Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a double-blind controlled study, 15 patients received 1,25-dihydroxycholecalciferol (1,25[OH]2D3) (0.5-1.5 microgram/day) and 16 patients received vitamin D3 (D3) (400-1,200 IU/day). The patients receiving 1,25(OH)2D3 had a rise in mean serum calcium concentration from 9.05 +/- 0.15 to 10.25 +/- 0.20 mg/dl (p less than .001) with a return to 9.37 +/- 0.16 (p less than .001) in the post-control period; however, hypercalcemia (greater than 11.5 mg/dl) occurred in 5 of 15 patients. Likewise, patients who received 1,25(OH)2D3 but not those given D3 had a reversible decrease in immunoreactive parathyroid levels. 9 of 12 patients given D3 had serial iliac crest bipsies showing histologic deterioration, while 6 of 7 patients who received 1,25(OH)2D3 were improved or unchanged (p less than 0.025). Bone mineral and calcium content decreased in patients on D3 (p less than .05) but not in those on 1,25(OH)2D3. We conclude that the administration of 1,25(OH)2D3 to dialysis patients: (1) has a calcemic effect. (2) decreases levels of immunoreactive parathyroid hormone, and (3) is associated with histologic improvement in bone disease.
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PMID:Controlled trial of the effects of 1,25-dihydroxycholecalciferol in patients treated with regular dialysis. 624 28

We treated 11 children with vitamin D-resistant rickets with a phosphate mixture either alone (1.2 to 3.6 g per day) or combined with ergocalciferol (vitamin D2, to 50 x 103 IU per day) or with calcitriol (1,25-dihydroxyvitamin D3, 0.25 to 1 microgram per day). Serum calcitriol concentrations were normal in all patients. Calcitriol therapy circulating levels of the hormone to values above normal and increased intestinal phosphate absorption. In some patients this regimen decreased the need for phosphate supplements. None of the treatment regimens corrected the renal phosphate leak. Radiologic studies and bone histomorphometric analyses showed that phosphate (alone or with ergocalciferol) induced the mineralization of the growth plate but not of the endosteal bone surface. Combined calcitriol and phosphate therapy for a total of 2850 patient-days greatly improved the mineralization of trabecular bone. Short-term episodes of hypercalcemia were easily controlled by changes in calcitriol dosage. The data indicate that the combined calcitriol and phosphate regimen is useful in the treatment of vitamin D-resistent rickets.
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PMID:Bone response to phosphate salts, ergocalciferol, and calcitriol in hypophosphatemic vitamin D-resistant rickets. 625 63

Elucidation of the vitamin D endocrine system and the availability of potent metabolites have led to new approaches to vitamin D therapy. The traditional management of exogenous (sunlight) or endogenous (malabsorption) vitamin D deficiency without evidence of disordered vitamin D metabolism has not changed, since it consists of treatment with vitamin D itself--a therapy which preserves the normal intrinsic mechanisms for regulating the rate of production of 1,25-dihydroxycholecalciferol. 1,25-DHCC and the analogue compound 1 alpha-CC should be reserved for treatment of hypocalcemia consequent on chronic renal failure or hypoparathyroidism, where 1-hydroxylation is lacking or impaired. Hypophosphatemic rickets has been treated with 1-hydroxylated compounds, with promising results; this use of the latter metabolites warrants further investigation. The use of vitamin D metabolites and of pharmacological doses of vitamin D itself must be regarded as substitution of a hormone or hormone precursors. Therefore, careful monitoring of serum and urine calcium is required in every patient receiving these compounds, in order to avoid excessive dosage. Special attention must be paid to patients with sarcoidosis since they often develop hypercalcemia after vitamin D or UV-light exposure, as a result of an intrinsic regulation defect in 1,25-DHCC synthesis.
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PMID:[Therapy with vitamin D and D-metabolites]. 626 26

