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)

Multiple myeloma is a disseminated malignant neoplasm usually derived from a single clone of plasma cells. Patients with myeloma have diverse signs such as anemia, hypercalcemia, uremia, pathologic fractures, and recurrent infections. Extraosseous manifestations are found in less than 5% of patients with multiple myeloma. They can arise in any tissue, and their presence has been associated with more aggressive disease. The purpose of this essay is to illustrate the imaging findings of extraosseous myeloma and heighten awareness of this unusual manifestation of multiple myeloma.
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PMID:Extraosseous multiple myeloma: imaging features. 807 98

Supplementation of cyanate in rats caused a significant decrease in serum GSH and increase in calcium and phosphate level both in serum and lens. Consequently, these changes led to induce acidosis uremia in serum and hypercalcemia and hyperphosphatemia in lens which may be possible causing factor for cataract.
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PMID:In vivo effect of cyanate on serum and eye lens in rat. 850 Aug 20

The use of 1 alpha-hydroxyvitamin D3 [1 alpha(OH)D3] derivatives in a uremic patient is justified only in the treatment of hyperparathyroidism (i.e. when plasma intact parathyroid hormone - PTH - levels are above five or three times the upper limit of normal according to whether the patient is on continuous ambulatory peritoneal dialysis or on hemodialysis and between 0.5-1.5, 1-2 and 2-3 times the upper limit of normal for a creatinine clearance of, respectively, 30, between 30 and 10, or below 10 ml/min/1.73 m2). The following prerequisites have however to be satisfied: (1) a good vitamin D3 repletion should be secured by plasma 25(OH(D) levels of 20-30 ng/ml (if necessary by administration of native vitamin D or 25(OH)D3), and (2) phosphate retention (which is aggravated by the increased phosphate intestinal absorption induced by the 1 alpha (OH)D derivatives) and the consequent possible hyperphosphatemia should be prevented or corrected by the oral administration of alkaline salts of calcium given before the meals as phosphate binders without inducing hypercalcemia. These prerequisites explain the narrow therapeutical margin of 1 alpha (OH)D3 derivatives in uremic patients before dialysis (more so in the adult than in the child) and the possible broadening of this margin in the patients on dialysis by the use of low dialysate calcium concentrations (1.25-1.00 mmol/l) in order to prevent hypercalcemia by inducing a negative perdialytic calcium balance. Once hyperphosphatemia is prevented by oral calcium, 1 alpha (OH)D3 derivatives have the advantage to suppress the transcription of the prepro PTH gene by a mechanism independent of an increase in plasma calcium. Controlled randomized trials have not confirmed the claimed advantage in efficacy and safety of the parenteral versus the oral route nor of the intermittent versus the daily mode of their administration. The advantages of using the so called 'nonhypercalcemic hyperphosphatemic' vitamin D3 derivatives in combination with oral calcium over 1 alpha(OH)D3 derivatives in the treatment of uremic hyperparathyroidism are still waiting for clinical demonstration. Vitamin D derivatives have no place in the treatment of aluminic bone diseases which necessitate long term deferoxamine treatment and prevention of aluminum exposure by the dialysate and the phosphate binders. They are not indicated in the treatment of 'idiopathic' adynamic bone disease which is due to uremia per se combined with an excessive PTH suppression for the degree of renal failure. This low bone turnover pattern is associated with an increased risk of hypercalcemia and hyperphosphatemia and necessitates only a stimulation of PTH secretion by inducing a negative calcium balance with a lower dialysate calcium concentration or simply by discontinuing the oral calcium supplement in the uremic patient not yet dialyzed. In rare cases this pattern is due to a granulomatosis and is corrected by prednisone.
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PMID:1-alpha-Hydroxyvitamin D3 derivatives in the treatment of renal bone diseases: justification and optimal modalities of administration. 856 75

