Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020438 (hypercalciuria)
 2,502 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies were conducted in a patient with idiopathic hypophosphatemic osteomalacia to delineate the roles of parathyroid hormone (PTH), vitamin D and renal tubular function. A 43-year-old woman presented with progressive skeletal pains resulting in severe incapacity. Workup revealed: hypophosphatemia with a low tubular maximal phosphate reabsorption per glomerular filtrate (TmP/GFR) of 1.05 mg/dl, normocalcemia, hypocalciuria, elevated alkaline phosphatase and glycinuria. PTH and urinary cyclic AMP (UcAMP) were normal, while calcitriol was low. Renal tubular acidosis or other transport defects were not present and no tumor was found. Biopsy was diagnostic for osteomalacia, and the patient responded to 1-alpha OHD3 and phosphate therapy. Hyperparathyroidism was ruled out by 1) normocalcemia persisting after 1-alpha OHD3 and calcium loading and 2) normal PTH and UcAMP challenged by phosphate supplements. Combined calcium and 1-alpha OHD3 administration resulted in hypercalciuria, decreased UcAMP and increased, but not corrected, TmP/GFR. These findings suggest that the osteomalacia was due to hypophosphatemia caused by a renal leak. PTH is only contributory to the phosphaturia. Low calcitriol level contributes to the osteomalacia directly and indirectly through impaired mineral absorption and, therefore, is also responsible for the hypocalciuria.
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PMID:Metabolic studies in a patient with idiopathic hypophosphatemic osteomalacia. 334 50

In male healthy controls (n = 12), male renal calcium stone patients with either normocalciuria (NC; n = 12) or idiopathic hypercalciuria (I-HC; n = 12), all ideally matched for age and body weight, the response of variables of mineral metabolism to a calcium-rich oral test meal was evaluated. In all groups the postprandial urinary cyclic AMP is decreased as compared with fasting urine, indicating that the parathyroid glands are suppressible by oral calcium. However, in I-HC serum total calcium was significantly higher than in controls both basally and in the postprandial period; the associated mid-regional (bioinactive) serum parathyroid hormone was also elevated, but serum parathyroid hormone recognizing the amino terminal (bioactive) region of the molecule was significantly decreased. Also in I-HC, serum alkaline phosphatase is elevated, whereas urinary hydroxyproline in both fasting and postprandial urine is unchanged. The NC group holds an intermediate position between I-HC and controls. It can be concluded that I-HC subjects may suffer from a more basic disturbance of calcium metabolism which may help explain the nature of their hypercalciuria.
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PMID:Fasting and post-calcium load serum calcium, parathyroid hormone, calcitonin, in male idiopathic calcium urolithiasis--evidence for a basic disturbance in calcium metabolism. 366 61

To clarify the mechanism for the impaired mineral metabolism in Cushing's syndrome, the clinical features, biochemical parameters before and after oral calcium load, and vitamin D metabolism were compared between two groups of patients of endogenous Cushing's syndrome (17 cases) with and without osteopenia. The patients with osteopenia [OP (+): 7 cases, all female] were older (42.7 +/- 8.3 y. o.) and had a longer duration (117 +/- 75 M) of the syndrome than those without osteopenia [OP (-): 33.8 +/- 8.9 y. o., 36 +/- 25 M]. OP (-) showed a blunted hypercalciuria after oral calcium load (63.7 +/- 20.4 to 90.9 +/- 36.1 mg/g X Cr), while OP (+) had higher levels of urinary excretion of calcium (fasting: 120.4 +/- 37.5, and after oral calcium load: 235.6 +/- 72.6 mg/g X Cr), of cyclic AMP (7.6 +/- 1.1 nmol/dl X GF), and of plasma 1.25(OH)2D (76.6 +/- 34.0 pg/ml) than OP (-) (u-cAMP: 3.2 +/- 2.0 nmol/dl X GF, 1,25(OH)2D: 27.9 +/- 16.3 pg/ml). These results indicate that 1) elderly female patients with Cushing's syndrome of long duration are susceptible to OP, 2) during the early phases of the syndrome, reduced intestinal calcium absorption with sustained calciuria (probably through the inhibition of calcium reabsorptive effect of PTH by glucocorticoid) induces negative calcium balance, leading to 3) a development of secondary hyperparathyroidism which stimulates 1,25(OH)2D synthesis. Thus, the mechanism involving bone resorption stimulated by excess PTH along with the direct inhibition of bone formation by glucocorticoid seems to play an important role in a progressive development of OP in Cushing's syndrome.
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PMID:Impaired mineral metabolism in Cushing's syndrome: parathyroid function, vitamin D metabolites and osteopenia. 375 23

