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

Gallium nitrate was recently found to be effective treatment for resistant cancer-related hypercalcemia. In vitro and in vivo experiments have suggested that the drug directly inhibits calcium resorption from bone; however, the overall effects of gallium nitrate on calcium balance were unknown. We have completed metabolic balance studies in four patients who received this drug by prolonged infusion. All patients were in positive calcium balance while receiving the drug. Each patient also showed a substantial decrease in urinary calcium excretion. Serum phosphorus decreased in all four patients. There was no change in phosphorus, sodium, chloride, or magnesium balance or in creatinine clearance. We conclude that prolonged infusions of gallium nitrate reduce urinary calcium excretion and that the hypocalcemic effect of this drug is primarily due to inhibition of calcium resorption from bone. Thus, the drug may prove useful in reducing accelerated bone resorption in patients with bone metastases or chronic cancer-related hypercalcemia.
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PMID:Metabolic effects of gallium nitrate administered by prolonged infusion. 401 69

Increased tubular reabsorption of calcium is one of the three variables which can contribute to the pathogenesis of hypercalcaemia. It is therefore important to establish the normal range for this variable in a manner which allows for its variation with the plasma calcium concentration. Graphic methods depicting the relationship between urinary calcium excretion and plasma calcium concentration are valid but cumbersome and imprecise. The notional tubular maximum for calcium reabsorption (TmCa) has therefore been calculated in 130 healthy young subjects and a normal range of 1.75-2.61 mmol/l of glomerular filtrate established. Owing to the dependence of urinary calcium on urinary sodium, TmCa was negatively related to sodium excretion. Because the latter was higher in the males than the females, mean TmCa was slightly (but not significantly) lower in our male than our female subjects. The normal range of TmCa, corrected to zero sodium excretion, is 1.98-2.76 mmol/l of glomerular filtrate. The TmCa was also calculated using plasma calcium values corrected for albumin concentration. The range of TmCa using both corrections is 1.98-2.71 mmol/l of glomerular filtrate.
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PMID:The tubular maximum for calcium reabsorption: normal range and correction for sodium excretion. 404 67

Patients with recurrent non-infectious calcium urolithiasis were classified metabolically (122 patients). When the magnesium excretion was measured in the metabolic subgroups, a subset of patients (21.6%) could be identified with marked hypomagnesuria as the only metabolic abnormality. A significantly reduced rate of magnesium excretion was found in these normocalciuric stone formers while assessing the overall 24-h urine magnesium excretion or the 24-h urine and fasting urine magnesium to calcium ratio. These differences were apparently not due to factors that might modify renal magnesium excretion, such as parathyroid function, hypercalcemia, hypophosphatemia, alimentary sodium load, age and sex.
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PMID:[Magnesium excretion in recurrent calcium urolithiasis]. 406 Mar 80

The role of parathyroid hormone (PTH) and of Ca(++) in the regulation of bicarbonate absorption (RHCO(3)) and its response to extracellular volume expansion (VE) was studied in HCO(3) (-)-loaded dogs.VE lowered RHCO(3) in both intact (from 24.8 to 22.0 mmol/liter GFR, P < 0.01) and thyroparathyroid-ectomized (TPTX) (from 24.5 to 18.0 mmol/liter GFR, P < 0.001) dogs; glomerular filtration rate (GFR) and filtered HCO(3) (-) did not change. Both groups showed a significant increase in the fractional excretion of sodium (C(Na) x 100/GFR), calcium (C(Ca) x 100/GFR), and chloride (C(Cl) x 100/GFR) and a decrease in phosphorus reabsorption. Fractional clearance of phosphate (C(P) x 100/GFR) rose in both groups but did not achieve significance. Infusion of purified parathyroid extract (PTE) decreased RHCO(3) in intact dogs (from 24.6 to 22.5 mmol/liter GFR, P < 0.025) and in TPTX dogs (from 26.9 to 22.6 mmol/liter GFR, P < 0.05). No change was noted in GFR, renal blood flow (RBF), filtered HCO(3) (-), or fractional excretion of sodium, calcium, or chloride in either group. There was a significant increase in fractional phosphorus clearance and a decrease in phosphorus reabsorption in each group. Infusion of Ca(++) raised ultrafilterable Ca(++) from 5.7 to 7.9 mg/100 ml in intact and from 4.9 to 7.2 mg/100 ml in TPTX dogs; RHCO(3) increased in intact (from 22.9 to 26.9 mmol/liter GFR, P < 0.025) and in TPTX dogs (from 26.6 to 28.6 mmol/liter GFR, P < 0.05). The GFR, RBF, and the fractional excretion of sodium, chloride, and calcium did not change in either group. The reabsorbed phosphate increased in both groups, and fractional phosphorus clearance fell in the intact group but did not change significantly in the TPTX group. Superimposition of PTE on hypercalcemia in TPTX dogs resulted in a decrease in RHCO(3) (from 27.3 to 23.9 mmol/liter GFR, P < 0.001), which was accompanied by an increase in the fractional excretion of phosphate and a decrease in the reabsorbed phosphate. In this group of TPTX dogs hypercalcemia caused a drop in RBF from 135.6 to 105.8 ml/min with no change in GFR. The RBF returned to control value with PTE infusion. IT IS CONCLUDED THAT: (a) the lowering of RHCO(3) by VE is not dependent solely on stimulation of PTH by the lowered Ca(++), (b) PTE acts directly on the renal tubules to lower RHCO(3), (c) Ca(++) enhances RHCO(3) and this effect is exerted in the absence of PTH and calcitonin, (d) neither the effects of Ca(++) nor of PTH appear to be mediated by altered hemodynamics, although this cannot be excluded in Ca(++)-infused TPTX dogs, (e) Ca(++) enhanced phosphate reabsorption in the absence of PTH; this may be a specific effect of hypercalcemia on phosphate reabsorption or the nonspecific consequence of the rise in serum phosphorus.
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PMID:Effects of volume expansion, purified parathyroid extract, and calcium on renal bicarbonate absorption in the dog. 443 33

