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)

Pseudohypoparathyroidism (PHP) is a hereditary disorder with typical dysmorphic signs, oligophrenia and clinical and laboratory signs of hypoparathyroidism, which is resistant to parathyroid extract (PTE). Pseudopseudohypoparathyroidism (PPHP) is a genetically identical, partial form of PHP without hypoparathyroidism. Many hypotheses exist to explain the pathogenesis of these disorders: Albright and coworkers first demonstrated the PHP is caused by an inability of the renal tubules to respond to parathyroid hormone (PTH). Later hypotheses proposed a general defect in phosphorus transport, defects in the synthesis of PTH, the existence of antibodies to this hormone or hyperthyrocalcitonism. The possibility of measuring PTH in the peripheral serum by radioimmunoassay and improved knowledge of the role of cyclic adenosine monophosphate (cAMP) as a mediator of the action of PTH were necessary to explain the pathogenesis of PHP and PPHP. Three children suffering from PHP and two adults with PPHP were investigated as follows: measurements of PTH in the peripheral serum; assays of PTH levels during artificial hypercalcaemia; serial assays of calcium, phosphorus and PTH levels during vitamin D treatment; changes in the Ellsworth-Howard tests indicative of PTE resistance during vitamin D treatment and measurements of urinary cAMP excretion before and during vitamin D therapy. The following results were obtained: Secondary hyperparathyroidism in PHP, which could be suppressed by hypercalcaemia; normal levels of PTH in PPHP; normalization of serum calcium, phosphorus and PTE during treatment with vitamin D; abnormally low basal levels of cAMP in PHP, which could not be stimulated by PTE either before or during vitamin D treatment. The results of these investigations confirm Albright's hypothesis of endorgan resistance to PTH in PHP. This is caused by the inability of the PTH-sensitive adenylcyclase-system to mediate the action of PTH on its target cells. This is responsible for the distrubances in calcium and phosphorus metabolism and for secondary hyperparathyroidism. While this mediatorial defect seems to be total or almost total in PHP, a partial defect has to be assumed in PPHP.
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PMID:[Pseudohypoparathyroidism: investigations of the serum parathyroid hormone level, pte resistance and urinary camp excretion before and during vitamin d treatment (author's transl)]. 17 30

76 kidney transplant recipients who were up to 4 years post transplant, were studied to assess the incidence of secondary hyperparathyroidism. All patients had good renal function with a mean serum creatinine of 1.4 mg/100 ml. Secondary hyperparathyroidism, as evidenced by increased serum parathyroid hormone levels, was present in 53 of the 76 patients (66%) and radiologic bone disease in 26 of the 76 patients (34%), while hypercalcemia (serum calcium greater than 11.0 mg/100 ml) occurred in only 6 patients (8.5%). The incidence of secondary hyperparathyroidism decreased slightly with time following transplantation, but the degree of secondary hyperparathyroidism as indicated by the levels of serum parathyroid hormone at various times following renal transplantation was essentially similar. The causes for the persistence of this condition are not totally known, but it was found that its incidence was related to the duration of dialysis prior to transplantation.
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PMID:Secondary hyperparathyroidism in human kidney transplant recipients. 78 18

Five patients with haemodialysis bone disease were treated with 1 to 1.5 mug of 1,25 (OH)2D3 daily for periods ranging from 6 -8 months. There was a significant improvement in calcium absorption but no troublesome hypercalcaemia was encountered. Secondary hyperparathyroidism improved, both histologically and radiologically, and there was a fall in serum PTH and return of serum alkaline phosphatase to within normal limits. There was also improvement in the patients' mineralisation status, but this change was slower and less marked. Muscle power improved significantly, both clinically and electromyographically.
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PMID:Long term therapy with 1,25(OH)2D3 in dialysis bone disease. 93 16

The relative contributions of Ca++, phosphorus, and parathyroid hormone (PTH) on insulin secretion were evaluated in three groups of dogs. Dogs were studied with glucose infusions (group I) or standard intravenous glucose tolerance tests (IVGTT) (group II) before and after the development of diet-induced hypophosphatemia. Mean serum phosphorus levels for both groups fell from 4.1 to 1.1 mg/100 ml. Animals in group I demonstrated a fall in glucose disappearance rates (Kg) from 5.3+/-0.6% min to 3.5+/-0.5% after induction of hypophosphatemia (P less than 0.001). Mean insulin response was significantly greater in the hypophosphatemic animals than in controls in this group. In group II animals, mean insulin areas obtained during the IVGTT increased from 1,426+/-223 to 2,561+/-141 muU/ml/60 min after induction of hypophosphatemia, and were unaffected by Ca++ or PTH administration. Ca++ administration, but not hypophosphatemia or PTH infusion, increased significantly the mean insulin response to tolbutamide. Secondary hyperparathyroidism was induced by dietary manipulation in four dogs (group III). Mean PTH values increased from 71.4+/-2.1 to 3,012+/-372 pg/ml (P less than 0.001). Mean insulin response to an IVGTT was similar to group III animals, but increased from 1,352+/-128 to 1,894+/-360 muU/ml/60 min after the excessive dietary phosphorus was reduced for 3 mo, and plasma phosphorus fell from 3.2+/-0.1 to 2.8+/-0.3 mg/100 ml. PTH values decreased to 647+/-53 pg/ml. The insulin response to tolbutamide was comparable to that in group II animals, but increased significantly after calcium administration. Immunoreactive insulin disappearance rates were unaffected by hypophosphatemia or diet-induced secondary hyperparathyroidism. These data demonstrate that hypophosphatemia is associated with an augmented glucose-stimulated insulin release, without any effect on tolbutamide-stimulated insulin release. Hypercalcemia produces an augmented tolbutamide-stimulated insulin release with no apparent effect on glucose-stimulated insulin release. Finally, PTH does not appear to be an insulin antagonist and has no apparent effect on either glucose- or tolbutamide-stimulated insulin release in animals with dietary-induced secondary hyperparathyroidism.
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PMID:The relative roles of calcium, phosphorus, and parathyroid hormone in glucose- and tolbutamide-mediated insulin release. 95 71

