UMLS:C0020437 - FACTA Search

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Query: UMLS:C0020437 (hypercalcemia)
10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Parathyroid hormone-related protein (PTHrP) was measured in plasma by a new immunoradiometric assay (IRMA) from Nichols Institute. The assay is specific for PTHrP and shows excellent parallelism when measuring keratinocyte fluid, samples with high PTHrP content, and PTHrP-supplemented plasma. A precision profile established the assay detection limit at 0.7 pmol/L. PTHrP was unstable in plasma, but the degradation rate was patient-specific. Because delay in separation resulted in loss of PTHrP immunoreactivity, samples were collected into tubes containing protease inhibitors (aprotinin, leupeptin, pepstatin, and EDTA) and separated within 30 min. Among normal subjects, 78% had PTHrP values greater than the detection limit; the reference range established was < 0.7-2.6 pmol/L. Of patients with hypercalcemia associated with malignancy, 46% had PTHrP > 2.6 pmol/L. PTHrP was increased in patients with breast (73%), genitourinary (64%), or lung (46%) malignancy but was rarely above normal in patients with hematological (29%) or gastrointestinal (33%) malignancy. PTHrP and nephrogenous cyclic adenosine monophosphate (NcAMP) were strongly correlated (r = 0.63, P < 0.01) in 37 patients with PTHrP values greater than the detection limit, but 8 patients had PTHrP and parathyroid hormone [PTH(1-84)] values below the limit of detection with inappropriate or increased NcAMP. Five of these eight patients had small cell carcinoma of lung. These patients may have secreted a factor that is not detected by the IRMAs of PTHrP or PTH used in this study but that produces hypercalcemia by means of cAMP-mediated mechanisms.
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PMID:Clinical and laboratory studies of a new immunoradiometric assay of parathyroid hormone-related protein. 844 50

Increased calcitonin (CT) levels have been reported in chronic renal failure, even before the uraemic phase and in the absence of hypercalcaemia. Furthermore, a sigmoidal CT-calcium relationship was recently observed in rats and haemodialysed patients. We carried out the present investigation in order to assess: (a) whether the sigmoidal CT-calcium relationship is also evident in renal patients with a variable degree of renal failure and in normal subjects; (b) whether the four secretory parameters already described for the PTH-calcium relation curve might be described for CT too; (c) whether any change in some, if any, of these secretory parameters could be found at a variable degree of renal insufficiency. We studied 33 renal patients (RP), with a variable degree of renal failure (creatinine clearance ranging from 16 to 164 ml/min), and 10 normal subjects (C). All RP and C were submitted to a basal evaluation including the assessment of (1) basal concentrations of 1,25(OH)2 vitamin D, 25(OH) vitamin D, monomeric CT, intact PTH; (2) GFR by Cr51EDTA clearance. On the 2 subsequent days, a hypocalcaemic test (Na2-EDTA about 37 mg/kg of body-weight/2 h) and a hypercalcaemic test (Ca gluconate giving 8 mg/kg body-weight/2 h of Ca element) were carried out for the assessment of both CT and PTH secretory parameters. According to GFR values, the RP were divided into three groups: group RP1 (GFR > 70 ml/min per 1.73 m2; n = 10), group RP2 (GFR between 30 and 70 ml/min per 1.73 m2; n = 15), group RP3 (GFR < 30 ml/min per 1.73 m2; n = 8). In most, but not all, RP and C a sigmoidal CT-calcium relationship was evident, opposite in direction to the PTH-calcium relation curve. In these RP and C the four secretory parameters, characteristic for the PTH-calcium secretion curve, were calculated for CT too. When pooled RP and C were considered, both minimal (9.0 +/- 6.4 pg/ml) and maximal CT levels (71.8 +/- 56.2 pg/ml) significantly differed from basal levels (24.3 +/- 18 pg/ml; P < 0.001). The CT set point (CT SP) and sensitivity (CT SENS) values were significantly higher and lower than the corresponding PTH secretory parameters (CT SP 1.39 +/- 0.08 mmol/l, PTH SP 1.23 +/- 0.05 mmol/l, P < 0.001) (CT SENS 243 +/- 67%/mmol, PTH SENS 598 +/- 329%, P < 0.001). However, the CT SP values were strictly correlated with PTH SP values (r = 0.78, P < 0.001). When CT secretory parameters were considered separately in the RP groups, increased levels of basal (36.1 +/- 28.6 pg/ml), minimal (17.9 +/- 10.4), and maximal (139.9 +/- 39.7) CT levels were found in the RP3 group, when compared with both the other RP groups and C. No significant difference was found as regards the CT SP and CT SENS values between RP and CT. These results suggest that (1) CT secretion is homeostatically controlled by calcium changes in the same range of the PTH-calcium system; (2) a sigmoidal CT-calcium relationship is demonstrable in most (but not all) RP and C; in these subjects it is possible to calculate the CT secretory parameters as for PTH; (3) the increase in CT levels in the course of chronic renal failure is quite similar to the already known increase of PTH, and is characterized by the increase of basal, minimal and maximal CT values, suggesting that an increased secretion of CT by the thyroid C-cells (rather than CT retention due to a decrease in renal function), is responsible for these findings.
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PMID:The calcitonin-calcium relation curve and calcitonin secretory parameters in renal patients with variable degrees of renal function. 880 22