The urine-concentrating mechanism was studied in chronic hypokalemia (seven dogs given a low K(+), high NaCl diet plus injections of deoxycorticosterone acetate [DOCA]) and chronic hypercalcemia (seven dogs given vitamin D). In the potassium-depleted dogs, muscle, serum, and urine K(+) fell markedly, but glomerular filtration rate (GFR) and body weight varied little. Maximum urine osmolality fell in all dogs (mean decrease = 45%); however, solute-free water reabsorption (T(CH2O)) at high rates of solute excretion remained normal in three of four dogs. Free water excretion (C(H2O)) increased normally or supranormally as a function of increasing Na(+) delivery to Henle's loop in six dogs so tested. Hypercalcemia of several weeks duration caused a decrease in both GFR (mean 36%) as well as in maximum urine osmolality (mean 57%). Maximum T(CH2O) was not invariably depressed; in fact, when the values were adjusted for the reduced number of functioning nephrons (T(CH2O)/C(In)), four of seven studies were normal. C(H20)/C(In) increased normally (or supranormally) with increasing fractional Na delivery to Henle's loop in four of five dogs.I conclude that the lowered maximum urine osmolality in these hypokalemic and hypercalcemic dogs was not related to abnormal water reabsorption from the collecting ducts. Although not specifically measured in this study, it is very likely that solute accumulation in the renal medulla was reduced. This probably was not caused by abnormal delivery of sodium to, nor reabsorption of sodium from Henle's loop. It is likely that a more subtle defect exists in the countercurrent mechanisms for establishing a steep concentration gradient in the renal medulla. In the few hypercalcemic dogs in whom GFR was very low, I believe that injury to, and blockage of medullary tubules could account for most of the reduction in maximum U(Osm). Although not specifically ruled out, there is no evidence here to suggest that high serum Ca(+) or low serum K(+) per se causes a defect in sodium and water reabsorption in the mammalian nephron.
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PMID:Urine concentration and dilution in hypokalemic and hypercalcemic dogs. 543 74

Porcine calcitonin in a slow-release gelatin vehicle was given by intramuscular injection to 10 patients-four with primary hyperparathyroidism, four with Paget's disease, and two with carcinoma of the breast and hypercalcaemia. All cases showed a fall in serum calcium with an immediate rise in urine calcium. All except three patients with primary hyperparathyroidism showed a fall in serum phosphorus, but an immediate rise in urine phosphorus occurred in all cases. Urine hydroxyproline output fell in three patients with severe Paget's disease. Urine sodium rose in all cases, but the effects on potassium, magnesium, water, and pH were not appreciably different from results obtained in four control subjects who were given the gelatin vehicle alone.The data suggest that calcitonin caused a decrease in the tubular resorption of calcium and phosphorus. The hypocalcaemic effect appeared to be due to a decrease in bone resorption in the patients with Paget's disease but in the remaining cases could be accounted for in part or entirely by the rise in urine calcium.
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PMID:Renal effects of calcitonin. 546 Aug 39

Reduced concentrating and diluting capacity of the kidney in acute and chronic hypercalcemia may partly be due to inhibition of transcellular sodium reabsorption (RNa) in the thick ascending limb of Henle's loop. To examine this hypothesis, local heat production and RNa were measured during normo- and hypercalcemia at comparable glomerular filtration rate (GFR) in volume expanded, anesthetized dogs. Changes in proximal RNa which might occur during CaCl2 infusion, were minimized by infusing acetazolamide (75 mg/kg body wt iv). When ultrafiltrable calcium was increased from 1.12 +/- 0.09 to 2.95 +/- 0.10 mmol/l, cortical heat production was unchanged, whereas outer medullary heat production fell by 32 +/- 4%. RNa was reduced by 32 +/- 6%. Bicarbonate reabsorption did not change but calcium reabsorption and potassium excretion increased significantly. The potassium content of cortex and outer medulla increased during hypercalcemia, whereas ouabain, an inhibitor of Na+, K+-ATPase reduces the potassium content. We conclude that hypercalcemia does not inhibit transcellular RNa in the diluting segment by a direct effect on the Na+, K+-ATPase or the mitochondria, but by interfering with the coupled NaCl transport across the luminal cell membrane.
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PMID:Inhibition of transcellular NaCl reabsorption in dog kidneys during hypercalcemia. 609 15