The stimulation of cyclic AMP production by human renal cortical membranes in the presence of the GTP analogue 5'-guanylimidodiphosphate and a calcium chelator represents a homologous assay system for the evaluation of biologically active parathyroid hormone (bioPTH) in human serum. Bioactive PTH was raised above normal (normal range: undetectable to 4.6 pmol human PTH(1-34) per 1) in 13/17 (76%) patients with primary hyperparathyroidism, in 5/6 (83%) patients with surgically proven hyperparathyroidism secondary to chronic renal failure, in 4/5 (80%) patients with hyperparathyroidism secondary to hypocalcaemia, in all three patients with pseudohypoparathyroidism, in 5/17 (29%) patients with osteoporosis and in 1/9 (11%) patients with renal stones and/or hypercalciuria. Bioactive PTH correlated positively with immunoreactive PTH (iPTH) measured with a radioimmunoassay predominantly recognizing the middle- and carboxyl-terminal region of the PTH molecule (r = 0.503, P less than 0.001). A positive correlation (r = 0.572, P less than 0.05) was found between values of serum calcium and bioPTH in the group with primary hyperparathyroidism. Immunoreactive PTH did not correlate significantly with calcium in this group. In the other patients except those who had chronic renal failure, a negative correlation between serum calcium and both bioPTH and iPTH was observed (P less than 0.01). When alkaline phosphatase was compared with bioPTH in all patients, the correlation was positive (r = 0.390, P less than 0.01); no significant correlation existed between iPTH and alkaline phosphatase in the patients studied.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal adenylate cyclase assay for biologically active parathyroid hormone: clinical utility and physiological significance. 394 39

The causes for the hypercalciuria and diagnostic criteria for the various forms of hypercalciuria were sought in 56 patients with hypercalcemia or nephrolithiasis (Ca stones), by a careful assessment of parathyroid function and calcium metabolism. A study protocol for the evaluation of hypercalciuria, based on a constant liquid synthetic diet, was developed. In 26 cases of primary hyperparathyroidism, characteristic features were: hypercalcemia, high urinary cyclic AMP (cAMP, 8.58+/-3.63 SD mumol/g creatinine; normal, 4.02+/-0.70 mumol/g creatinine), high immunoreactive serum parathyroid hormone (PTH), hypercalciuria, the urinary Ca exceeding absorbed Ca from intestinal tract (Ca(A)), high fasting urinary Ca (0.2 mg/mg creatinine or greater), and low bone density by (125)I photon absorption. The results suggest that hypercalciuria is partly secondary to an excessive skeletal resorption (resorptive hypercalciuria). The 22 cases with renal stones had normocalcemia, hypercalciuria, intestinal hyperabsorption of calcium, normal or low serum PTH and urinary cAMP, normal fasting urinary Ca, and normal bone density. Since their Ca(A) exceeded urinary Ca, the hypercalciuria probably resulted from an intestinal hyperabsorption of Ca (absorptive hypercalciuria). The primacy of intestinal Ca hyperabsorption was confirmed by responses to Ca load and deprivation under a metabolic dietary regimen. During a Ca load of 1,700 mg/day, there was an exaggerated increase in the renal excretion of Ca and a suppression of cAMP excretion. The urinary Ca of 453+/-154 SD mg/day was significantly higher than the control group's 211+/-42 mg/day. The urinary cAMP of 2.26+/-0.56 mumol/g creatinine was significantly lower than in the control group. In contrast, when the intestinal absorption of calcium was limited by cellulose phosphate, the hypercalciuria was corrected and the suppressed renal excretion of cAMP returned towards normal. Two cases with renal stones had normocalcemia, hypercalciuria, and high urinary cAMP or serum PTH. Since Ca(A) was less than urinary Ca, the hypercalciuria may have been secondary to an impaired renal tubular reabsorption of Ca (renal hypercalciuria). Six cases with renal stones had normal values of serum Ca, urinary Ca, urinary cAMP, and serum PTH (normocalciuric nephrolithiasis). Their Ca(A) exceeded urinary Ca, and fasting urinary Ca and bone density were normal. The results support the proposed mechanisms for the hypercalciuria and provide reliable diagnostic criteria for the various forms of hypercalciuria.
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PMID:The hypercalciurias. Causes, parathyroid functions, and diagnostic criteria. 436 91