We have previously reported that 19-nor-1,25-(OH)2D2, a new analog of 1,25-(OH)2D3, suppresses parathyroid hormone (PTH) secretion in uremic rats in the absence of hypercalcemia or hyperphosphatemia. In the current study, we examined the effect of 19-nor-1,25-(OH)2D2 on parathyroid gland growth and intestinal vitamin D receptor (VDR) content. After induction of uremia by 5/6 nephrectomy, rats were divided into five experimental groups and received intraperitoneal injections of vehicle, 1,25-(OH)2D3 (2 or 6 ng/rat), or 19-nor-1,25-(OH)2D2 (25 or 100 ng/rat) three times a week for 8 weeks. Twelve normal rats received vehicle and served as the normal control group. During the course of the study, rats were maintained on a 1.0% calcium and 0.8% phosphorus diet. The higher dose of 1,25-(OH)2D3, 6 ng, significantly decreased PTH from 52.7 +/- 10.2 pg/mL in the uremic control group to 25.7 +/- 6.7 pg/mL (P < 0.01). This dose of 1,25-(OH)2D3, however, increased serum levels of both ionized calcium (4.71 +/- 0.05 to 4.85 +/- 0.06 mg/dL; P < 0.05) and phosphorus (4.34 +/- 0.30 to 6.67 +/- 0.63 mg/dL; P < 0.01). Both doses of 19-nor-1,25-(OH)2D2 decreased serum PTH as effectively as 1,25-(OH)2D3 without changes in serum calcium or phosphorus. The 100-ng dose of 19-nor-1,25-(OH)2D2 decreased PTH to 20.7 +/- 3.1 pg/mL (P < 0.01) and suppressed parathyroid gland growth by more than 50%. Both doses of 19-nor-1,25-(OH)2D2 also decreased endogenous 1,25-(OH)2D3 levels compared with uremic control rats (25 ng:30.4 +/- 2.0, P < 0.05, and 100 ng:27.9 +/- 3.2, P < 0.01, v 48.4 +/- 6.6 pg/mL). The 6-ng dose of 1,25-(OH)2D3 elevated intestinal VDR content (138.5 +/- 20.0 fmol/mg protein) compared with animals receiving both doses of 19-nor-1,25-(OH)2D2 (25 ng:84.0 +/- 11.9, P < 0.05, and 100 ng:78.4 +/- 10.9, P < 0.01). This was probably attributable to the marked decrease in endogenous 1,25-(OH)2D3 levels caused by both doses of 19-nor-1,25-(OH)2D2 because intestinal VDR correlated directly with serum 1,25-(OH)2D3 (r = 0.963; P = 0.008). Thus, 19-nor-1,25-(OH)2D2 appears to exert a selective action on the parathyroid glands compared with the intestine. Its low calcemic and phosphatemic properties may result from the decreased endogenous 1,25-(OH)2D3 levels that lead to a reduction in intestinal VDR. This selectivity makes this analog ideal for the treatment of secondary hyperparathyroidism.
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PMID:A new analog of 1,25-(OH)2D3, 19-NOR-1,25-(OH)2D2, suppresses serum PTH and parathyroid gland growth in uremic rats without elevation of intestinal vitamin D receptor content. 921 8