Pharmacological treatment of hypertension can cause clinically significant alterations in endocrine function through effects on glucose homeostasis, thyroid and parathyroid hormones, adrenal steroid metabolism and reproductive/pituitary physiology. Long term use of thiazide diuretics causes deterioration in glucose tolerance, probably secondary to potassium depletion. Hypoglycaemic complications of beta-blockers (mainly the non-selective compounds) can be dramatic, especially in type I diabetics. Clonidine, diazoxide and calcium antagonists have all been associated with deterioration in glucose tolerance and their long term use should be avoided in type II diabetics if possible. Propranolol lowers T3 levels by decreasing the conversion of T4 to T3. Prazosin causes elevations in T4 and thyroid-stimulating hormone, while sodium nitroprusside use may result in hypothyroidism. Numerous agents are associated with sexual dysfunction, including methyldopa, reserpine, clonidine and spironolactone. Thiazide diuretics may cause hypercalcaemia, particularly in patients with hyperparathyroidism, by decreasing urinary calcium as well as directly influencing bone and gut calcium handling. Conversely, propranolol may decrease circulating parathyroid hormone levels and correct the hypercalcaemia seen in hyperparathyroidism. Awareness of drug-induced changes in endocrine function will facilitate the rational management of the hypertensive patient.
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PMID:Effects of antihypertensive drugs on endocrine function. 614 2

Using the ambulatory protocol previously described, 241 patients with nephrolithiasis were evaluated. They could be categorized into 10 groups from the results obtained. Absorptive hypercalciuria type I (87 per cent male) comprised 24.5 per cent and was characterized by normocalcemia, normal fasting urinary calcium (less than 0.11 mg/100 ml glomerular filtration), an exaggerated urinary calcium following an oral calcium load (greater than 0.20 mg/mg creatinine), normal urinary cyclic adenosine monophosphate (AMP) (less than 5.4 nmol/100 ml glomerular filtration) and serum parathyroid hormone (PTH), and hypercalciuria (greater than 200 mg/day during a calcium- and sodium-restricted diet). Absorptive hypercalciuria type II (50 per cent male) accounted for 29.8 per cent; its biochemical features were the same as those for absorptive hypercalciuria type I, except for normocalciuria during a restricted diet and low urine volume (1.42 +/- 0.55 SD liter/day). Renal hypercalciuria (56 per cent male), disclosed in 8.3 per cent, was represented by normocalcemia and high values for fasting urinary calcium (0.160 +/- 0.054 mg/100 ml glomerular filtration), urinary cyclic AMP (6.80 +/- 2.10 nmol/100 ml glomerular filtration) and serum PTH. Primary hyperparathyroidism (57 per cent female), accounted for 5.8 per cent, typically included hypercalcemia, hypophosphatemia, hypercalciuria and high urinary cyclic AMP. Hyperuricosuric calcium urolithiasis (100 per cent male) comprised 8.7 per cent, and was characterized by hyperuricosuria (776 +/- 164 mg/day) and urinary pH exceeding pK for uric acid (5.91 +/- 0.33). In enteric hyperoxaluria (60 per cent female), encountered in 2.1 per cent of cases, urinary oxalate was increased (6.29 +/- 13.2 mg/day). Noncalcium-containing stones were found in 2.1 per cent of the patients with uric acid lithiasis (100 per cent male) and in another 2.1 per cent of the patients with infection lithiasis (60 per cent female). These conditions were typified by low urinary pH (5.29 +/- 0.12) and high urinary pH (6.69 +/- 1.16), respectively. Renal tubular acidosis was found in one patient (male, 0.4 per cent). In 10.8 per cent of the patients (81 per cent male), no metabolic abnormality could be found, although urine volume was low (1.41 +/- 0.51 liter/day). Hypercalciuria could not be differentiated between absorptive hypercalciuria and renal hypercalciuria in 5.4 per cent of the patients. Thus, this ambulatory protocol disclosed a physiologic disturbance in nearly 90 per cent of the cases and provided a definitive diagnosis in 95 per cent of the patients.
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PMID:Ambulatory evaluation of nephrolithiasis. Classification, clinical presentation and diagnostic criteria. 624 14

Severe hypokalemia (2.6 mEq/l), hypomagnesemia (0.6 mg/dl), mild hypercalcemia (10.9 mg/dl), and secondary hyperaldosteronism developed in a patient receiving viomycin for pulmonary tuberculosis. Reversible renal wasting of both potassium (K+) and magnesium (Mg++) was documented. Viomycin administered to 40 rats resulted in severe damage to the proximal tubule and mild damage to the distal tubule. THe case report and experimental data suggest viomycin induces proximal tubule dysfunction that results in renal wasting of sodium, K+ and Mg++ and secondary hyperaldosteronism. Hypercalcemia, not previously associated with viomycin therapy, may be secondary to hypomagnesemia-induced hyperparathyroidism.
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PMID:Viomycin-induced electrolyte abnormalities. 626 92


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