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Query: UMLS:C0020438 (hypercalciuria)
 2,502 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies have emphasized the pathophysiological importance of circulating 1,25-dihydroxyvitamin D ((1,25-(OH)2D] in the pathogenesis of hypercalciuria and renal stone formation in primary hyperparathyroidism. Reasoning that phosphate administration might be capable of reducing the plasma concentration of 1,25-(OH)2D in patients with a prominent 1,25-(OH)2D-mediated absorptive component to their disease, 10 carefully selected patients were treated with oral phosphate (1500 mg elemental phosphorus daily) for 1 yr. Phosphate treatment significantly reduced circulating 1,25-(OH)2D levels (84 to 56 pg/ml), the calciuric response to an oral calcium tolerance test (0.30 to 0.21 delta mg calcium/dl GF), and calcium excretion on an unrestricted calcium diet (438-269 mg/day), in essence reversing the absorptive pattern of abnormalities observed before treatment. This response, however, was accompanied by an increase in biochemical hyperparathyroidism, as assessed by circulating immunoreactive PTH and nephrogenous cAMP excretion. In patients with biochemical evidence of an increase in bone resorption before therapy, histomorphometric, radiographic, and biochemical data revealed a trend toward a reduction in bone turnover during phosphorus therapy, with an apparent maintenance of coupled bone resorption and bone formation. This trend, however, was of marginal statistical significance in the patient group as a whole. It is concluded 1) that phosphate therapy represents a viable medical alternative in selected patients with primary hyperparathyroidism, 2) that the net response in treated patients is multifaceted and complex, and 3) that the efficacy of phosphate therapy will ultimately depend upon its long term effects on skeletal homeostasis.
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PMID:A detailed evaluation of oral phosphate therapy in selected patients with primary hyperparathyroidism. 630 Jan 78

The authors propose to study parathyroid hormone receptors in humans by means of a test "inspired by the Ellsworth-Howard test" using the active synthetic 1-34 fragment of the hormone PTH-1-34. The use of this test in 44 patients (29 healthy subjects, 7 patients with idiopathic hypercalciuria 5 cases of Paget's disease, 1 patient with idiopathic hypoparathyroidism, 2 cases of basal cell nevus syndrome) who received different doses of this substance intravenously, revealed a marked dose-dependent stimulation of adenyl-cyclase as objectified by an increase in urinary excretion of cyclic AMP (AMPcU). Distal tubular calcium reabsorption was also significantly affected as demonstrated by a decrease in urinary calcium in the first hours following administration of the 1-34 fragment even in the case of idiopathic hypercalciuria. In comparison to the "classical" Ellsworth-Howard test, however, no significant urinary phosphate response was observed during the present test. Similarly, urinary hydroxyproline and phosphate and calcium blood levels remained stable. As the results obtained for the case of hypoparathyroidism demonstrate, this easily performed test is useful for valuating parathormone receptors in kidney by means of two sensitive parameters (AMPcU and the ratio of fractional urinary calcium to urinary creatinine). In addition to its action, synthetic fragment h PTH-1-34 offers the advantage of being totally innocuous.
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PMID:[The effects of synthetic 1-34 fragment of human PTH on kidney and bone receptors in man. Use of the Ellsworth-Howard test]. 631 80