In an attempt to elucidate the influence of 1 alpha-hydroxycholecalciferol (1 alpha OHD3) on parathyroid hormone (PTH) secretion, sequential measurements were made of 1) serum calcium and urinary excretion of cAMP in conscious perfused rats, and 2) serum calcium in nephrectomized rats; also, the effects of a single iv injection of 1 alpha OHD3 on these parameters were examined. In conscious perfused rats, 6.25 micrograms/kg (15 nmol/kg) 1 alpha OHD3 reduced the urinary excretion of cAMP (approximately 40% of the initial value; P less than 0.05), which reached a level compatible with that of parathyroidectomized rats at 4 h; this fall was sustained for 24 h. Serum concentrations of calcium (total and ionized) did not change at 6 h, and increased at 24 h. In parathyroidectomized rats which were continuously infused with bovine PTH (0.75 U/h), the vitamin D preparation had no significant effect on the urinary excretion of cAMP. Nephrectomy, followed by an injection of the vehicle (0.05 ml 99.5% ethanol), induced a transient hypercalcemia (13.12 +/- 0.39 mg/dl at 6 h). This hypercalcemic response was prevented by prior parathyroidectomy. Injections of 1.25 and 6.25 micrograms/kg 1 alpha OHD3 caused a significant suppression of the hypercalcemia (P less than 0.05 and P less than 0.1, respectively) in the presence of parathyroid glands, whereas a dose-related hypercalcemic effect was observed in their absence. These results suggest that in rats, 1 alpha OHD3, either directly or most probably after conversion into 1 alpha, 25-dihydroxycholecalciferol, 1) acutely inhibits PTH secretion without causing a significant rise in serum calcium, and 2) suppresses PTH secretion in secondary hyperparathyroidism induced by nephrectomy.
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PMID:Evidence for acute inhibitory effects in vivo of 1 alpha-hydroxycholecalciferol on parathyroid hormone secretion in rats. 626 31

Vitamin D intoxication was induced in chicks by treatment with large amounts of radioactive cholecalciferol (vitamin D3) either by s.c. injections or by stomach tube. Hypercalcemia and nephrocalcinosis were present, confirming toxicity. The distribution of cholecalciferol and its metabolites in the tissues of the intoxicated birds was compared with that in birds that were treated with physiological amounts of radioactive cholecalciferol. Treatment with pharmacological doses resulted in marked elevation of cholecalciferol and its metabolites in all tissues examined, including elevation of 1 alpha,25-dihydroxycholecalciferol in the intestine. The predominant form of cholecalciferol in these birds was found to be the unchanged vitamin, whereas in birds treated with physiological doses 25-hydroxycholecalciferol was the predominant metabolite. The route of vitamin administration was found to be of importance only when pharmacological doses were given: generally, higher levels were noted when administered via s.c. injections than via stomach tube, except in the arteries. It is suggested that in vitamin D intoxication, the factor responsible for the pathological changes in soft tissues is cholecalciferol itself. High levels of 1 alpha,25-dihydroxycholecalciferol may be responsible for the hypercalcemia.
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PMID:Metabolism of cholecalciferol in vitamin D intoxicated chicks. 628 28

Twenty-seven hypercalcaemic subjects were identified in three generations of a family. There were no clinical complications of chronic hypercalcaemia, but five had had parathyroid surgery which was unsuccessful in four. Twenty of the twenty-seven subjects were compared with twenty-four normocalcaemic controls from the same family and the findings were also compared with those from forty patients with surgically proven primary hyperparathyroidism. The relation between the serum and urinary calcium levels was studied by means of an oral calcium loading test. The ratio of calcium clearance to creatinine clearance was normal in this family (but elevated in the patients with primary hyperparathyroidism) and the concentration of parathyroid hormone was normal, as was the total urinary excretion of cyclic AMP. Thus, there was no evidence of either suppressed or increased parathyroid activity in this familial condition. Basal urinary calcium excretion was normal under steady-state conditions indicating that the hypercalcaemia could not be attributed to either increased bone resorption or increased calcium absorption from the gut. In accordance with this, the serum levels of 1,25-dihydroxycholecalciferol were normal. The hypercalcaemia in this condition can be accounted for in full by an increase in renal tubular reabsorption of calcium, and thus differs from that of primary hyperparathyroidism in which there is increased production of calcium from gut and/or bone as well as an increase in renal tubular reabsorption of calcium. Although the serum phosphate and renal tubular reabsorption of phosphate were both low in patients with familial benign hypercalcaemia, they were not as low as in patients with the same degree of hypercalcaemia due to primary hyperparathyroidism. The changes in phosphate transport in familial benign hypercalcaemia could be explained as a secondary effect of the increased filtered load of calcium in the kidney. The tendency towards hypermagnesaemia in our patients, which contrasts with a tendency towards hypomagnesaemia in primary hyperparathyroidism, could also be explained as a secondary effect of the abnormality of renal tubular reabsorption of calcium. Increased renal tubular calcium reabsorption and persistent normal functioning of the parathyroid glands in the face of hypercalcaemia remain the sole definite abnormalities of the syndrome.
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PMID:Familial benign hypercalcaemia. Study of a large family. 631 Jun 72

