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)

Hyperparathyroidism is a disease characterized by hypercalcemia with hypophosphoremia resulting from increased secretion of parathyroid hormone (PTH). The disease may be divided into 3 forms: a) primary, b) secondary, c) tertiary (secondary refractory form). Primary hyperparathyroidism is rare in children; hyperplasia is more frequent during the early years of life (neonates and infants) and is difficult to distinguish from adenoma in children. The disease may be asymptomatic; elevated calcemia levels (>12 <13.5 mg/dl) are accompanied by anorexia, asthenia and persistent stipsis; severely elevated concentrations (>13.5 mg/dl) are accompanied by nausea, vomiting, polyuria due to osmosis, with dehydration and progressive onset of lethargy, stupor and coma. Osteopenia or osteitis fibrosa cystica may be present due to augmented bone resorption. Height and weight increases are altered due to anorexia and dehydration. Differential diagnosis includes iatrogenic causes of hypercalcemia (excessive vitamin D intake, prolonged immobilization, etc.) and idiopathic familial hypercalcemia. Emergency treatment is required in cases of extremely elevated hypercalcemia (Ca >13.5-14 mg/dl), due to risk of injury to the heart, the central nervous system, the gastrointestinal tract and the kidneys. The 4 cardinal points of treatment are: hydration, calciuresis, inhibition of bone calcium resorption, treatment of the cause underlying hyperparathyroidism. Secondary hyperparathyroidism is found in cases where chronic hypocalcemia is present, particularly in chronic renal failure, untreated deficiency rickets, chronic intestinal malabsorption, hepatobiliary disease, types I and II vitamin D-dependent rickets, tubular acidosis or Fanconi's syndrome. The tertiary form is distinguished by the autonomous nature of the parathyroid glands which have become hypertrophic/hyperplastic due to uncontrollable, chronic severe renal failure. It can also be of iatrogenic origin due to excessive intake of inorganic phosphates in familial hypophosphatemic rickets or chronic vitamin D deficiency.
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PMID:Hyperparathyroidism. 1524 24

Secondary hyperparathyroidism (SHPT) is associated with parathyroid gland hyperplasia, increased parathyroid hormone (PTH) production and secretion, disturbed bone and mineral metabolism, soft tissue calcification and an increased risk of death. The condition is an almost universal complication of end-stage renal disease (ESRD) and currently is managed by treatment with phosphate binders and vitamin D compounds, both of which are associated with significant side effects, including hypercalcaemia and hyperphosphataemia. Therapy with calcimimetics is a new approach to the treatment of SHPT. These agents act at the calcium-sensing receptor (CaR), where they increase the sensitivity of the receptor to ionized serum calcium. Activation of the CaR results in a rapid reduction in PTH secretion. The calcimimetic drug cinacalcet HCl currently is undergoing clinical trials in dialysis patients who have uncontrolled SHPT, despite treatment with vitamin D compounds and/or phosphate binders. Clinical trials have confirmed that the drug rapidly reduces plasma PTH, phosphorus and calcium-phosphorus product (Ca x P) levels, and that levels of PTH, phosphorus and Ca x P remain suppressed for up to 3 years. In clinical trials, cinacalcet HCl was a well-tolerated drug; only nausea and vomiting occurred more frequently in patients who took cinacalcet HCl than in those who took placebo, and the occurrence of transient hypocalcaemia was limited to the initial phase of the treatment. Cinacalcet HCl is therefore a potentially highly effective and well-tolerated treatment for SHPT in patients with ESRD.
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PMID:Clinical experience with cinacalcet HCl. 1528 57

