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 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

The expression of parathyroid hormone-related protein (PTHrP) in abnormal human parathyroids was investigated. Northern blot analysis of RNA extracted from human benign parathyroid adenomata (n = 4) revealed multiple PTHrP mRNA species ranging in size from 1.8 to 4 kb. The relative abundance of PTHrP mRNA expressed in two of the adenomata was similar to that of a tumour (DAF) associated with humoral hypercalcaemia of malignancy, whereas PTHrP mRNA was of low abundance in a third and was undetectable in the fourth. PTHrP-like immunoreactivity was detected in extracts of abnormal parathyroid tissue (benign adenoma (n = 7), hyperplasia (n = 5) and parathyroid carcinoma (n = 2] using a sensitive specific two-site immunoradiometric assay for human (h) PTHrP(1-86) and a radioimmunoassay for hPTHrP(1-34). Ratios of hPTHrP(1-86)- and hPTHrP(1-34)-like immunoreactivities relative to hPTH(1-84)-like immunoreactivity in the parathyroid tissue extracts were, on average, less than 1%. PTHrP bioactivity in the extracts could not be distinguished from that of PTH, by an osteosarcoma cell bioassay. We conclude that, despite reports of over-expression of PTHrP mRNA in parathyroid adenomata, the potential contribution of PTHrP to the total PTH-like activity of adenomata and other abnormal parathyroid tissue may be insignificant relative to PTH.
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PMID:Expression of parathyroid hormone-related protein in abnormal human parathyroids. 206 98

In order to assess the correlation between menopause and osteoporosis, both in pathogenetic and therapeutical terms, a study was carried out in four comparable group of patients at Department B of the Institute of Gynaecology and Obstetrics at the University of Turin. Patients were divided as follows: 24 patents affected by evident osteoporosis, 39 patients with the first symptoms of osteoporosis, 27 with hypercalcemia and 33 healthy controls. The following tests were performed in all subjects: serum assay of androstenedione, estrone, 17-beta-estradiol, PTH, calcium, phosphorus, alkaline phosphatase and creatinine. Laboratory tests were repeated monthly in all patients and control subjects. Dual chromatic ray bone densitometry was performed in all patients at the start and end of treatment. With regard to therapy, each group was subdivided into two equal subgroups which were treated with carbocalcitonin or conjugated estrogens. From the findings, it is clear that there is a non-significant difference between serum levels of androstenedione, estrone and estradiol in the three groups examined and control subjects. Although the possibility that the fall in steroid hormones might contribute to bone load cannot be excluded, it is not possible to demonstrate that this is the most important factor in the pathogenesis of osteoporosis given that many women do not develop osteoporotic symptoms after menopause. In addition, in therapeutic terms, all bone density parameters considered in patient osteoporosis improved after therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Comparative analysis of therapeutic effects of carbocalcitonin and and conjugated estrogens in post-menopausal osteoporosis]. 208 96

Primary hyperparathyroidism can be caused by a solitary parathyroid adenoma and sometimes by hyperplastic parathyroid glands, multiple adenomas, or carcinoma. In the majority of patients, the diagnosis is made tentatively by chemistry profiles that show elevated serum calcium. It is confirmed by repeated serum calcium values and PTH determination. The parathyroid abnormality, if an adenoma, can usually be localized preoperatively by thallium-technetium scan, ultrasound, or computed tomography. In the case of persistent disease with hypercalcemia, an angiogram with selective venous sampling for PTH is helpful. At exploration, both sides of the neck may need exploration. A unilateral procedure may be sufficient, if the preoperative localization tests are confirmatory and if biopsy of another "normal" gland shows normal histologic findings. During the postoperative period, suction drains will lessen the likelihood of hematoma formation and serum calcium levels are monitored for the first 3 to 5 days. Symptomatic patients with low calcium levels receive intravenous and oral calcium supplements until values are brought to the low-normal range. Supplements are tapered as the calcium in the serum rises. The majority of patients who undergo parathyroid surgery will benefit both symptomatically and metabolically.
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PMID:Hyperparathyroidism. 211 Jun 44


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