Serum vitamin D metabolites, the renal tubular maximum reabsorptive rate for phosphate (TMP/GFR) nephrogenic cyclic AMP (NcAMPI, and CaE (urinary calcium excretion per litre of glomerular filtrate) were measured in 14 adults with familial hypocalciuric hypercalcaemia (FHH). The findings were compared with analyses in 14 patients with surgically proven primary hyperparathyroidism matched for serum calcium, creatinine clearance and vitamin D status (assessed by serum concentrations of 25 hydroxyvitamin D). Vitamin D metabolites were also measured in 16 normocalcaemic relatives of patients with FHH. The serum concentration of 24,25 dihydroxycholecalciferol was appropriate for the prevailing 25 hydroxyvitamin D and no difference was found between groups. The serum concentration of 1,25 dihydroxycholecalciferol was significantly greater in primary hyperparathyroidism (P less than 0.0005) compared with patients with FHH and their normocalcaemic relatives. TMP/GFR was reduced in both primary hyperparathyroidism (0.53 +/- 0.12 mmol/l GF, mean +/- SEM) and FHH (0.86 +/- 0.14 mmol/l GF). Patients with primary hyperparathyroidism showed an increase in NcAMP output in the urine (38.5 +/- 16 mmol/l GF) which was significantly greater (P less than 0.0001) than the normal NcAMP (13.5 +/- 9.2 nmol/l GF) found in FHH. CaE was low in FHH indicating increased renal tubular reabsorption of calcium. It is concluded that there is no abnormality of vitamin D metabolism in FHH comparable with the changes observed in primary hyperparathyroidism. It is suggested that the biochemical abnormalities in FHH cannot be explained solely upon an increased sensitivity of the renal tubules to the effects of endogenous parathyroid hormone.
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PMID:Familial hypocalciuric hypercalcaemia: observations on vitamin D metabolism and parathyroid function. 631 24

Hypercalcemia secondary to malignancies can be divided into two groups according to their calcium elevating mechanism: solid tumors with bony metastases, most frequently originating from the breast or the bronchi, and solid tumors without bony metastases, associated with secretion by the tumor of a substance which increases the calcium level. This substance resembles parathormone in pseudo-hyperparathyroidism, prostaglandins, or other substances not yet identified. The most common tumors involved are bronchial or renal cancers. Diagnostic problems vary depending on whether the cancer has been identified or not, and if bony metastases have or have not been discovered. Primary hyperparathyroidism must also be considered since it is frequently associated with cancer. Hypercalcemia from blood dyscrasias (myeloma and lymphoma) originates from the same mechanisms. It may or may not be associated with bony lesions. The hypercalcemia could be due to a "parathormone like" substance, to prostaglandins, to a substance that stimulates osteoclasts (OAF), or to calcitriol (1,25-dihydroxycholecalciferol). The treatment of hypercalcemia due to malignancies is primarily through the use of antiosteoclastic agents: calcitonin, mithramycin, and more recently diphosphonates. Corticosteroids and the prostaglandin inhibitors can have an additional calcium lowering effect.
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PMID:[Hypercalcemia of cancer and myeloma]. 639 3

A patient with familial hypocalciuric hypercalcaemia (FHH) is reported. Seven years after total parathyroidectomy he remained hypocalcaemic, with biochemical evidence of hypoparathyroidism (enhanced renal tubular reabsorption of phosphate, low nephrogenic cyclic AMP excretion, and reduced serum concentration of 1,25-dihydroxycholecalciferol in the presence of normal renal function and normal serum 25-hydroxyvitamin D levels). Iv infusions of calcium were given before and 6 years after total parathyroidectomy. The renal tubular reabsorption of calcium was compared in these two situations. No difference was found. Before and after parathyroidectomy there was enhanced renal tubular reabsorption of calcium. It is concluded that the enhanced renal tubular reabsorption of calcium in FHH is independent of parathyroid hormone. Total parathyroidectomy corrects the hypercalcaemia in FHH by a reduction in the input of calcium into the extra-cellular fluid from gut and or bone perhaps as a result of reduced renal synthesis of 1,25-dihydroxycholecalciferol.
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PMID:Familial hypocalciuric hypercalcaemia: evidence for continued enhanced renal tubular reabsorption of calcium following total parathyroidectomy. 647 56

Light and electron microscopic characteristics of renal calcification caused by high doses of calcitriol (1,25-dihydroxycholecalciferol) were examined in suckling rats. Four daily doses of calcitriol caused greater hypercalcemia and kidney calcification in 2-week-old than in 3-week-old rats. Calcium deposits, as localized with glyoxal bis(2-hydroxyanil), von Kossa's, or alizarin red S stains, were found primarily in the renal cortex. Glomeruli and tubules were calcified in younger pups, whereas only tubules were affected in older pups. Electron-dense deposits were found primarily in proximal tubules and consisted of needlelike crystals, large mitochondrial granules, and lamellar deposits along basal laminae. The location and appearance of the deposits were similar to those described in vitamin D-treated adult rats. The deposits probably resulted from the hypercalcemia and not from a direct toxic effect of calcitriol on the kidney.
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PMID:Renal calcification in suckling rats after high doses of calcitriol (1,25-dihydroxycholecalciferol). 654 66


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