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)

In patients with either Paget's disease or hypercalcaemia associated with malignancy (HCM) we have assessed the parathyroid response to pamidronate therapy, both by immunoassay of serum intact parathyroid hormone PTH (1-84) and by measurement of indirect parameters of PTH bioactivity, tubular maximum reabsorption of phosphate (TmPO4/GFR) and nephrogenous cyclic AMP (NcAMP). In 12 patients with Paget's disease, therapy with pamidronate produced a small but significant decrease in adjusted serum calcium within the reference interval which was accompanied by a progressive increase in PTH (1-84) secretion and a corresponding fall in TmPO4/GFR and increase in NcAMP. In 12 patients with HCM pretreatment, PTH (1-84) concentrations were suppressed, whilst mean TmPO4/GFR was reduced and NcAMP was increased, compatible in most patients, with parathyroid hormone-related peptide (PTHrP) driven hypercalcaemia. Therapy with pamidronate produced the expected fall in serum calcium but caused an increase in PTH (1-84) secretion in the presence of absolute hypercalcaemia. The initial subnormal TmPO4/GFR decreased further to a nadir on day 5, and there was a corresponding further increase in NcAMP. By day 7, however, when PTH (1-84) concentrations were maximal, there was a significant paradoxical rise in TmPO4/GFR and a corresponding decrease in NcAMP. These data are consistent with a variable trigger point for PTH (1-84) secretion, one consequence of which is a reduction in the risk of hypocalcaemia following pamidronate. The results have major clinical implications for the interpretation of PTH (1-84) measurements in patients who are being treated or about to be treated for bone disease or for hypercalcaemia of malignancy (HCM).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Direct and indirect assessment of the parathyroid hormone response to pamidronate therapy in Paget's disease of bone and hypercalcaemia of malignancy. 184 62

The biological properties of a new synthetic analog of parathyroid hormone-related protein [PTHrP-(7-34)NH2] were examined in vivo using a well characterized thyroparathyroidectomized (TPTX) rat model. The phosphaturic and urine cyclic AMP response induced by infusion of PTHrP-(1-34)NH2 (0.16 nmol/h) was inhibited by 70% (P less than 0.01, n = 6) by co-infusion of PTHrP-(7-34)NH2 at a 10-fold molar excess (1.6 nmol/h). The 7-34 PTHrP analog also antagonized the PTHrP-(1-34)NH2-induced hypercalcemia and rises in blood 1,25-dihydroxyvitamin D concentrations. However, when infused alone at a higher dose rate (8 nmol/h), PTHrP-(7-34)NH2 displayed significant PTH agonist activity. This profile contrasts to that of [Tyr-34]bPTH-(7-34)NH2 which is comparatively less potent (10-20-fold) with respect to its antagonist activity but has no appreciable agonist activity in vivo.
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PMID:A 7-34 analog of the parathyroid hormone-related protein has potent antagonist and partial agonist activity in vivo. 185 Jun 33

We have used an immunoradiometric assay (IRMA) to measure intact PTH. The serum-levels of PTH followed a log-normal distribution in a population of 85 healthy post-menopausal women, with a geometric mean of 1.9 pmol/l and a range of 0.8-6.1 pmol/l. The correlation between measurements performed using the IRMA and a radioimmunoassay which measured the C-terminal portion of the PTH molecule was 0.85. It was only the IRMA, however, that could measure subnormal values. Two of 27 patients with primary hyperparathyroidism had PTH-values in the upper reference interval. The rest of the patients had elevated levels. Patients with hypercalcemia due to malignancy had subnormal or low normal (less than 2.5 pmol/l) PTH values. Half of the patients with hypoparathyroidism had PTH below the limit of detection. Four subjects with familial hypercalciuric hypercalcemia had normal (3) or slightly elevated PTH-levels.
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PMID:[Determination of intact parathyroid hormone in patients with calcium metabolism disorders]. 185 14

We report the development of a two-site immunoradiometric assay for PTH(1-84) based on two site-specific monoclonal antibodies--3B3 (radiolabelled antibody) specific for PTH(1-34) and ESQ1 (on solid phase) specific for PTH(74-84). Antibody 3B3 is sensitive to the oxidation of the methionine residues in PTH(1-34) therefore hydrogen peroxide (0.1 M) is added to the incubation mixture. Validation studies confirm quantitative recovery of both oxidized and reduced PTH(1-84). The assay has a minimum detection limit of 0.5 pmol/L and a range of 1.5-250 pmol/L with an intra-assay CV of less than 10% (2.8-250 pmol/L less than 5% CV). Studies on clinical samples indicate good discrimination between normal subjects (mean 2.21; range 1.0-5.0 pmol/L) and patients with primary hyperparathyroidism (mean 21.0; range 5.8-100 pmol/L) who in turn are well separated from patients with hypercalcaemia of malignancy (14/18 less than 0.5 pmol/L).
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PMID:A two-site immunoradiometric assay for PTH(1-84) using N and C terminal specific monoclonal antibodies. 185 54

