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)

Maxacalcitol (22-oxacalcitriol [OCT]) is a newly developed vitamin D analogue in Japan. OCT has shown less calcemic action and a strong suppressive effect on parathyroid hormone (PTH) in uremic rats and dogs. In uremic patients with secondary hyperparathyroidism, OCT dose-dependently suppressed PTH secretion and increased serum calcium levels. However, more than 60% of patients achieved a greater than 30% decrease in intact PTH level from baseline with long-term OCT treatment up to 1 year without an unphysiological increase in mean serum calcium levels. Long-term treatment also brought about a reduction in bone metabolic markers, including bone alkaline phosphatase, tartrate-resistant acid phosphatase, and bone gra-protein. These results suggest that although careful attention should be paid to the onset of hypercalcemia and oversuppression of PTH, OCT is one of the effective tools for the treatment of secondary hyperparathyroidism.
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PMID:Clinical effects of maxacalcitol on secondary hyperparathyroidism of uremic patients. 1157 42

Patients with chronic renal failure frequently develop secondary hyperparathyroidism, primarily as a result of phosphate retention and low serum 1,25(OH)2D3. Replacement therapy with calcitriol or its synthetic precursor alfacalcidol [1alpha(OH)D3] often produces hypercalcemia, especially when combined with calcium-based phosphate binders. In addition, the natural vitamin D compounds can exacerbate the hyperphosphatemia in patients with chronic renal failure. This combined increase in calcium and phosphate has been correlated with vascular calcification leading to coronary artery disease, the most common cause of mortality in renal patients. Several vitamin D analogs have now been developed that retain the direct suppressive action of calcitriol on the parathyroid glands but have less calcemic activity, thereby offering a safer and more effective means of controlling secondary hyperparathyroidism. Maxacalcitol [22-oxa-1,25(OH)2D3] and falecalcitriol [1,25(OH)2-26,27-F6-D3] are currently available in Japan, and paricalcitol [19-nor-1,25(OH)2D2] and doxercalciferol [1alpha(OH)D2] are available in the US. The mechanisms by which these analogs exert their selective actions on the parathyroid glands are under investigation. The low calcemic activity of maxacalcitol has been attributed to its rapid clearance from the circulation. This prevents sustained effects on intestinal calcium absorption and bone resorption, but still allows a prolonged suppression of parathyroid hormone gene expression. The selectivity of the other analogs is achieved by distinct mechanisms. Understanding how these compounds exert their selective actions on the parathyroid glands will aid in the design of safer, more effective analogs.
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PMID:Vitamin D analogs: new therapeutic agents for secondary hyperparathyroidism. 1583 85

We have previously suggested that when parathyroid glands progress to nodular hyperplasia, secondary hyperparathyroidism (2HPT) may be refractory to medical treatments, including treatment with Maxacalcitol (OCT). In the present study we evaluated the clinical features and hyperplastic patterns of parathyroid glands in patients who underwent parathyroidectomy (PTx) after being withdrawn from OCT. One hundred and eighty-seven advanced 2HPT patients who had been withdrawn from OCT and required PTx were enrolled. At the start of OCT treatment, the patients had a mean age of 55.3 years and had been receiving hemodialysis (HD) for a mean period of 149 months. At the start of OCT treatment and at PTx, the mean intact PTH (i-PTH) levels were 772.8 +/- 446.0 and 855.5 +/- 420.5 pg/mL, respectively. The main reasons for withdrawal of OCT treatment were persistently high PTH (n = 148), hypercalcemia (n = 79), hyperphosphatemia (n = 65), and progressive symptoms (n = 60). We classified the parathyroid glands by hyperplastic pattern into four categories: diffuse hyperplastic gland (D), early nodularity in diffuse hyperplastic gland (EN), nodular hyperplastic gland (N), and single nodular gland (SN). The mean total excised gland weight was 2592.6 mg. Out of a total of 706 glands, 118 were classified as D, 66 as EN, 436 as N, and 86 as SN. All patients had at least one nodular hyperplastic gland or single nodular gland. The mean number of nodular hyperplastic glands and/or single nodular glands was 2.9. All hemodialysis patients with advanced OCT-refractory 2HPT who underwent PTx had at least one nodular hyperplastic gland or single nodular gland.
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PMID:Clinical features and hyperplastic patterns of parathyroid glands in hemodialysis patients with advanced secondary hyperparathyroidism refractory to maxacalcitol treatment and required parathyroidectomy. 1766 32