinal secretion while PTHrP is probably the agent responsible for humoral hypercalcaemia of malignancy. We report here a patient with a prostatic tumour presenting with vasodilation, diarrhoea and hypercalcaemia. Our investigations revealed that the primary prostatic and liver secondary tumour contained CGRP, calcitonin and PTHrP. Most of the immunoreactive CGRP in the tumour and plasma co-eluted with the biologically active form of CGRP. The circulating levels of CGRP correlated with the presence of the diarrhoea. PTHrP concentration in the tumours was one of the highest reported for any tumour although previous studies may have utilized less than optimal extraction procedures. The somatostatin analogue, octreotide (SMS 201-995), did not reduce the plasma CGRP or the diarrhoea, a finding similar to that seen in patients with medullary thyroid carcinoma and high plasma CGRP. The hypercalcaemia was also unaffected by octreotide administration. This is the first report of a prostatic tumour associated with over-production of calcitonin, PTHrP and CGRP. The major life-threatening effects of this unusual case of prostatic carcinoma were diarrhoea and hypercalcaemia. Both these effects could be tentatively ascribed to newly discovered substances, CGRP and PTHrP. With the greater availability of assays to measure CGRP and PTHrP in plasma, a detailed examination of the incidence of over-production of these substances in various cancers will be possible.
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PMID:Production of calcitonin gene related peptide, calcitonin and PTH-related protein by a prostatic adenocarcinoma. 206 Jan 48


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