Secondary hyperparathyroidism (2HPT), a common disorder in patients with chronic renal failure, develops in response to phosphate retention and low serum 1,25-dihydroxyvitamin D(3) [1,25 (OH) (2)D(3), calcitriol] . Replacement therapy with calcitriol or its precursor 1alpha-hydroxyvitamin D(3) [1alpha (OH) D(3), alfacalcidol] often produces hypercalcemia and hyperphosphatemia in these patients. Several vitamin D analogues have been developed that retain the direct suppressive action of 1,25 (OH) (2)D(3) on the parathyroid glands but have less calcemic activity, therapy offering a safer and more effective means of controlling 2HPT. 1,25-D dihydroxy-19-norvitamin D(2) (19-nor D(2)) and 1alpha-hydroxyvitamin D(2) (1alphaOHD(2)) are available in the United States and 1,25-dihydrox-22-oxavitamin D(3) (22-oxacalcitriol, OCT) and 1,25-dihydroxy-26,26,26,27,27,27-hexafluorovitamin D(3) [1,25 (OH)(2)26,27F(6)D(3), falecalcitriol] have been approved for use in Japan. Animal studies have demonstrated that OCT and 19-nor D(2) have a wider therapeutic window for suppression of parathyroid hormone (PTH) because of their lower calcemic activities of OCT has been attributed to its rapid clearance which prevents sustained effects on intestinal calcium absorption and bone resorption, but still allows a prolonged suppression of PTH gene expression and parathyroid cell growth. The calcemic activity of 19-norD(2) diminishes with the duration of treatment by as yet unknown mechanisms. The lower toxicity of 1alphaOHD(2), compared 1alphaOHD(3). has also been noted with chronic, but not acute administration, perhaps due to differential metabolism. The unique actions of falecalcitriol may also result from altered metabolism. A clear understanding of the molecular basis for the selectivity of vitamin D analogues on parathyroid function may allow the design of even more effective analogues.
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PMID:[Renal failure and vitamin D]. 1577 56

Calciphylaxis is a rare but significant condition. It is associated with a high degree of morbidity and is fatal in between 60% and 80% of patients. It occurs most commonly in patients with endstage renal failure and is associated with hypercalcaemia or hyperphosphataemia or both (elevated calcium-phosphate product). Secondary hyperparathyroidism is also common. Clinically, patients develop rapidly progressive, necrotic skin ulcers that are extremely painful. They, universally, respond poorly to usual ulcer therapies. Some surgeons advocate parathyroidectomy for patients with calciphylaxis. Evidence is inconclusive regarding this treatment; however, some trials have shown improved rates of ulcer healing and overall survival in patients treated with parathyroidectomy.
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PMID:Calciphylaxis and its surgical significance. 1593 51

Secondary hyperparathyroidism is a common complication of end-stage renal disease (ESRD) that is often treated with activated forms of intravenous vitamin D. The natural course and treatment of secondary hyperparathyroidism in hemodialysis patients is punctuated by episodes of hypercalcemia, hyperphosphatemia, and increased calcium-phosphate product, which in previous studies were linked to increased mortality. Historically these episodes have been attributed to vitamin D, leading some authorities to favor decreased vitamin D use. However, the studies that examined the impact of mineral levels and parathyroid hormone (PTH) on survival did not consistently account for vitamin D therapy itself on hemodialysis patient survival. The current review examines in detail two recent large-scale studies of hemodialysis patients: one that demonstrated a survival advantage of paricalcitol over calcitriol and a second that demonstrated a significant survival advantage of any intravenous vitamin D formulation versus none. In both studies, the effects were independent of mineral and PTH levels, suggesting "nontraditional" actions of vitamin D contributed to the observed survival advantage. Several of these nontraditional actions are reviewed with an emphasis on those that might impact hemodialysis outcomes.
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PMID:Beyond minerals and parathyroid hormone: role of active vitamin D in end-stage renal disease. 1607 53

Secondary hyperparathyroidism (SHPT) remains an inevitable consequence of untreated chronic uremia. It is the result of a combination of phosphate (P) retention, failure of calcitriol synthesis, and hypocalcemia. Therapies used to correct these abnormalities, namely active vitamin D replacement, calcium (Ca) supplementation, and phosphate (P) restriction, have moderate efficacy but are prone to unacceptable side-effects. However, there have been new developments in the control of P, vitamin D replacement and modulation of the Ca sensing receptor (CaSR) using calcimimetics. Sevelamer, and in the near future lanthanum, are offering a reasonable level of P control without the toxicities inherent with either aluminum- or Ca-based phosphate binders, and other phosphate binders are in development. 'Non calcemic' vitamin D metabolites include 22-oxacalcitriol, paricalcitol, and doxercalciferol. In various experimental models 22-oxacalcitriol, in particular, exhibits impressive suppression of parathyroid hormone (PTH) with minimal calcemia, although it has been less impressive when compared with calcitriol in controlled studies in hemodialysis (HD) patients. The advantages of these agents over conventional treatment with calcitriol or alfacalcidol remain uncertain. Cinacalcet, a calcimimetic agent that up-regulates the sensitivity of the CaSR in parathyroid and other cells, is a new type of therapy for SHPT that simultaneously reduces the concentrations of PTH, Ca, and P in HD patients, enabling a significant number to achieve K/DOQI or other national guidelines. The extent to which this new therapy will improve clinical outcomes remains uncertain. In conclusion, with the advent of new therapies the emphasis in the management of SHPT has evolved to incorporate reduction of Ca loading, control of PTH within specific target ranges, and avoidance of hypercalcemia, hyperphosphatemia and elevation of the calcium phosphorus product.
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PMID:Management of secondary hyperparathyroidism. 1610 40