A family of idiopathic hypercalciuria (IH), 3 symptomatic and 2 asymptomatic, plus 3 normal subjects were given the 1 Gm oral calcium challenge. Biochemical parameters measured included: serum and urinary calcium and phosphate, urinary cyclic AMP, and serum intact and carboxyl-terminal parathyroid hormone. Major differences between the normal control and the family with IH include: (1) higher calcemic response in the family with IH (0.9 vs 0.4 mg/dl); (2) a fall in carboxyl-terminal PTH and urinary cyclic AMP in the IH family in contrast to control subjects in whom there were no changes; (3) a rise in serum phosphorus in the IH family (0.8 vs 0.2 mg/dl, p less than 0.05). Urinary excretion of calcium, phosphorus, and sodium after the calcium challenge was minimal. The oral calcium challenge is a simple and useful test in demonstrating increased calcium absorption even in asymptomatic relatives of patients with idiopathic hypercalciuria.
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PMID:Altered responses in serum calcium phosphorus and parathyroid hormone to oral calcium load in symptomatic and asymptomatic members of family with idiopathic hypercalcemia. 608 33

With oral furosemide administration and salt loading, urinary calcium was significantly increased in 8 normal subjects, accompanied by parallel natriuresis. In spite of the excessive calcium loss in the urine, total and ionized serum calcium remained unchanged. All subjects had significant increases in nephrogenous cyclic AMP, suggesting that parathyroid activity is elevated in subjects with furosemide-induced hypercalciuria. With furosemide, fecal calcium was significantly decreased, and resultantly, there was no significant change in the cumulative calcium balance. It is suggested that urinary calcium loss with furosemide is compensated for by secondary hyperparathyroidism via increased intestinal calcium absorption in order to maintain serum calcium at a normal level. The experimental model thus mimics the condition of the renal type of idiopathic hypercalciuria.
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PMID:Effects of oral furosemide and salt loading on parathyroid function in normal subjects. Physiological basis for renal hypercalciuria. 608 14

The role of 1,25-dihydroxyvitamin D (1,25(OH)2D) in the pathogenesis of idiopathic hypercalciuria was studied in 37 renal stone formers who, during two 10-day periods, followed first a normal and then a low calcium diet. The following samples were taken during each diet; 24 h urine; fasting blood and urine; blood and urine following a 1 g oral calcium load. Patients were divided according to serum calcium level, 24 h urinary calcium excretion on the first diet and fasting calcium excretion on the second diet. Eight patients were found to be normocalciuric (NSF), 16 had absorptive hypercalciuria (AH), five renal hypercalciuria (RH) and eight primary hyperparathyroidism. In NSF and AH, a positive correlation was found between the fasting and the 24 hour urinary calcium (r = 0.787, P less than 0.001), while negative correlations were found between the fasting urinary calcium and the serum parathyroid hormone (r = -0.703, P less than 0.001) or the fasting urinary cyclic AMP (r = -0.434, P less than 0.01). Patients with RH had higher serum PTH and urinary cAMP levels for a given degree of fasting calciuria mainly on the low calcium diet. Mean serum 1,25(OH)2D was similar in NSF (43.6 +/- 4.5 pg/ml), AH (43.6 +/- 2.3 pg/ml) and RH (40.4 +/- 4.8 pg/ml) on the first diet; increases were similar in all groups after 10 d of calcium restriction. A positive correlation was found between the serum 1,25(OH)2D concentrations and the 24 h urinary calcium excretion on the first diet in NSF (r = 0.889, P less than 0.001) but not in AH or RH. There was no evidence of such correlation with the low calcium diet. No correlation between the calciuric response to calcium loading and the serum concentrations of 1,25(OH)2D was found. The results suggest that serum concentrations of 1,25(OH)2D may be related to urinary calcium excretion in NSF more than in AH or RH. The factors responsible for the hyperabsorption of calcium in the latter patients remain to be elucidated.
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PMID:Influence of dietary calcium on serum 1,25-dihydroxyvitamin D concentrations in renal stone formers. 609 46