Squamous carcinomas are the most common cause of humoral hypercalcemia of malignancy (HHM) in humans. To develop an animal model of this syndrome, CD-1 female mice were painted with dimethylbenzanthracene, which produced cutaneous squamous carcinomas in the majority of those painted. Greater than 90% of tumor-bearing mice developed a syndrome of hypercalcemia, hypophosphatemia, hypercalciuria, elevated plasma 1,25-dihydroxyvitamin D, normal immunoreactive PTH, elevated urinary cAMP, and accelerated bone resorption compared to control mice. Tumor excision reversed the hypercalcemia and hypophosphatemia, and autopsies revealed no evidence of skeletal or other metastases. Dietary calcium restriction did not affect the hypercalcemia in tumor-bearing mice. Extracts of tumor tissue contained potent bioactivity paralleling that of bovine (b) PTH in a PTH-sensitive canine renal cortical adenylate cyclase assay. The activity was trypsin sensitive and partially inhibitable by Nle, Tyr bPTH amide. The activity coeluted with chymotrypsinogen (mol wt, 25,700) on Sephacryl S-200 chromatography, well ahead of bPTH. This is the first description of an animal squamous carcinoma that produces HHM. With the exception of elevated plasma 1,25-dihydroxyvitamin D levels, the syndrome precisely mimics that seen in human HHM. The presence of a biologically active protein larger than PTH in tumor extracts, similar to that extracted from human tumors, suggests a common mode of pathogenesis. This model should be useful in further studying the pathophysiology of HHM.
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PMID:Squamous carcinoma model of humoral hypercalcemia of malignancy. 649 73

Renal and systemic magnesium metabolism has not been adequately characterized in states of prolonged PTH excess in humans. Whereas acute experimental PTH administration uniformly results in enhanced renal magnesium reabsorption in many species, including humans, numerous clinical reports have documented renal magnesium wasting in human primary hyperparathyroidism. The possibility has been raised, therefore, that secondary consequences of sustained hyperparathyroidism (eg, hypercalcemia, nephrocalcinosis) might override the direct renal effects of PTH. Accordingly, the present studies assessed the effects of chronic (12 days) continuous intravenous (IV) b-(1-34)-PTH infusion in four normal human subjects on plasma, urinary, and intestinal magnesium and calcium homeostasis under metabolic balance conditions. Chronic PTH infusion resulted in a steady-state of hypercalcemia, hypercalciuria, and persistent negative calcium balance, which returned to baseline values in a recovery period. In contrast to plasma calcium concentration, plasma magnesium concentration was not altered by PTH infusion. Significant hypermagnesuria was observed during the period of PTH administration (control, 8.21 +/- 0.43 mEq/24 hours; PTH days 7-12, 10.75 +/- 0.74 mEq/24 hours, P less than 0.05) resulting in an initial, but transient, negative magnesium balance. During days 7-12 of PTH administration, net intestinal magnesium absorption increased sufficiently to result in a return to control magnesium balance. These findings suggest that hypermagnesuria associated with clinical primary hyperparathyroidism results from either direct or indirect effects of PTH excess, per se, and does not require the long-term consequences or complications of the clinical disorder (eg, nephrocalcinosis, renal insufficiency, acidosis).
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PMID:Renal and systemic magnesium metabolism during chronic continuous PTH infusion in normal subjects. 673 67

The state of vitamin D nutrition depends on synthesis in the skin under the influence of sunlight as well as on dietary intake. In European countries that do not fortify milk with vitamin D, reduced sun exposure is the major factor leading to a fall in body stores of vitamin D with age and to a high frequency of hypovitaminosis D in the elderly sick. In the US, because vitamin D is added to milk and the use of vitamin D supplements is more common, the dietary intake of vitamin D is relatively more important than in Europe, and the total vitamin D intake and body stores of vitamin D are generally higher. Nevertheless, body stores of vitamin D probably fall with age in the US as they do in Europe, and it is likely that some sick elderly persons in the US, especially among those confined to institutions, become vitamin D deficient. For several reasons, the vitamin D requirement increases with age, and a total supply of 15 to 20 micrograms/day (600 to 800 IU) from all sources is recommended. Special attention should be paid to persons most likely to need supplementation, such as the housebound, persons with malabsorption, and persons with interruption of the enterohepatic circulation. Osteomalacia, the bone disease produced by severe vitamin D deficiency, is less common in the US than in Europe, but subclinical vitamin D deficiency may contribute to the pathogenesis of hip fractures, both through increased liability to fall and through PTH-mediated bone loss. The extent to which vitamin D deficiency contributes to hip fractures in the US is unknown, and is an important area for future research. Excess intake of vitamin D or of its metabolites may result in hypercalcemia and extra-osseous calcification, particularly in arterial walls and in the kidney, leading to chronic renal failure. The dose of vitamin D that causes significant hypercalcemia is highly variable between individuals but is rarely less than 1000 micrograms/day. Smaller doses can cause hypercalciuria and nephrolithiasis and possibly impaired renal function. Vitamin D administration may raise plasma cholesterol but there is no convincing evidence that the risk of myocardial infarction is increased. The recommended total supply for the elderly of 20 micrograms/day is most unlikely to be harmful, except in patients with sarcoidosis or renal calculi.
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PMID:Vitamin D and bone health in the elderly. 676 68