Bone and joint pathology in patients undergoing long-term dialysis for end-stage renal failure is presented in the light of typical cases and a brief review of the literature. Osteomalacia with bone pain and fractures is caused mainly by aluminium overload due to enteral uptake from aluminium-containing phosphate binders. This is why calcium acetate or calcium carbonate should be used exclusively to lower enteral phosphate reabsorption. If--due to hypercalcemia--aluminium containing phosphate binders--cannot be entirely avoided, they should never be administered together with citrate (citrate-containing medication, fruit juice, etc.), which chelates aluminium and thereby massively increases enteral aluminium uptake. Secondary hyperparathyroidism with overt radiologically demonstrable bone disease develops in many patients on long-term dialysis despite efforts to maintain plasma calcium within or slightly above the upper normal range and concomitant treatment with calcitriol. Intravenous administration of relatively high-dose calcitriol or 1-alpha-OH-D3 (neither readily available at the present time), as well as the newly developed experimental vitamin D analogs such as 22-oxa-(OH)2-D3, which appear to suppress the parathyroid glands without increasing enteral calcium reabsorption, may in future reduce the high incidence of parathyroidectomy in patients on maintenance dialysis. beta 2-microglobulin amyloidosis is a new disease entity which develops in the majority of long-term dialysis patients. Apart from carpal tunnel syndrome, trigger fingers and tendon ruptures, it is associated with acute and chronic painful erosive arthropathy with joint effusions and fractures, particularly around the hip, due to cystic bone lesions where bone is replaced by nodular amyloid deposits.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Bone and joint problems in long-term dialysis]. 159 6

Secondary hyperparathyroidism is common in dialysis patients. Intravenous calcitriol has proven to be an effective therapy for the reduction of parathyroid hormone (PTH) levels. However, the effect of i.v. calcitriol on parathyroid function, defined as the sigmoidal PTH-calcium curve developed during hypocalcemia and hypercalcemia, has not been evaluated during the prolonged administration of i.v. calcitriol. Six hemodialysis patients with marked secondary hyperparathyroidism, PTH levels greater than 500 pg/mL (normal, 10 to 65 pg/mL), were treated for 42 wk with 2 micrograms of i.v. calcitriol after each hemodialysis. Parathyroid function was evaluated before and after 10 and 42 wk of calcitriol therapy. Between baseline and 42 wk, the basal PTH level decreased from 890 +/- 107 to 346 +/- 119 pg/mL (P less than 0.02) and the maximally stimulated PTH level decreased from 1293 +/- 188 to 600 +/- 140 pg/mL (P less than 0.01). In addition, calcitriol administration significantly decreased PTH levels throughout the hypocalcemic range of the PTH-calcium curve. Although the slope of the PTH-calcium curve (with maximal PTH as 100%) decreased between baseline and 42 wk (P less than 0.05), the set point of calcium did not change. Two patients with a decrease in both basal and maximally stimulated PTH levels after 10 wk of calcitriol, developed marked hyperphosphatemia between 10 and 42 wk; this resulted in an exacerbation of hyperparathyroidism despite continued calcitriol therapy. In conclusion, prolonged i.v. calcitriol administration is an effective treatment for secondary hyperparathyroidism in hemodialysis patients provided that reasonable control of the serum phosphate is achieved. In addition, the slope of the PTH-calcium curve may be a better indicator of parathyroid cell sensitivity than the set point of calcium.
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PMID:The effect of long-term intravenous calcitriol administration on parathyroid function in hemodialysis patients. 176 May 37

