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)

Parathyroid hormone radioimmunoassay (RIA), specific for mid-region of the PTH molecule, has been proven to be extremely useful for the differential diagnosis of abnormal calcium metabolism. Recently, we developed a highly sensitive RIA for PTH, consisting of PTH antiserum (CH9), 125I labelled Tyr42 hPTH (43-68) and synthetic hPTH (1-84) as standard. This RIA cross-reacted with mid-region and carboxyl terminals of PTH. The within-assay and between-assay coefficients of variation were less than 4.6% and less than 8.6%, respectively. The limit of detection was 50pg/ml. The levels of serum calcium, serum phosphate, serum creatinine, Tmpo4/GFR and creatinine clearance (Ccr) in normal healthy volunteers aged 20 to 50 years remained almost constant and showed 9.24 +/- 0.34mg/dl (mean +/- SD, n = 242), 3.34 +/- 0.38mg/dl (n = 242), 0.870 +/- 0.121mg/dl (n = 242), 3.20 +/- 0.54mg/dl GF (n = 189) and 103 +/- 17ml/min (n = 137), respectively. All healthy volunteers (n = 326) had measurements of PTH in the blood. From 20 to 50 years, normal PTH mean was 374 +/- 97pg/ml (+/- SD, n = 237) and ranged from 180-568pg/ml, and from 60 to 80 years it was 471 +/- 133pg/ml (n = 34) and ranged from 205-737pg/ml. Since we found that PTH was markedly elevated above normal when Ccr was below 40ml/min, and PTH was very significantly correlated with the reciprocal of Ccr (r = 0.8996, P less than 0.001) using a multivariate analysis, all of the patients whose Ccr was higher than 40ml/min were selected and examined in the following studies. Serum PTH values completely separated patients with surgically proven primary hyperparathyroidism (1 degree HPT) from malignant associated hypercalcemia (MAH), and patients with idiopathic hypoparathyroidism (IHP) from pseudohypoparathyroidism (PHP), both of which were diagnosed by Ellsworth-Howard test. PTH values in all of the patients with 1 degree HPT (n = 23) were above normal, but those with MAH (n = 6) were below the normal or lower normal range. PTH values in patients with PHP (n = 7) showed above normal, while those with IHP (n = 5) were below the normal range. PTH was normalized in post operative status in all patients after parathyroidectomy (n = 6). These results indicate that this PTH RIA is extremely useful for the differential diagnosis in diseases with calcium abnormalities.
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PMID:[Clinical studies using a highly sensitive radioimmunoassay for mid-region and carboxy terminus of parathyroid hormone in normal, hypo- and hypercalcemic states]. 255 7

The pathogeneses of hypercalcemia and hypophosphatemia which developed in a patient with metastatic invasive ductal breast carcinoma were studied. The patient had low plasma levels of immunoreactive parathyroid hormone (PTH) and 1,25(OH)2D, increased nephrogenous cyclic adenosine monophosphate (cAMP) excretion and low TmPO4/GFR, suggesting the presence of humoral PTH-like activity. The tumor extract showed activities which would stimulate bone resorption in vitro and cAMP generation in the osteogenic cell line, MC3T3 E1, and in the rat kidney cortex. In addition, the extract stimulated epidermal growth factor (EGF)-independent colony formation of the NRK 49F cells in soft agar, and inhibited the binding of EGF to A431 cells, indicating it to have transforming growth factor (TGF)-alpha activity. The extract contained appreciable amounts of immunoreactive PTH-related protein (PTH-rP) but negligible amounts of immunoreactive PTH. Thus, the PTH-like activity for stimulating cAMP generation in the bone and kidney was attributed to PTH-rP. Chromatographic analyses on reverse phase high performance liquid chromatography (HPLC) separated the PTH-rP activity from that of TGF-alpha and the bone resorbing activity in vitro was found only in the fractions of PTH-rP. It was concluded that this breast cancer produced PTH-rP as well as TGF-alpha, and the former was thought to have a major role to play in the humoral hypercalcemia of malignancy observed in this patient.
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PMID:Parathyroid hormone-related protein and transforming growth factor activities in an extract from a breast cancer associated with humoral hypercalcemia of malignancy. 255 42