Since the structural requirements for all known biological activities of parathyroid hormone (PTH(1-84)) are virtually satisfied by the amino-terminal 34 amino acid fragment, PTH(1-34), we investigated whether this fragment could elaborate the overall actions of the intact hormone in the whole animal by comparing the effects of equimolar infusions of each peptide to dogs and rats. Infusion of bovine PTH(1-84) (bPTH(1-84)) at 17 pmol/kg per h for 20 h to three dogs or at 100 and 200 pmol/kg per h to groups of six rats for 5 days produced greater hypercalcaemia (3.02 +/- 0.03, 2.52 +/- 0.07 and 3.24 +/- 0.11 mmol/l respectively) than equimolar infusions of human PTH(1-34) (hPTH(1-34)) (2.61 +/- 0.03, 2.46 +/- 0.05 and 2.71 +/- 0.09 mmol/l respectively). A significant calcium rise was not observed in dogs until after 4 h of PTH infusion. No rise in plasma calcium was apparent in rats, however, until the third day of PTH infusion. Only in parathyroidectomized rats was there a rise in plasma calcium within 24 h of starting an infusion of PTH. The hypercalciuria and plasma phosphate responses in dogs during equimolar infusions of hPTH(1-34) and bPTH(1-84) were not significantly different. However, by day 5 of infusion in rats greater hypercalciuria was produced by bPTH(1-84). Although infusion of hPTH(1-34) and bPTH(1-84) caused rises in urinary cyclic AMP excretion (measured only in the dog) of immediate onset and equal magnitude, bPTH(1-84) tended to produce greater phosphaturia than hPTH(1-34) in both species. If the assumption is correct that the half-lives of hPTH(1-34) and bPTH(1-84) in the circulation are similar and provided that hPTH does not inherently have less biological activity than bPTH, then during equimolar infusions of these peptides into dogs and rats, the greater responses observed with bPTH(1-84) suggest that intact PTH may have a direct action of its own in vivo before being metabolized into smaller biologically active fragments. In additional experiments using parathyroidectomized rats, the infusion rate of bPTH(1-84) required to restore normocalcaemia was 26 pmol/kg per h. Although near-normal calcaemia and intestinal calcium absorption could still be maintained when the infusion rate was increased to 39 pmol/kg per h, hypercalciuria and phosphaturia became apparent.
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PMID:Effects of parathyroid hormone and the synthetic 1-34 amino-terminal fragment in rats and dogs. 684 24