There are many pathological causes and potential mechanisms for hypercalcemia. We measured intact parathyroid hormone (PTH) and parathyroid hormone related protein (PTHrP) in the hypercalcemic in-patients and attempted to evaluate the roles of PTH and PTHrP in hypercalcemia due to malignancy. We performed a prospective study of 178 patients with corrected serum calcium concentrations greater than 2.74 mmol/l in a hospital over a 3-year period. We measured calcium and albumin using a Hitachi 747 autoanalyzer, and we measured PTH and PTHrP by two-site immunoradiometric assays (IRMA). Hypercalcemia was attributed to malignancy alone in 93 patients (52.3%), primary hyperparathyroidism (HPT) alone in 28 patients (15.7%), uremia with hemodialysis in 23 patients (12.9%), unknown in 16 patients (9%), primary HPT coexisting with malignancy in 7 patients (3.9%) and other rare causes (6.2%). Plasma PTHrP levels were elevated in 71/93 (76.3%) patients with hypercalcemia due to malignancy, but the elevated PTHrP percentage differed for each kind of tumor. PTHrP levels were elevated in 100% of patients with squamous carcinomas (CA) in the lung, esophagus, skin, cholangiocarcinoma of liver, and breast CA. The positive bony metastatic rate was 44.1% (41/93). There was no correlation between high PTHrP and bony metastasis. There was a good correlation between the corrected serum calcium and PTHrP levels (r = 0.476, p < 0.001), but no correlation between survival time and serum calcium level or PTHrP level. There was no significant difference in life expectancy after cancer diagnosis between the high PTHrP group and normal PTHrP group, and there was no significant difference in life expectancy after the first occurrence of hypercalcemia between the two groups. Measurement of both PTH and PTHrP levels led to a change in the initial diagnosis in 7 patients. In routine practice, measurement of serum PTH alone is not enough. This study suggests that the appropriate combination of PTH and PTHrP assays results in a more accurate diagnosis of the hypercalcemic causes. In addition, especially high PTHrP levels should be screened for malignancy. However, the prognosis in cancer patients after hypercalcemia with high PTHrP group, as compared to those with the normal PTHrP group is not significantly different.
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PMID:Parathyroid hormone and parathyroid hormone related protein assays in the investigation of hypercalcemic patients in hospital in a Chinese population. 930 39

Chronic uremia is associated with secondary hyperparathyroidism (HPT). The purpose of the present investigation was to study the reversibility of secondary HPT after reversal of uremia by an isogenic kidney transplantation in the rat. Secondary HPT was induced in two models: Model A comprised 5/6 nephrectomized rats kept on a standard diet (N = 12; PTH 210 +/- 43 pg/ml; plasma urea 24 +/- 2 mmol/liter; and normal control rats, N = 12; PTH 45 +/- 5 pg/ml; plasma urea 6 +/- 0.2 mmol/liter); and Model B comprised 5/6 nephrectomized rats kept on a high phosphorus diet (N = 12; PTH 769 +/- 157 pg/ml; plasma urea 18 +/- 2 mmol/liter). The parathyroid function was examined by measuring the secretory response of PTH to an acute induction of hypo- and hypercalcemia. Acute hypocalcemia in the hyperphosphatemic uremic rats did not significantly increase serum PTH levels (N = 6, delta Ca2+ -0.56 mmol/liter; maximal PTH 1045 +/- 164 pg/ml; basal PTH 690 +/- 134 pg/ml; NS). During hypercalcemia the PTH levels were significantly higher than in the normal controls (N = 6; minimal PTH 24 +/- 5 pg/ml vs. normal controls 5 +/- 0.2 pg/ml, P < 0.05). After 20 weeks of uremia, the uremia was reversed by the isogenic kidney transplantation. One week after reversal of the uremia the PTH levels became normal in both models A and B (28 +/- 6 and 63 +/- 16 pg/ml, respectively) and the kidney transplanted rats from model B had a normal secretory response of PTH to both hypo- and hypercalcemia. To study whether both parathyroid cell hypertrophy and hyperplasia could be down-regulated, 8 uremic glands (N = 9) or 20 normal glands (N = 6) were implanted into one normal rat. Within two weeks the rats regained normocalcemia and PTH levels remained normal from the third day after the increase of glandular mass. The 20 gland rats all had normal PTH suppressibility in response to calcium (minimal PTH 5 +/- 0.3 pg/ml). In conclusion, experimental severe secondary hyperparathyroidism is reversible very quickly after the reversal of uremia. Hyperphosphatemia in uremia is important for the non-suppressibility of the parathyroid glands to calcium. In non-uremic rats even severe parathyroid hyperplasia can be controlled, resulting in normal plasma PTH and Ca2+ levels and in a normal response to hypercalcemia. Thus, the minimal PTH secretion obtained during the induction of hypercalcemia is not an expression of the parathyroid mass.
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PMID:Reversibility of experimental secondary hyperparathyroidism. 935 Jun 46