Carbetimer is a new antineoplastic agent whose limiting toxicity consists of dose- and treatment duration-dependent hypercalcemia. We examined the short-term effects of Carbetimer on calcium metabolism on days, 1, 3 and 5 during 11 5-day courses (6.5-8.2 g/m2/day given over daily 2-h infusions, q 3-4 weeks). Blood parameters were measured before and after Carbetimer, whereas urinary parameters were studied in three consecutive 2-h collections before, during and after Carbetimer infusions. Carbetimer effects were similar regardless of the infusion day. We found a consistent decrease of plasma ionized Ca (Ca2+) levels from 4.56 +/- 0.05 mg/dl before infusion to 4.28 +/- 0.06 mg/dl after infusion (P less than 0.001) whereas total serum Ca (corrected for protein levels) did not change. The fall of Ca2+ stimulated parathyroid function, as suggested by the increased plasma PTH levels, the decreased serum phosphorus and TmP/GFR index, or the increased urinary phosphate and cyclic AMP excretion. Carbetimer infusions also induced a marked increase in urinary Ca excretion (expressed as mg Ca/mg creatinine) from 0.093 +/- 0.011 before to 0.359 +/- 0.042 during and 0.177 +/- 0.031 after infusion (P less than 0.011). These changes were best explained by Carbetimer-induced Ca chelation that we confirmed in vitro by incubating Carbetimer at various concentrations in whole blood for 2 h at 37 degrees C, e.g. 2 mg of Carbetimer/ml lowered Ca2+ from 4.82 to 3.20 mg/dl without changing total Ca levels. On the other hand, a direct effect of Carbetimer on bone cannot be excluded since we observed an increase of serum osteocalcin levels from 2.0 +/- 0.3 to 2.5 +/- 0.4 ng/ml after infusion (P less than 0.001). In summary, the short-term effects of Carbetimer on calcium metabolism markedly differ from the long-term effects. They mainly consist of a dose-related calcium chelation leading to a decrease in Ca2+ levels, an increase in urinary Ca excretion and a stimulation of parathyroid function.
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PMID:Short-term effects of Carbetimer on calcium and bone metabolism in man. 263 64

The pathophysiological mechanisms of hypercalcaemia were assessed in 50 rehydrated patients with cancer-associated hypercalcaemia. Surprisingly, renal tubular calcium reabsorption appeared to increase progressively as serum calcium rose, suggesting that the nomogram used for the calculation may have been inaccurate, in absolute terms, probably due to its failure to take account of the levels of urinary sodium excretion. There were significant differences in the mechanisms of hypercalcaemia in different patient subgroups, however, independent of differences in urinary sodium excretion. In those with few or no bone metastases, increased renal tubular calcium reabsorption was the principal cause of hypercalcaemia, often in association with increased bone resorption. These abnormalities were thought to reflect the renal and skeletal actions of a tumour-associated humoral mediator. The main cause of hypercalcaemia in those with extensive metastatic bone disease was increased bone resorption, with contributions from impairment of glomerular filtration rate and, to a minor extent, increased renal tubular calcium reabsorption. These abnormalities were thought to reflect a mainly local-osteolytic mechanism of hypercalcaemia with secondary impairment of GFR. Of all the biochemical variables assessed pre-treatment, the renal tubular component of hypercalcaemia correlated most strongly with post-treatment serum calcium values (r = 0.61, P less than 0.001). Because of their generally lower levels of renal tubular calcium reabsorption, patients with extensive skeletal metastases also had significantly lower post treatment calcium values than patients with few or no metastases (P less than 0.05). These data indicate that the pathophysiological mechanisms of hypercalcaemia are a major determinant of the calcium lowering response after antihypercalcaemic treatment. This should be taken into account during comparative studies of antihypercalcaemic therapy in patients with malignancy.
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PMID:Malignancy-associated hypercalcaemia: relationship between mechanisms of hypercalcaemia and response to antihypercalcaemic therapy. 297 9

The relation between urinary sodium excretion (NaE) and renal tubular calcium reabsorption (TmCa/GFR) was assessed in patients with hypercalcaemia associated with malignancy and primary hyperparathyroidism. On acute saline loading of seven normally hydrated patients with primary hyperparathyroidism and five patients with malignancy, raised values of TmCa/GFR were reduced to normal in most cases, in association with increases in NaE. The reduction in TmCa/GFR, which occurred, may have been due to a reduction in proximal tubular calcium reabsorption associated with sodium: this would have obscured the effect of humorally mediated increases in distal tubular calcium reabsorption, which are stimulated either by parathyroid hormone or by a putative humoral mediator in hypercalcaemia of malignancy. In patients who were normally hydrated NaE and TmCa/GFR were not significantly correlated. When data were included from patients who were dehydrated and from those undergoing acute saline loading, significant inverse correlations between NaE and TmCa/GFR were observed both in primary hyperparathyroidism (r = -0.49; p less than 0.02) and malignancy (r = -0.60; p less than 0.001). In clinical practice changes in TmCa/GFR associated with sodium seem to be of minor importance under normal circumstances, but they become evident at the upper and lower extremes of urinary sodium excretion. In clinical studies of renal calcium handling urinary sodium excretion must also be assessed, as interpreting TmCa/GFR data is difficult in states of excessive sodium loading or depletion.
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PMID:Influence of urinary sodium excretion on the clinical assessment of renal tubular calcium reabsorption in hypercalcaemic man. 372 17