Currently, >300,000 patients with end-stage renal disease require dialysis. Secondary hyperparathyroidism is a serious complication of end-stage renal disease and can lead to renal osteodystrophy and other organ failure. Vitamin D sterols and phosphate binders are used to treat hyperparathyroidism, but they can cause hypercalcemia, which contributes to vascular and soft-tissue calcification. Cinacalcet (Sensipar) is the first agent in its class that treats secondary hyperparathyroidism by increasing the sensitivity of calcium sensing receptors. It is also indicated for the treatment of hypercalcemia in patients with parathyroid carcinoma. All clinical trials concluded that cinacalcet is effective for the reduction of parathyroid hormone, serum calcium, phosphorus, and calcium-phosphate product levels. Cinacalcet is available as a once-daily oral therapy. Adverse effects are generally mild.
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PMID:Cinacalcet hydrochloride (Sensipar). 1620 Jan 70

Secondary hyperparathyroidism is sometimes seen in patients with hypophosphatemic osteomalacia after long-term oral phosphate therapy. Parathyroidectomy is sometimes needed for the correction of hypercalcemia in these patients, and is rarely performed in patients without hypercalcemia. A 46-year-old female patient had hypophosphatemic osteomalacia with unknown cause and secondary hyperparathyroidism. A palpable neck mass developed after long-term oral phosphate therapy. An intrathyroid parathyroid gland was confirmed through partial thyroidectomy and parathyroidectomy. Renal phosphate wasting decreased strongly, and serum parathyroid hormone was in the normal range after the operation. A correction of secondary hyperparathyroidism may partially overcome hyperphosphaturia in some patients with hypophosphatemic rickets.
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PMID:Secondary hyperparathyroidism as a palpable intrathyroid parathyroid gland in a patient with hypophosphatemic osteomalacia. 1650 17

Secondary hyperparathyroidism is a common complication of patients with chronic kidney disease. Treatment with calcitriol, the active form of vitamin D, reduces parathyroid hormone levels, but may result in elevations in serum calcium and phosphorus. New vitamin D analogues have been developed to reduce parathyroid hormone secretion without concomitant hypercalcaemia and hyperphosphataemia. Recent data from studies with paricalcitol capsules, the oral formulation of 19-nor-1,25(OH)2D2, show a significant reduction in parathyroid hormone levels with no change in calcium and phosphorus levels when compared with placebo. Paricalcitol also compares favourably to other oral vitamin D analogues, effectively decreasing parathyroid secretion with less hypercalcaemia and hypercalciuria than other agents.
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PMID:Paricalcitol capsules for the control of secondary hyperparathyroidism in chronic kidney disease. 1655 77

Secondary hyperparathyroidism (SHPT) is a common and serious complication of chronic kidney disease (CKD). It affects more than 300,000 end-stage renal disease patients treated by dialysis and probably more than 3 million patients with CKD worldwide. For a long time, traditional therapies for SHPT had consisted of correcting the hypocalcemia using calcium salts and vitamin D derivatives, preventing the hyperphosphatemia by calcium- or aluminum-containing intestinal phosphate binders, and recently by using no metal-containing intestinal phosphate binders; however, these therapies are limited by the occurrence of hypercalcemia, hyperphosphatemia, and the lack of specificity and long-term efficacy. Moreover, surgical parathyroidectomy (PTX), which remains the gold standard therapy, is not exempt from risk. PTX exposes patients to anesthesia risks, presurgical and postsurgical complications, and in many cases a permanent state of hypoparathyroidism. Thus, the medical treatment of SHPT became an ideal target for the development of new therapies and strategies. The purpose of this article is to provide an overview of these new therapies, including vitamin D analogs, intestinal phosphate binders, calcimimetics, parathyroidectomies, tyrosine kinase inhibitors, azydothymidine, anticalcineurins, N-terminal truncated parathyroid hormone fragments, bisphosphonates, calcitonin, osteoprotegerin, and others. The use of these new therapies alone or in combination may help to optimize the future treatment of SHPT in CKD patients.
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PMID:New therapies for uremic secondary hyperparathyroidism. 1656 65


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