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)

A 55-year-old patient with hypercalcemic crisis due to gastric carcinoma with bone marrow metastasis was treated with bisphosphonate (pamidronate) and calcitonin. Urinary excretion of parathyroid hormone-related protein (PTHrP) was increased. When normocalcemia had been attained, intravenous hyperalimentation was started, in which 1,000 U vitamin D2 was inadvertently supplemented on days 5-18, On days 15-18, hypercalcemia rapidly recurred, accompanied by markedly increased serum levels of 25-OHD2 (9.1 ng/dl) and 1,25-(OH)2D2 (161 pg/ml). This clinical course suggests that PTHrP, like PTH, stimulated 1 alpha-hydroxylase activity and produced excessive 1,25-(OH)2D2. Vitamin D should not be administered to patients with malignancy-associated hypercalcemia, particularly that due to PTHrP-producing tumors.
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PMID:Increased 1,25-(OH)2D2 concentration in a patient with malignancy-associated hypercalcemia receiving intravenous hyperalimentation inadvertently supplemented with vitamin D2. 801 94

Vitamin D intoxication is a rare cause of hypercalcemia, which is associated with severe and prolonged morbidity. Hypercalcemia and/or hypercalciuria are the consequence of increases in both intestinal absorption and bone resorption. We report on 7 cases of vitamin D overdose (25-hydroxyvitamin D: 710 +/- 179 nmol/l; normal range: 20-90). The indications for vitamin therapy were osteoporosis (5), hypoparathyroidism (1), and osteomalacia (1). Enhanced bone resorption was demonstrated by increased fasting urinary calcium excretion (0.192 +/- 0.067 mmol/l GFR, normal < 0.045). Sequential biochemical measurements in the hypoparathyroid patient showed the persistence of abnormally elevated fasting urinary calcium and of serum 25-hydroxyvitamin D concentrations, even after normalization of plasma calcium, emphasizing that enhanced bone resorption is a prominent feature of vitamin D action. The intravenous administration of a single infusion of the bisphosphonate clodronate to 3 patients led to a correction of hypercalcemia/hypercalciuria, whereas prednisone therapy given to 2 other cases barely affected the abnormal biochemical values. These results indicate that enhanced bone resorption encountered in vitamin D intoxication could be favorably influenced by bisphosphonate treatment.
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PMID:Hypercalcemia and hyperosteolysis in vitamin D intoxication: effects of clodronate therapy. 808 37

Vitamin D topical analogues are now considered an excellent adjunct to the therapy of psoriasis. Systemic vitamin D3 treatment has been used occasionally, especially in case of associated hypocalcemia. We report five patients (aged 6, 16, 36, 58 and 79 years) successfully treated with vitamin D3 per os. Four had erythrodermic and/or pustulous psoriasis, and two of these had concomitant hypocalcemia. The fifth patient was a girl with pseudohypoparathyroidism and psoriasis vulgaris. The association of hypocalcemia and severe psoriasis is classical and was an incentive to try vitamin D treatment. A review of the literature showed that vitamin D can also be reported as a treatment of psoriasis vulgaris. Hypercalciuria and hypercalcemia are limiting risks. However calcium toxicity seems to be minor when vitamin D is given once a day at bedtime in doses lower than 2 micrograms/24 h. Double blind studies should be performed to determine the real efficacy of this treatment.
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PMID:[Treatment of psoriasis by oral calcitriol. A study of 5 cases and review of the literature]. 783 59

A 27-year-old man presented to his dentist with a swelling in his lower jaw. Histology revealed this to be a brown tumour associated with primary hyperparathyroidism and severe but asymptomatic hypercalcaemia. A large parathyroid adenoma was removed and the serum calcium fell to normal. Hypercalcaemia recurred and re-exploration of the neck revealed parathyroid metastases in cervical lymph nodes. A modified radical neck dissection was performed and he has remained normocalcaemic on Vitamin D analogues for 2 years. Bone disease of the mandible is a very rare presentation of primary hyperparathyroidism. The diagnosis of parathyroid malignancy is often difficult histologically, and the optimum treatment is uncertain.
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PMID:Parathyroid carcinoma presenting with a brown tumour of the mandible in a young man. 847 74