The lethality of the endocrine tumors associated with multiple endocrine neoplasia type I (MEN-I), particularly the pancreatic islet cell tumors, has been controversial. We evaluated the cause and age of death in MEN-I kindreds. Our database contains 34 distinct kindreds with 1838 members. Reliable death data are available for 103 people (excluding accidents and age < 18 years). We compared survival curves of MEN-I patients who died from causes related to MEN-I with those from MEN-I carriers who died from a nonendocrine cause and unaffected kindred members. We also compared ages of death between affected and unaffected members of MEN-I kindreds. Of 59 MEN-I-affected patients, 27 died directly of MEN-I-specific illness and 32 of non-MEN-I causes. The MEN-I-specific deaths occurred at a younger age (median 47 years) than either MEN-I patients whose death was from some nonendocrine cause (median 60 years, p < 0.02) or than all kindred members who did not die of MEN-I disease (median 55 years, p < 0.05). The causes of death of the MEN-I patients included islet cell tumor (n = 12), ulcer disease (n = 6), hypercalcemia/uremia (n = 3), carcinoid tumor (n = 6), and nonendocrine malignancies (n = 9). There was no difference in survival between MEN-I carriers and unaffected kindred members. Of our MEN-I patients, 46% died from causes related to their endocrine tumors after a median age of 47 years, which was younger than family members who did not die from these tumors. Pancreatic islet cell tumors were the most common cause of death of MEN-I patients. Management of kindreds with MEN-I should include an aggressive screening program with early therapeutic intervention when a tumor is identified.
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PMID:Lethality of multiple endocrine neoplasia type I. 959 32

Cardiovascular diseases represent the major cause of death in hemodialysis patients. However, little information is available about the repercussion of uremia on cardiac valves. We retrospectively investigated the incidence rate of aortic stenosis (AS), from 1991 to 1996, in 110 hemodialysis patients followed by Doppler-echocardiography. Progressive AS was diagnosed in 16 patients who had a decrease in their indexed aortic valve area from 1.24 +/- 0.09 to 0.66 +/- 0.21 cm2/m2 of BSA in 16.8 +/- 1.9 months. The mean incidence of AS per year was of 3.3%, ranging from 1.5 to 8.0%. Eight patients died in less than 3 years after the diagnosis of AS with a mean survival time of 23.0 +/- 9.5 months. Survival curves using Kaplan-Meier estimates showed a statistically significant decrease in the survival rate of patients with AS compared with patients without valvulopathy (p < 0.001). They were older than patients with normal valve, 68.6 +/- 11.1 versus 56.7 +/- 16.0 years, respectively. Men were 4 times more affected than women and showed a significantly more rapid progression to AS than women. The calcium-phosphorus product was higher in AS patients, 5.43 +/- 0.98 than in patients without AS, 3.95 +/- 0.50 mM. It was mainly due to hyperphosphatemia without hypercalcemia and the hyperphosphatemia was associated with biological signs of hypoparathyroidism or adynamic bone disease in 62% of the cases. Plasma vitamin D3 was also higher in patients with AS, 20.5 +/- 13.5 ng/ml than in those with normal valves, 9.6 +/- 6.3 ng/ml. Logistic regression showed that age, vitamin D3 and hyperphosphatemia correctly predicted 56% of the AS cases. In conclusion, AS is frequent and of poor outcome in hemodialysis patients. Age, relatively high plasma vitamin D3 levels, and hyperphosphatemia, mostly due to hypoparathyroidism, must be considered as risk factors.
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PMID:Evolutive aortic stenosis in hemodialysis patients: analysis of risk factors. 1048 Jan 55