The relationship between PTH and calcium is best represented as a sigmoidal curve. In the normal animal and human, basal PTH is positioned at approximately 25% of maximal PTH and responds rapidly to small changes in calcium in either direction. Since PTH secretion is designed to respond to either hypo- or hypercalcemia, the study was performed to evaluate whether the parathyroid gland would respond differently to hypocalcemia when the reduction in serum calcium was initiated from sustained hypercalcemia with maximal PTH suppression. Nine dogs were studied and the experimental protocol consisted of two separate parts in which the same dogs were used and the order of study was randomly assigned. For the hypercalcemic part, calcium chloride was infused intravenously to increase serum calcium to between 1.60 and 1.70 mM at 30 minutes and then continued for another 90 minutes to clamp the serum calcium at this level. Sodium EDTA was then infused to lower the serum calcium at a constant rate to less than 0.85 mM. For the normocalcemic part, 5% dextrose in water was infused for two hours to control for fluid volume and time, and then EDTA was infused to lower the serum calcium at a constant rate to less than 0.85 mM. The results show that for the same serum calcium concentration at every 0.05 mM decrement in serum calcium below normal, PTH was less in the hypercalcemic than the normocalcemic dogs (P < 0.02). During the induction of hypocalcemia in the normocalcemic dogs, a characteristic sigmoidal curve was observed in which a small decrease in the serum calcium induced a brisk increase in PTH and a maximal PTH level was rapidly attained; however, during the induction of hypocalcemia in the hypercalcemic dogs, the increase in PTH was progressive, but linear and it was not certain that a maximal PTH level was attained. In conclusion, a sustained period of hypercalcemia resulted in a decreased PTH response to hypocalcemia and reduced the efficiency of the sigmoidal PTH-calcium relationship. Whether the mechanism for this difference in PTH secretion is due to secretory products, modification of the calcium receptor, or changes in intercellular communication among parathyroid cells deserves further study.
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PMID:A reduced PTH response to hypocalcemia after a short period of hypercalcemia: a study in dogs. 894 17

The objective of this study was to evaluate the involvement of the pineal gland in modulation of parathyroid hormone (PTH) and calcitonin release found in rats after changes in activity of cervical sympathetic nerves. The response of serum PTH to a hypocalcemia produced by EDTA injection, and of serum calcitonin to a hypercalcemia produced by administering calcium chloride, were studied in rats at the time of the wallerian degeneration of regional sympathetic nerves (i.e., 16 hr after superior cervical ganglionectomy, SCGx). Rats received a pinealectomy or its sham-operation 4 days before SCGx. During wallerian degeneration of nerves after SCGx, a higher hypocalcemia and a lower PTH response were found as compared to sham-SCGx rats, regardless of whether the pineal gland was present or not. When the response of calcitonin to a bolus injection of calcium chloride was assessed, rats subjected to SCGx 16 hr earlier showed a depressed calcitonin release, which was also unaffected after pinealectomy. To a similar extent in pinealectomized and sham-pinealectomized rats, a mild stress given by the subcutaneous injection of turpentine oil brought about a greater hypocalcemia after EDTA, concomitantly with a higher PTH secretory response. In turpentine oil-injected rats, the rise of serum calcitonin was significantly greater than that of vehicle-treated rats, regardless of pineal presence. The results further indicate that cervical autonomic nerves constitute a pathway through which the brain modulates calcium homeostasis and do not support the participation of the pineal gland in short term changes of PTH or calcitonin release.
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PMID:The influence of cervical sympathetic neurons on parathyroid hormone and calcitonin release in the rat: independence of pineal mediation. 906 64