Twenty patients with malignant hypercalcemia were treated with aminohydroxypropylidene bisphosphonate (AHPrBP, previously APD) a potent inhibitor of osteoclast-mediated bone resorption. To assess the efficacy of oral vs intravenous therapy, the patients were divided into two groups: group A received AHPrBP intravenously (30 mg/day), and group B received the drug orally (1200 mg/day) for 6 days. In both groups all the patients responded to AHPrBP with a rapid decrease in plasma calcium concentration after a mean time lag of 1 day. Within 9 days plasma calcium concentration fell from 3.42 +/- 0.13 (mean +/- SEM) to 2.26 +/- 0.13 mmol/l in group A and from 3.28 +/- 0.12 to 2.24 +/- 0.09 mmol/l in group B. There was no significant difference in plasma Ca level between both groups on days 4, 6, and 9, and plasma Ca was within the normal range in all patients on day 9. On both treatment regimens urinary calcium excretion fell dramatically and similarly. Plasma phosphate concentration decreased significantly on AHPrBP in both groups of patients, reaching values slightly below the normal range from day 4 to day 9. TmP/GFR decreased progressively on AHPrBP. However, this decrement was significant at day 6 only. Plasma parathyroid hormone concentration rose significantly in both groups from day 4 to day 9. We conclude that at the doses used in the present study treatment of tumor-induced hypercalcemia with AHPrBP is equally effective whether given orally or intravenously.
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PMID:Oral versus intravenous AHPrBP (APD) in the treatment of hypercalcemia of malignancy. 376 3

TRCa calculations (using the values of plasma ultrafiltrable Ca and urinary Ca) revealed impaired renal Ca handling in 14/32 patients with transplanted kidneys. TRCa improved in relationship with the increment in renal transplant function, and was within the normal range in all patients with GFR above 50 ml/min. There was a positive correlation between serum Ca and TRCa; hypocalcaemia was found in 9 patients and hypercalcaemia in 3. In the majority of hypocalcaemic patients TRCa impairment was discovered, however, pathologically decreased serum Ca values were found in only one half of the patients with impaired TRCa. In most hypocalcaemic patients the concomitant renal transplant insufficiency, hyperphosphataemia and/or insufficient dietary Ca intake seemed likely to have contributed to serum Ca depletion.
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PMID:Transient impairment of tubular reabsorption of calcium (TRCa) after renal transplantation. 391 85

In 42 myeloma patients our results confirm the association of light chain proteinuria and renal damage, but suggest that while the amount of light chain excreted is an important factor, only some light chains are nephrotoxic. The excretion of the proximal tubular cell lysosomal enzyme N acetyl B D glucosaminidase was a sensitive index of tubular injury, while the presence of low molecular weight proteinuria (Retinol Binding Protein and Lysozyme) was shown to indicate tubular dysfunction in a kidney sufficiently damaged to produce an impaired GFR. Isolated defects of distal tubular function (acid load response and concentrating ability) were rare. Such changes were seen mainly as part of global renal impairment and were usually associated with such specific pathophysiological conditions as plasma hyperviscosity or tubular crystal deposition. Hypercalcemia had a specific effect on the concentrating ability independent of any impairment of renal acidification.
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PMID:Tubular function in multiple myeloma. 393 70

Ten hypercalcaemic members from three generations of a family with familial hypocalciuric hypercalcaemia (FHH) were compared with age and sex matched healthy subjects. Two of the former had undergone unsuccessful subtotal parathyroidectomy. Our results showed that the hypercalcaemia was mainly attributable to an increased capacity for tubular reabsorption of calcium, but in part also to an increased release of calcium from bone. The relative hypermagnesaemia had a similar dual origin. The serum phosphate concentration was low and this could be accounted for in full by a decrease in renal tubular reabsorption of phosphate, as assessed by the renal threshold phosphate concentration (TmPO4/GFR). The results of PHT measurements with two radioimmunoassays were equivocal. Most patients had normal serum PTH values, but with one assay mean serum PTH was significantly higher in the hypercalcaemic group. We conclude that the abnormalities of the divalent cation and phosphate metabolism cannot be accounted for in full by increased circulating PTH activity, and are predominantly due to an intrinsic renal abnormality.
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PMID:Familial hypocalciuric hypercalcaemia I: Renal handling of calcium, magnesium and phosphate. 397 25

A study of 28 consecutively admitted patients with active acromegaly revealed the following results with regards to calcium and phosphate metabolism. When compared with controls, there was an increase in serum calcium levels corrected for total protein, urinary calcium was increased, but the tubular re-absorption of calcium was normal. There was a negative correlation between the urinary cAMP and calcium excretion indicating that hyperabsorption of calcium from the gut is the cause of the increased urinary calcium excretion. Serum phosphate values were increased in acromegalics and correlated well with TmP/GFR which was also increased. Immunoreactive parathyroid hormone (PTH) was increased in 5 patients, three of whom had hypercalcaemia. In the remaining patients the PTH values were scattered within the normal range. The urinary cAMP/creatinine ratio was increased in acromegalics, but most of this difference was abolished when urinary cAMP was expressed relative to 100 ml of glomerulus filtrate. It is concluded that parathyroid hyperactivity is a feature of acromegaly.
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PMID:Calcium and phosphate metabolism in acromegaly. 625 98


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