Secondary hyperparathyroidism (HP) is well known complication of long-term uremia. CAPD patients show a peculiar behaviour due to loss of vitamin D metabolites through peritoneum. Severe degrees of hyperparathyroidism may require parathyroidectomy in order to achieve appropriate control. Recently, the possibility of controlling this situation with high oral doses of calcitriol has been communicated. The purpose of this study is to evaluate the effect of this agent on hyperparathyroidism in CAPD patients. Two different groups were constituted according to the length of time on dialysis when HP was detected. All of the patients had i-PTH serum levels five times higher than the normal values (50 pg/ml). During a six month period the daily dose of oral calcitriol was increased in order to achieve a reduction in i-PTH level. The results after this period showed a significant reduction in i-PTH levels (614 +/- 378 to 241 +/- 80 pg/ml) with an average increase in oral calcitriol from 0.16 +/- 0.1 to 0.67 +/- 0.4 with no significant changes in serum calcium or phosphorus. The group with HP at start of dialysis achieved these effects easier and with lower doses of calcitriol. We conclude that moderately high doses of oral calcitriol control secondary hyperparathyroidism in CAPD patients without hypercalcemia.
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PMID:Secondary hyperparathyroidism in CAPD patients: its suppressibility with high doses of calcitriol. 198 16

We describe the case of a 42-year-old woman diagnosed of chronic renal failure secondary to sarcoidosis. Since the beginning of the dialysis treatment she presented episodes of symptomatic hypercalcemia which did not response to calcium restriction diet and a lower calcium concentration in the dialysate. Secondary hyperparathyroidism and aluminium intoxication were biochemically ruled out. Hypercalcemic crisis were associated to 1.25-dihydroxy-vitamin D (1.25-D) serum levels abnormally raised and they responded quickly to low doses of corticosteroids. Subsequently, this treatment had to be withdrawn because of upper gastrointestinal bleeding, and hypercalcemia recurred. Chloroquine phosphate was prescribed with a rapid response to normalize the serum calcium levels. No side effects was recorded. Twelve months later of chloroquine therapy, the patient remained normocalcemic. A bone biopsy showed an active osteopenia without aluminium deposits, hyperparathyroidism signs or granuloma. We discuss about the pathogenesis of hypercalcemia in this case and its relation with abnormal high serum levels of 1.25-D in hemodialysis patients and sarcoidosis.
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PMID:[Hypercalcemia in a female patient with chronic kidney failure secondary to sarcoidosis: a metabolic study of the calcium metabolism and bone histology]. 205 1

Secondary hyperparathyroidism is common in chronic renal failure and is due to inadequate synthesis of calcitriol, the active metabolite of vitamin D. Intravenous administration of alphacalcidol, a synthetic analogue which is metabolized to calcitriol, was given during 12 weeks to 51 patients on chronic hemodialysis in doses between 1 and 4 micrograms/dialysis session. The treatment caused a modest rise, by 0.25 mmol/l, in serum calcium but a 60% reduction of intact serum PTH concentrations. Most patients acquired normal PTH values and hypercalcemia was easily avoided by dose adjustments. There was a significant reduction in serum PTH within the 1st week before the serum calcium concentrations were increased, but after that time the induced suppression of PTH was correlated to the induced rise in serum calcium. These observations are compatible with the view that calcitriol exerts both a direct inhibition of PTH release and increases the gland's sensitivity to calcium. The major implication of the study is that intravenous treatment with alphacalcidol is of great clinical value since it is easy to administer and provides suppression of hypersecretion of PTH with few side effects.
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PMID:Effects on serum parathyroid hormone of intravenous treatment with alphacalcidol in patients on chronic hemodialysis. 239 90

Secondary hyperparathyroidism is a universal complication of chronic renal failure. It has been proposed that the markedly elevated levels of immunoreactive parathyroid hormone (i-PTH) in uremia may represent a "uremic toxin" responsible for many of the abnormalities of the uremic state. Plasma i-PTH consists of a mixture of intact hormone, a single-chain polypeptide of 84 amino acids, and smaller molecular weight hormonal fragments from both the carboxy- and amino-terminal portion of the PTH molecule. The hormonal fragments arise from metabolism of intact PTH by peripheral organs as well as from secretion of fragments from the parathyroid glands. The structural requirements for the known biological actions of PTH reside in the amino-terminal portion of the PTH molecule. Carboxy-terminal fragments, biologically inactive at least in terms of adenylate cyclase activation, hypercalcemia, or phosphaturia, depend on the kidney for their removal from plasma, and thus accumulate in the circulation in chronic renal failure. It is unknown at the present time if other biological effects of these carboxy-terminal fragments may contribute to some of the biochemical alterations observed in uremia. The most significant consequence of increased PTH levels in uremia is the development of bone disease characterized by osteitis fibrosa. In addition, it would appear that PTH plays an important role in some of the abnormal electroencephalographic patterns observed in uremia. This may be due to a potential role of PTH in increasing calcium content of brain. Parathyroid hormone also has been implicated as a pathogenetic factor in many other alterations present in uremia, i.e., peripheral neuropathy, carbohydrate intolerance, hyperlipidemia, and other alterations. Unfortunately, outstanding clinical research is lacking in this field and conclusive experimental data are practically nonexistent. Further studies are necessary if one is to accept the concept of PTH being a significant "uremic toxin."
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PMID:Parathyroid hormone metabolism and its potential as a uremic toxin. 699 9


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