Osteoporosis is a common manifestation of Cushing's syndrome, but the mechanisms responsible for this abnormality have not been defined. With the objective of analyzing parathyroid hormone (PTH) secretion in chronic hypercortisolism (CH), we evaluated 11 healthy subjects and 8 patients with CH, 6 with Cushing's disease and 2 with adrenal adenoma. These volunteers were submitted to tests of PTH stimulation through hypocalcemia (EDTA), PTH suppression through hypercalcemia (iv and oral calcium), and evaluation of bone mineral density (BMD) by DEXA. During the test of PTH stimulation, the calcium and magnesium concentrations of the normal and CH groups were similar. Patients with CH showed an increased PTH response to the hypocalcemic stimulus compared to controls. PTH values were significantly higher in the CH group at 70 (17.5 +/- 3.5 vs 10.2 +/- 1.3 pmol/l, P = 0.04), and 120 min (26.1 +/- 5.9 vs 11.3 +/- 1.9 pmol/l, P = 0.008) of EDTA infusion. The area under the curve for PTH during EDTA infusion was also significantly higher in patients with CH than in normal subjects (1867 +/- 453 and 805 +/- 148 pmol l(-1) 2 h(-1), P = 0.02). During the test of PTH suppression, calcium, magnesium and PTH levels of the patients with hypercortisolism and controls were similar. BMD was decreased in patients with hypercortisolism in the spine (0.977 +/- 0.052 vs 1.205 +/- 0.038 g/cm2 in controls, P<0.01). In conclusion, our results show that subjects with CH present decreased bone mass mainly in trabecular bone. The use of dynamic tests permitted the detection of increased PTH secretion in response to a hypocalcemic stimulus in CH patients that may probably be involved in the occurrence of osteoporosis in this state.
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PMID:Parathyroid hormone secretion in chronic human endogenous hypercortisolism. 1184 27

Abnormalities in calcium (Ca(2+)) homeostasis are reported in horses with several pathological conditions; however, there is little information on Ca(2+) regulation in horses. The objectives of the present study were to determine the Ca(2+) set-point in healthy horses, to determine whether the Ca(2+)/parathyroid hormone (PTH) response curves were characterized by hysteresis, and to determine if the order of experimentally induced hypocalcemia or hypercalcemia had an effect on PTH secretion. The Ca(2+) set-point and hysteresis were determined in 12 healthy horses by infusing Na(2)EDTA and calcium gluconate. The Ca(2+) set-point was 1.37 +/- 0.05 mmol/L, which is higher than values reported for humans and dogs (1.0-1.2 mmol/L). Hysteresis was present during hypocalcemia and hypercalcemia. Horses in which hypocalcemia was followed by hypercalcemia secreted more PTH (7440 +/- 740 pmol min/L) than horses in which hypercalcemia was followed by hypocalcemia (5990 +/- 570 pmol min/L). This study has demonstrated that the Ca(2+) set-point in the horse is higher than in other domestic animals and man. We have shown that the Ca(2+)/PTH relationship in horses is sigmoidal and displays hysteresis during both hypocalcemia and hypercalcemia, and that extracellular Ca(2+) concentrations may affect the response of the parathyroid gland to hypocalcemia.
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PMID:Hysteresis and calcium set-point for the calcium parathyroid hormone relationship in healthy horses. 1260 70

A case of severe hypercalcemia secondary to carcinoma of the lung is described in which hypokalemic alkalosis, renal failure and pancreatitis were also present. The relative importance of the few bone metastases found at autopsy is considered, and a probable endocrine-like effect of the tumour in the development of the hypercalcemia is postulated. Treatment of the hypercalcemia included administration of corticosteroids and disodium EDTA, peritoneal dialysis and subtotal parathyroidectomy; the most effective of these was peritoneal dialysis. Subtotal parathyroidectomy failed to produce a further decrease in serum calcium values. The occurrence of hypokalemic alkalosis in the presence of increased adrenocortical function and its relationship to the carcinoma of the lung are discussed. The possibility that this neoplasm produced two factors which caused systemic effects ordinarily associated with the function of endocrine glands must be considered.
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PMID:CARCINOMA OF LUNG WITH ADRENAL HYPERFUNCTION AND HYPERCALCEMIA TREATED BY PARATHYROIDECTOMY. 1424 67