The coexistence of hyperparathyroidism complicating thyrotoxicosis is quite rare. We report the case of one patient who presented with thyrotoxicosis, (total thyroxine of 15.1 micrograms/dl (5-13), free thyroxine index of 18 (4-15) and triiodothyronine by RIA of 305 ng/dl (70-230) and asymptomatic hypercalcemia of 15 mg/dl (8.5-10.6), who was also initially noted to have an elevated (C-terminal) serum immunoreactive parathyroid hormone (iPTH) level of 8,800 pg/ml (50-340). With propylthiouracil and propranolol, however, this patient became normocalcemic with a decrease in iPTH values to 714 pg/ml. As the patient was tapered from medication, after being rendered euthyroid, a recurrence of hypercalcemia with rising iPTH levels occurred. PTH levels should be helpful in defining coexisting hyperparathyroidism in patients with thyrotoxicosis since in the latter iPTH is usually suppressed. Our findings support the recommendation that in patients suspected of having both hyperparathyroidism and hyperthyroidism, a diagnosis of the former can only be made with certainty after the patient has been rendered euthyroid with persistently elevated serum calcium and iPTH levels. While there are no clinical features which permit the easy identification of patients who present with dual lesions, the determination of iPTH values may be the most consistently helpful test initially, whereas other parameters such as vitamin D, serum phosphate are less reliable.
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PMID:Coexisting hyperparathyroidism with thyrotoxicosis. 186 80

A 63 year-old male, who was first diagnosed as primary macroglobulinemia (IgM-kappa type) developed non-Hodgkin's lymphoma after 10 month clinical course. He had huge, multiple intrahepatic nodular lesions and had consciousness disturbance due to marked hypercalcemia. Since the treatment with gluco-corticoid and calcitonin was not effective for the improvement of patient's general condition, calcium-free hemodialysis was performed. After 2-hour dialysis, serum-Ca level was decreased from 15. 2mg/dl to 10.0mg/dl. Histology of the aspiration biopsy specimen obtained from the liver showed malignant lymphoma, diffuse, large cell type (B cell origin). Combined chemotherapy (CHOP) was started and was quite effective not only for the regression of the primary lesions but also for the normalization of the serum-Ca level. The existence of PTH-like substance produced by the tumor cell was suspected and may be related to the hypercalcemia in this case. Finally, our results demonstrated that calcium-free hemodialysis is safe and highly effective for the management of hypercalcemia caused by malignancy.
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PMID:[Successful treatment of non-Hodgkin's lymphoma with consciousness disturbance due to hypercalcemia by the calcium-free hemodialysis and combined chemotherapy]. 187 Feb 72

Malignancy is the most frequent cause of hypercalcemia in hospitalized patients. The pathophysiology of hypercalcemia of malignancy (HM) is complex. Increased bone resorption is involved in most cases caused either by extensive local bone destruction or by humoral factors. Tumor extracts from patients with humoral hypercalcemia of malignancy (HHM) often contain PTH-like bioactivity. Recently, cDNAs coding for a PTH-related protein (PTH-rP) has been cloned. The N-terminal amino acid sequence of this protein shows a considerable homology with human PTH. However, other bone resorbing factors including prostaglandins, transforming growth factors, colony stimulating factors, leucocyte cytokines and 1,25-dihydroxyvitamin D may be involved in different types of malignancy. HM is usually progressive with troublesome symptoms and a high mortality. Several treatment alternatives are available including rehydration, bisphosphonates, calcitonin, plicamycin, phosphate, and glucocorticoids. Others are under investigation. Treatment should be individualized taking into account the pathophysiological mechanisms involved, the extent of hypercalcemia and renal failure, and the prognosis related to the malignant disease.
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PMID:Hypercalcemia of malignancy: pathophysiology, diagnosis and treatment. 188 26

A 40-year-old woman was admitted because of long-lasting asymptomatic hypercalcaemia. About 2 years earlier she underwent thyroidectomy and further 131 I therapy because of well-differentiated non medullary thyroid carcinoma. On admission biochemical data and hormonal values (serum calcium, serum phosphorus, i-PTH) were consistent with primary hyperparathyroidism; ultrasonography, computed tomography, thallium-technetium scintiscanning disclosed right paratracheal mass; on surgical procedure a right parathyroid adenoma was removed. The coexistence of non medullary thyroid carcinoma and primary hyperparathyroidism is rare: the prior 131 I therapy might be linked to subsequent development of parathyroid adenoma.
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PMID:An association of primary hyperparathyroidism and non medullary thyroid carcinoma. 188 51

A 74-year-old male was urgently admitted to our hospital because of consciousness disturbance. Laboratory data showed remarkable hypercalcemia (7.8 mEq/L), hypophosphatemia, low % TRP, low intact PTH level, normal nephrogenic cyclic AMP and normal 1,25 (OH)2D level. Serum bone Gla protein, which was thought to express osteoblastic activity, was low. Serum tartarate resistant acid phosphatase and urinary excretion of hydroxyproline, which were thought to express osteoclastic activity, were high. CT scan showed an enlarged mass in the left renal pelvis, which was found to be a squamous cell carcinoma (SCC) by biopsy through percutaneous nephroscopy. Bone scintigram appeared normal. Therefore, we diagnosed it as renal pelvic SCC with humoral hypercalcemia of malignancy (HHM) and performed left nephrectomy. After nephrectomy, serum calcium returned to normal. But after a few weeks, lung metastasis appeared and serum calcium was reelevated. As to PTH related protein (PTHrP) which was thought to induce HHM, PTHrP content of the resected tumor measured by RIA assay was 13 pmol/g wet weight of tissue, which suggested that this tumor might have been producing PTHrP.
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PMID:[A case of renal pelvic squamous cell carcinoma accompanied with humoral hypercalcemia of malignancy]. 192 Oct 23

Fourteen patients with chronic renal failure and secondary hyperparathyroidism were treated by subtotal parathyroidectomy. Bone pain and hypercalcemia were the main indications to surgery respectively in 13 and 1 patients. Bone pain disappeared or was significantly reduced in 12/14 patients. Two patients had a persistent hyperparathyroidism. Serum alkaline phosphatase returned to normal in 12 patients and PTH in 11 of 12 patients with pretreatment high levels.
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PMID:[Secondary hyperparathyroidism in chronic renal failure. Role of subtotal parathyroidectomy]. 192 66


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