Persistent hypercalcemia attributable to parathyroid gland hyperplasia was identified in 6 dogs with primary hyperparathyroidism. Clinical signs included polydipsia (n = 4), polyuria (n = 4), and signs caused by cystic calculi (n = 3). Abnormal clinical pathologic findings included hypercalcemia (mean, 13.6 mg/dl; range, 12.6 to 14.7 mg/dl; n = 6), hypophosphatemia (mean, 2.2 mg/dl; range, 1.4 to 2.9 mg/dl; n = 6), high serum alkaline phosphatase activity (mean, 222 IU/L; range, 161 to 286 IU/L; n = 3), and isosthenuria (mean, 1.012; range, 1.006 to 1.017; n = 6). Serum parathyroid hormone concentration was within the reference range or high (mean, 23 pmol/L; range, 7 to 119 pmol/L; reference range, 1.5 to 13 pmol/L) in all dogs. At surgery, the number of large parathyroid glands was variable, being limited to 1 gland in 3 dogs, 2 glands in 2 dogs, and 4 glands in 1 dog. All visibly large parathyroid glands were surgically removed from each dog. Serum calcium concentration decreased into or below the reference range within 72 hours of surgery in all dogs, confirming the diagnosis of primary parathyroid disease. Multiple nodules of adenomatous hyperplasia were identified in each dog. All 6 dogs were treated with vitamin D and calcium carbonate following surgery. The dog from which all 4 parathyroid glands were removed has remained eucalcemic for more than 1 year with vitamin D supplementation. Vitamin D and calcium administration was discontinued within 4 to 12 weeks of surgery in the remaining 5 dogs. These dogs remained eucalcemic without vitamin D supplementation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Primary parathyroid gland hyperplasia in dogs: six cases (1982-1991). 847 30

Excessive vitamin D causes marked and prolonged hypercalcemia by accelerating intestinal calcium absorption and bone resorption. Vitamin D induced hypercalcemia includes the toxic ingestion of excessive amount of vitamin D preparations, granulomatous diseases and lymphoproliferative malignancies. In vitamin D toxicity, the clinical courses vary depending on the vitamin D preparation responsible for the hypercalcemia. Hypercalcemia state continues for several months when D2 or D3 are responsible for the toxicity whereas the hypercalcemia would subside in a week when 1 alpha(OH) D3 or 1,25 (OH)2D3 are responsible for the toxicity. Abnormal calcium metabolism can be treated by hydration and glucocorticoids. Hypercalcemia is associated with variety kinds of granulomatous diseases, including sarcoidosis and tuberculosis. The granulomatous tissue is believed to be the site of the ectopic production of 1,25(OH)2D3 in which the regulation of the synthesis is quite different from that in the normal kidney. Glucocorticoid markedly diminishes the synthesis. Hypercalcemia associated with elevated serum 1.25(OH)2D3 levels is also found in patients with lymphomas and some other malignancies. However, there still are not sufficient evidences to prove that the excessive amount of endogenous 1.25(OH)2D3 is the primary cause of the hypercalcemia.
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PMID:[Hypervitaminosis D]. 848 81