Recently, we showed that both acute metabolic acidosis and respiratory acidosis stimulate parathyroid hormone (PTH) secretion in the dog. To evaluate the specific effect of acidosis, ionized calcium (iCa) was clamped at a normal value. Because iCa values normally increase during acute acidosis, we now have studied the PTH response to acute metabolic and respiratory acidosis in dogs in which the iCa concentration was allowed to increase (nonclamped) compared with dogs with a normal iCa concentration (clamped). Five groups of dogs were studied: control, metabolic (clamped and nonclamped), and respiratory (clamped and nonclamped) acidosis. Metabolic (HCl infusion) and respiratory (hypoventilation) acidosis was progressively induced during 60 min. In the two clamped groups, iCa was maintained at a normal value with an EDTA infusion. Both metabolic and respiratory acidosis increased (P < 0.05) iCa values in nonclamped groups. In metabolic acidosis, the increase in iCa was progressive and greater (P < 0.05) than in respiratory acidosis, in which iCa increased by 0.04 mM and then remained constant despite further pH reductions. The increase in PTH values was greater (P < 0.05) in clamped than in nonclamped groups (metabolic and respiratory acidosis). In the nonclamped metabolic acidosis group, PTH values first increased and then decreased from peak values when iCa increased by > 0.1 mM. In the nonclamped respiratory acidosis group, PTH values exceeded (P < 0.05) baseline values only after iCa values stopped increasing at a pH of 7.30. For the same increase in iCa in the nonclamped groups, PTH values increased more in metabolic acidosis. In conclusion, 1) both metabolic acidosis and respiratory acidosis stimulate PTH secretion; 2) the physiological increase in the iCa concentration during the induction of metabolic and respiratory acidosis reduces the magnitude of the PTH increase; 3) in metabolic acidosis, the increase in the iCa concentration can be of sufficient magnitude to reverse the increase in PTH values; and 4) for the same degree of acidosis-induced hypercalcemia, the increase in PTH values is greater in metabolic than in respiratory acidosis.
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PMID:Role of acidosis-induced increases in calcium on PTH secretion in acute metabolic and respiratory acidosis in the dog. 1472 29

We tested a new chemiluminescence immunoassay for intact parathyroid hormone (PTH) (ADVIA Centaur intact PTH-serum assay). It is a two-site sandwich immunoassay using direct chemiluminescence technology. We investigated precision with serum pools at three levels of the analyte, analyzed in duplicate for 12 days. Total coefficients of variation (CVs) were between 4.6 and 14.4%. The intra-assay precision was between 4.4 and 6.1%. Day-to-day reproducibility was between 1.5 and 13.1% for pools with a PTH concentration between 10 pg/ml and 70 pg/ml (about 1 to 7 pmol/l). The analytical sensitivity was 3.1 pg/ml. The functional sensitivity did not differ from 3 SD minimal detectable concentration (MDC). The linearity was good in the range from 3.1-1930 pg/ml. Comparison with the IRMA used in our laboratory was analyzed by Passing-Bablok and Bland-Altman plots and revealed a proportional bias of +/-60% (slope: 1.58; IC: 1.53 to 1.63) and a systematic bias of -3.3 pg/ml which should not have any clinical consequence in the interpretation of the results. We established a reference range based on our hospital population. We evaluated 87 subjects without abnormality of calcium metabolism and with normal vitamin D supply. Three groups of patients were also analyzed: 57 patients with vitamin D insufficiency, 17 with renal failure and 15 with hypercalcemia (7 due to primary hyperparathyroidism and 8 due to another etiology). Reference ranges were from 10.2 to 93 pg/ml for CLIA measurement and from 6.4 to 68 pg/ml for IRMA measurement. PTH values measured by CLIA varied from 6 to 142 pg/ml in patients with vitamin D insufficiency. By CLIA measurement, intact PTH was between 26 and 892 pg/ml in renal failure, between 54 and 201 pg/ml in primary hyperparathyroidism and between 0 and 29 pg/ml in patients with another etiology of hypercalcemia. The results of PTH measurements in EDTA plasma did not differ significantly from those performed in serum (Passing Bablock).
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PMID:Evaluation of a chemiluminescence immunoassay for the determination of intact parathyroid hormone using the ADVIA Centaur. 1557 12

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