To investigate the pathogenesis of the alterations in bone and mineral metabolism that are found in young insulin-dependent diabetics (IDDs), we performed a standard oral calcium load in 26 IDDs, 7-18 yr of age, and in 17 normal children, 9-18 yr of age. Eighty-five percent of the IDDs had second metacarpal cortical bone widths below the mean for matched controls. Calcium excretion in the IDDs fell along a continuous spectrum, ranging from normal to values consistent with renal hypercalciuria. Immunoreactive PTH was significantly (P less than 0.03) lower in the IDDs compared to that in the controls, and 24,25-dihydroxyvitamin D was significantly elevated (P less than 0.001). We were not able to document a significantly lower concentration of 1,25-dihydroxyvitamin D in the IDDs. Serum calcium, phosphate, and PRL levels were normal, as were creatinine (Cr) clearance and 24-hr urinary cortisol excretion. There was no apparent correlation between the fasting and postload urinary Ca to Cr and glucose to Cr concentration ratios. The accumulated data suggest that in many young IDDs, there is a component of intestinal calcium hyperabsorption which results in appropriate feedback responses by the parathyroid gland and vitamin D metabolic pathway(s). This imbalance between circulating PTH and vitamin D metabolites could result in defective bone remodeling and decreased cortical thickness.
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PMID:Use of oral calcium loading to characterize the hypercalciuria of young insulin-dependent diabetics. 685 83

Of 100 consecutive patients with recurrent renal calculi, 43 had idiopathic hypercalciuria (IH) on outpatient evaluation. Hypercalciuria was classified as diet-dependent or fasting; all patients had normal serum iPTH and urinary cyclic AMP, and serum phosphate and TmPO4/GFR were reduced in IH compared to normocalciuric stone formers. In 16 patients with IH, clearance studies revealed an elevated urine flow are factored for GFR (V/GFR) as compared with normal controls (p less than 0.05). In 12 patients, serum PTH was normally suppressed by calcium infusion but TmPO4/GFR was persistently reduced. Acute and chronic phosphate administration significantly reduced urine calcium excretion but did not correct the abnormal V/GFR. We conclude that in IH of both the fasting and the diet-dependent type, there is a defect in the proximal tubular reabsorption of sodium and fluid as well as PTH-independent tubular phosphate wasting. The proximal tubular defect is not a consequence of hypercalciuria nor of phosphate depletion but may be a cause of these abnormalities.
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PMID:Proximal tubular defects in idiopathic hypercalciuria: resistance to phosphate administration. 716 88

The patient, a 30-year-old woman, was admitted to Itoh Hospital in February, 1979 for hyperthyroidism. She had a history of pyelonephritis and recurrent urinary tract infection. Laboratory data on admission revealed overt hyperthyroidism (T3: 405 ng/dl, T4: 22.5 micrograms/dl and T3U: 57.--%), severe hypercalcemia of 12.6 mg/dl and hypercalciuria. The PSP excretion and GFR were both decreased. Serum c-PTH was nondetectable. As the thyroid function improved, there was a gradual decrease and later normalization of plasma calcium, phosphate and urinary calcium excretion. When subtotal thyroidectomy was performed on October 19, 1979, hypertrophy of the parathyroid gland was not demonstrated. In comparison with 98 other hyperthyroid patients, the pathogenesis of hypercalcemia was discussed. In conclusion, hypercalcemia in the patient, T. Y., was regarded as a kind of disequilibrium hypercalcemia which resulted from a combination of increased bone turnover and decreased calcium excretion by the kidney.
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PMID:A case report on disequilibrium hypercalcemia in hyperthyroidism. Comparison of calcium metabolism with other patients with hyperthyroidism. 717 16

In a group of patients with idiopathic hypercalciuria and an increased fasting urinary calcium excretion we re-examined the question: does secondary hyperparathy-roididsm exist? Eight out of 51 patients with calcium renal stones had a high calcium excretion in both fasting and in 24 h urines. The carboxyl-terminal immunoreactive PTH (iPTH) values in these patients were 16 +/- 5 ngeq/ml (M +/- SD), no higher than the iPTH values in the other groups, e.g. normocalciuric patients had an iPTH of 23 +/- 8 ngeq/ml. The existence of secondary hyperparathyroidism in a subgroup of stone patients with increased fasting urinary calcium excretion is questionable.
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PMID:Parathyroid hormone is normal in renal stone patients with idiopathic hypercalciuria and high fasting urinary calcium. 717 13


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