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

Vitamin D has been discovered at the beginning of this century. 7-Dehydrocholesterol is converted to vitamin D3 in the skin and after several hydroxylations it is further converted to the active hormonal form, 1 alpha,25-(OH)2D3. Vitamin D stimulates the absorption of calcium and phosphate and is an essential link in bone resorption and formation and calcium metabolism. 1 alpha,25-(OH)2D3 acts through a vitamin D receptor. These receptors are not only present in clinical target organs (kidney, gut, liver) but can also be found in a wide variety of "non-classical" tissues (keratinocytes, cells belonging to the immune system). Moreover, numerous cells (keratinocytes, macrophages) can locally synthetize or can be induced to synthetize 1 alpha,25-(OH)2D3 and these cells are responsive to its action. When these data are combined, a possible paracrine function of 1 alpha,25-(OH)2D3 can be suspected. Via this paracrine function 1 alpha,25-(OH)2D3 can suppress the cellular and humoral immunity. Based on the discovery of these effects on immune cells in vitro it became clear that 1 alpha,25-(OH)2D3 might be an interesting molecule to prevent autoimmune diseases and organ transplantation. This has already been shown in several animal models (Heymann nephritis, diabetes mellitus, experimental allergic-encephalomyelitis, lupus). 1 alpha,25-(OH)2D3 demonstrates however some side-effects (hypercalciuria, hypercalcemia, bone resorption) and for this reason 1 alpha,25-(OH)2D3-analogs are developed with dissociated effects i.e. an activity profile that allows a specific action on non-classical tissues without calcemic effects. Some chemical modifications of the side chain, A and/or CD-ring results in "superanalogs" with 10 to 100-fold more activity on cell differentiation and the immune system then 1 alpha,25-(OH)2D3 but with less calcemic activity in vivo. These biological effects can be explained by differences in pharmacokinetics (low affinity for the plasma vitamin D-binding protein and short extracellular half-life) and increased intracellular activation and gen transactivation. Preclinical research must still be done to select the most potent superanalogs and to find the exact protocols for the prevention and treatment of autoimmune diseases and rejection of transplanted organs.
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PMID:[Immune modulation by vitamin D analogs in the prevention of autoimmune diseases]. 857 69

Fat soluble vitamins (except vitamin K) are protein bounded with subsequent storage in the body. It is generally accepted that plasma level of vitamin A is increased in majority of patients with chronic renal insufficiency (CRI) including those on continuous ambulatory peritoneal dialysis (CAPD). Thus, there is no need to supplement this vitamin in CRI patients (pts). Plasma level of vitamin E in CRI pts may be elevated, normal or decreased. It seems to be justified to supplement this vitamin, in spite of its normal plasma level, in case platelet aggregation is increased. Both in dialyzed and nondialyzed CRI pts a normal serum level of vitamin K has been observed. Decreased or extremely low serum level of vitamin D following the gradual loss of renal tissue is to be observed in CRI pts. This deficit is regarded as the main factor leading to the decrease in serum level of calcium, the secondary hyperparathyroidism and bone changes. Treatment with 1.25(OH)2D3 (calcitriol) proved to be most successful in alleviation of symptoms resulting from the deficit of vitamin D3 in the body. Intravenous "pulsating" administration of calcitriol results in rapid normalization of serum PTH level. Treatment with 25(OH)D3 (calcidiol) given orally 3 times a week ("pulsating" method) revealed also fairly good results in this respect. During treatment with vitamin D3 hypercalcemia tends to develop, serum alkaline phosphatase normalizes, elevated PTH serum level decreases. Vitamin D metabolites are less active than 1.25(OH)2D3 being less hypercalcemic.
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PMID:[Vitamin disturbances in chronic renal insufficiency. II. Fat soluble vitamins]. 871 Nov 72

The efficacy of subtotal parathyroidectomy (n = 11), total parathyroidectomy+autotransplantation (n = 13) and total parathyroidectomy alone (n = 24) were compared in a series of renal patients with hyperparathyroidism. The principal indication for surgery was severe bone disease but other indications were uncontrolled hypercalcaemia, soft tissue calcification and grossly elevated parathyroid hormone (PTH) levels. The clinical success rates at 24 months follow-up for subtotal, total plus autograft, and total parathyroidectomy were 100, 89 and 97% respectively. Similar improvements in radiological changes and alkaline phosphatase levels were seen in all three groups. Recurrent hyperparathyroidism was recorded in three (27%) members of the subtotal parathyroidectomy group and two (16%) of the patients undergoing total parathyroidectomy and autotransplantation. Two patients required re-exploration of their forearm parathyroid autograft. No patients undergoing total parathyroidectomy only suffered persistent or recurrent hypercalcaemia. Vitamin D analogue requirements rates in patients undergoing subtotal, total plus autotransplant, and total parathyroidectomy at 24 months were 44, 70 and 81% respectively. An important finding is the demonstration of residual parathyroid function in 14/16 patients (87.5%) undergoing total parathyroidectomy without autotransplantation and followed-up for 2 years.
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PMID:Parathyroidectomy in chronic renal failure: comparison of three operative strategies. 962 48


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