Vitamin D therapy is widely used for the treatment of secondary hyperparathyroidism associated with chronic renal failure. However, administration of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] or its precursor 1alpha(OH)D(3), especially in combination with calcium-based phosphate binders, often produces hypercalcemia. Several vitamin D analogs have been developed that retain the direct suppressive action of 1,25(OH)(2)D(3) on the parathyroid glands but have less calcemic activity. These analogs offer a safer and more effective means of controlling secondary hyperparathyroidism. 22-Oxa-1,25(OH)(2)D(3) (22-oxacalcitriol or OCT), 19-nor-1, 25(OH)(2)D(2) (19-norD(2)) and 1alpha(OH)D(2) have been tested in animal models of uremia and in clinical trials. Intravenous 19-norD(2) and oral 1alpha(OH)D(2) have been approved for use in the United States; OCT is currently under review. The mechanisms by which these analogs exert their selective actions on the parathyroid glands are under investigation. The low calcemic activity of OCT has been attributed to its rapid clearance which prevents sustained effects on intestinal calcium absorption and bone resorption, but still allows a prolonged suppression of PTH gene expression. The selectivity of 19-norD(2) and 1alpha(OH)D(2) is achieved by a distinct mechanism(s). Knowledge of how these compounds exert their selective actions on the parathyroid glands may allow the design of more effective analogs in the future.
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PMID:Vitamin D analogs: perspectives for treatment. 1068 62

Due to urea's role in producing concentrated urine, its transport is critically important to the conservation of body water. Within the renal inner medulla, urea is transported by both facilitated and active urea transport mechanisms. The vasopressin-regulated, facilitated urea transporter (UT-A1) in the terminal inner medullary collecting duct (IMCD) permits high rates of transepithelial urea transport and results in delivery of large quantities of urea into the deepest portions of the inner medulla where it is needed to maintain a high interstitial osmolality for maximal urine concentration. Four cDNA isoforms of the UT-A urea transporter family have been cloned. In addition, there are three secondary active, sodium-dependent, urea transport mechanisms in IMCD subsegments: (1) active urea secretion in the apical membrane of the terminal IMCD from untreated rats; (2) active urea absorption in the apical membrane of the initial IMCD from low-protein fed or hypercalcemic rats; and (3) active urea absorption in the basolateral membrane of the initial IMCD from furosemide-treated rats. This review will focus on integrative studies of the rapid and long-term regulation of urea transporters in rats with reduced urine concentrating ability. These studies led to the surprising result that the basal-facilitated urea permeability in the terminal IMCD and UT-A1 protein abundance are increased during in vivo conditions associated with an impaired urine concentrating ability. In contrast, there are two response patterns of active urea transporters: (1) hypercalcemia, a low-protein diet, and furosemide result in induction of active urea absorption in the initial IMCD, albeit by different mechanisms, and inhibition of active urea secretion in the terminal IMCD; while (2) water diuresis results in up-regulation of active urea secretion in the terminal IMCD without any active urea absorption in the initial IMCD. The first pattern contributes to the urine concentrating defect by increasing urea delivery to the base of the inner medulla, thus decreasing urea delivery distally to the inner medullary tip. The second response pattern will directly decrease urea content in the deep inner medulla. UT-A urea transporters are also expressed outside the kidney. Recent studies show that the liver has phloretin-inhibitable urea transport and that it occurs via a 49 kDa UT-A protein. When rats are made uremic, the abundance of this 49 kDa UT-A protein increases in the liver in vivo. This up-regulation of the 49 kDa UT-A protein may allow hepatocytes to increase ureagenesis to reduce the accumulation of ammonium and/or bicarbonate in uremia.
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PMID:Regulation of urea transporter proteins in kidney and liver. 1074 66

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