The availability of accurate and inexpensive methods for measuring serum calcium levels has resulted in a rapid increase in the number of diagnoses of primary hyperparathyroidism, notably in its asymptomatic hypercalcemic forms. In addition, the development of a radioimmunoassay of the parathyroid hormone and, more recently, measurements of nephrogenous cyclic AMP during fasting and after calcium loading have led to the recognition of clinical variants of the disease, such as intermittent or borderline hypercalcemia and pure hypercalciuria with normal calcemia. The degree of hypercalcemia in stable primary hyperparathyroidism depends on renal tubular reabsorption of calcium rather than on bone resorption. The poor correlation observed between calcium tubular reabsorption rate and magnitude of parathyroid hormone hypersecretion suggests that as yet undetermined factors interfere with the effects of parathyroid hormone on renal tubules and probably account for the fluctuations in calcemia reported during serial determinations in patients. The sigmoid relationship between parathyroid hormone release and extracellular calcium concentrations has been analyzed from recent in vitro studies with dispersed parathyroid cells. In primary hyperplasia of the parathyroid glands hypersecretion of parathyroid hormone seems to depend principally upon the increase in tissue mass with normal sensitivity to calcium at cellular levels, whereas in adenoma the primary abnormality responsible for hypersecretion of parathyroid hormone would be an alteration in cell sensitivity to calcium, as indicated by an elevated "set point". Finally, while complicated primary hyperthyroidism requires surgery, our limited knowledge of the natural history of asymptomatic forms makes it impossible to decide which of these patients will ultimately need to be operated upon.
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PMID:[Present status of primary hyperparathyroidism]. 623 8

Ten patients with subtle primary hyperparathyroidism and intermittent hypercalcaemia were followed serially for periods of 2--18 months (mean 10 months). Fasting serum calcium was elevated (greater than 10.6 mg/dl) in only 20% of determinations and fluctuated widely (9.1--11.2 mg/dl), yet the patients displayed a continuous, rather than episodic, basic disease process as defined by increases in nephrogenous cyclic AMP and serum iPTH. Identical findings were noted in short-term (2--3 successive days) studies in twelve patients. In response to a 1000 mg oral calcium tolerance test, twelve patients with primary hyperparathyroidism and intermittent hypercalcaemia (basal serum calcium 10.2 +/- 0.2 mg/dl, mean +/- SD) displayed: (1) hyperabsorption of calcium (mean calciuric response twice normal); (2) induced-hypercalcaemia (mean serum calcium 11.4 mg/dl, with a mean increase of 1.2 mg/dl versus 0.2 mg/cl in normal subjects); and (3) abnormal parathyroid suppressibility (nephrogenous cyclic AMP 2.66 +/- 0.57 nmol/100 ml GF versus 0.95 +/- 0.40 nmol/100 ml GF in normal subjects, mean +/- SD). The patients demonstrated striking hypercalciuria (452 +/- 123 mg/24 h) on a 1000 mg metabolic calcium diet. Serum levels of 1,25(OH)2D3, measured in ten patients, were markedly elevated at 90 +/- 20 pg/ml (mean +/- SD), and there was a strong positive correlation between the values for 1,25(OH)2D3 and the calciuric response to the calcium tolerance test (r = 0.75, P less than 0.001). These results (1) indicate that the calcium tolerance test is a simple and reliable technique for diagnosis of patients with primary hyperparathyroidism and intermittent hypercalcaemia, and (2) emphasize the important pathophysiologic features of this subtle clinical variant of primary hyperparathyroidism.
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PMID:Primary hyperparathyroidism with intermittent hypercalcaemia: serial observations and simple diagnosis by means of an oral calcium tolerance test. 624 72


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