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)

Calcitonin (CT) plasma levels and urinary hydroxyproline (OHPr) excretion were studied in twenty-eight patients (eleven males and seventeen females) with primary hyperparathyroidism in order to ascertain the effect of CT secretion on the severity of bone disease. The results show that in primary hyperparathyroidism plasma CT levels are increased in about 50% of patients independent of sex. Plasma CT levels were correlated with serum calcium values in males but not in females. Urinary OHPr excretion values appeared higher in those patients which showed lower CT plasma levels. In this latter group the incidence of undetectable CT plasma values was higher in females. The results suggest that in patients with primary hyperparathyroidism the persistent challenge of CT secreting parafollicular cells due to chronic hypercalcemia, may induce a decrease in their functional reserve, and that the bone involvement may have a greater incidence and more severe course in females, due at least in part, for their inability to increase CT secretion as much as males, due to an intrinsic sex-related lower CT secretory reserve.
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PMID:Calcitonin secretion and bone disease severity in hypercalcaemic hyperparathyroidism. 730 85

Concentrations of the hormones and ions involved in calcium homeostasis were analyzed in simultaneous samples of amniotic fluid and maternal blood obtained from normal pregnant women between 14 weeks' gestation and term. Amniotic fluid total calcium, magnesium, and phosphorus levels fell progressively and markedly despite constant or only declining maternal serum levels. Ionized calcium was constant in both amniotic fluid (mean 2.22 mEq/L) and maternal serum (mean 2.33 mEq/L) throughout gestation. Parathyroid hormone levels in amniotic fluid declined after 20 weeks' gestation, despite rising maternal serum levels, consistent with suppressed fetal parathyroid activity secondary to the relative hypercalcemia of late fetal life. Calcitonin levels in both amniotic fluid and maternal serum were unchanged throughout gestation, with amniotic fluid levels being significantly lower than those in maternal serum.
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PMID:Calcium-regulating hormones and ions in amniotic fluid. 735 41

A case of subcutaneous fat necrosis (SFN) is presented. The infant developed late onset hypercalcaemia of severe degree. Calcitonin failed to normalize the hypercalcaemia. Glucocorticoids and withdrawal of dietary calcium and vitamin D are the treatment of choice. Like hypercalcaemia in association with other granulomatous diseases, SFN is possibly secondary to locally produced 1,25-dihydroxy-cholecalciferol. Our results were not able to confirm this theory. Infants with SFN should have calcium levels monitored closely for months.
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PMID:[Subcutaneous fat necrosis with hypercalcemia]. 748 54

Osteoporosis is the most important metabolic bone disease and places an increasing burden on the healthcare system. The condition can be prevented by the early introduction of hormone replacement therapy. The role of bisphosphonates in achieving the same result is being actively explored. The attraction of preventing bone loss is that it preserves the micro-architecture of bone, and therefore its mechanical integrity. The great problem of treating the established condition is that substantial bone loss is accompanied by architectural disintegration. Replacing lost bone may not necessarily restore mechanical integrity and protect against fractures. The management of Paget's disease has been quite revolutionised by the introduction of the bisphosphonates. The condition is a result of a primary increase in osteoclastic bone resorption which can be corrected by bisphosphonates, with considerable symptomatic improvement. The increasing potency and safety margin of the newer agents has meant that the threshold for treatment has fallen. There is now potential for long term control of bone turnover with the hope of preventing late complications. Hypercalcaemia of malignancy is usually the result of both increased bone destruction and decreased urinary calcium excretion. These two components of hypercalcaemia demand different approaches to management. The general availability of an ever-expanding range of increasingly potent bisphosphonates has resulted in a dramatic improvement in the treatment of increased bone resorption associated with malignancy. Many types of tumour, either directly or indirectly, compromise the ability of the kidney to eliminate a calcium load derived from increased bone destruction. Calcitonin is the only agent which is currently available to counter this process.
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PMID:Drugs used in the treatment of metabolic bone disease. Clinical pharmacology and therapeutic use. 750 48

Hypercalcemia of malignancy is most commonly due to the effects of parathyroid hormone-related peptide, which acts as a humoral factor to cause generalized osteoclast-mediated bone resorption and reabsorption of calcium by the kidney tubule, and may also act as a local resorptive factor adjacent to bone metastases. Local resorptive mechanisms are less common causes of malignant hypercalcemia than previously believed. Treatment begins with intravenous fluid rehydration, followed by a furosemide diuresis and the bisphosphonate pamidronate, 60-90 mg, intravenously. Gallium nitrate is an efficacious but inconvenient alternative to pamidronate. Calcitonin combined with pamidronate is a reasonable initial therapy for severe hypercalcemia to hasten normalization of the serum calcium. Steroids should be reserved for hypercalcemia due to tumor production of 1,25 dihydroxyvitamin D, or for steroid-responsive malignancies. Oral or parenteral bisphosphonates can be used to maintain normocalcemia. In addition to improving the morbidity of acute hypercalcemia, bisphosphonate therapy has been shown to reduce bone pain and pathological fractures in patients with bone metastases, and calcitonin also has a potent analgesic effect in these patients. Treatment for hypercalcemia should therefore be considered in the majority of patients in the palliative care setting.
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PMID:Hypercalcemia of malignancy in the palliative care patient: a treatment strategy. 754 27

Calcitonin-secreting cells, 'C cells', have specific receptors for calcitriol, thus the calcitriol deficiency in uraemia may affect calcitonin secretion and/or production. The aim of the present study was to evaluate in CAPD patients the effect of calcitriol replacement (4 weeks of oral calcitriol, 0.5 micrograms/day) on both, basal calcitonin concentration and calcitonin response to calcium infusion (calcium gluconate, 3 mg/kg/h). Calcitriol replacement produced a normalization of serum calcitriol level without a significant change in serum calcium concentration. After calcitriol replacement, basal calcitonin increased from 78 +/- 15 to 101 +/- 13 pg/ml, P < 0.05. The increment in calcitonin induced by a calcium infusion was lower after (15 +/- 4 pg/ml) than before (29 +/- 4 pg/ml) calcitriol replacement. In addition, calcitriol administration induced a decrease in serum PTH level. Replacement of calcitriol in CAPD patients produced an increase in serum calcitonin concentration and a decrease in the calcitonin response to hypercalcaemia.
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PMID:Effect of calcitriol replacement on serum calcitonin and parathyroid hormone levels in CAPD patients. 772 33

We studied four children with hypercalcemia of immobilization resulting from quadriplegia. After a trial of conventional therapy, human synthetic calcitonin was given subcutaneously at 0.5 to 2.5 mg per day in divided doses. Serum calcium concentrations returned to normal levels in all patients, decreasing an average of 0.72 mmol/L (2.9 mg/dl) within 4 to 10 days. Calcitonin therapy was effective for periods varying from 3 to 10 months. In one patient a bladder stone developed without nephrocalcinosis.
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PMID:Human synthetic calcitonin therapy for hypercalcemia of immobilization. 775 17

Calcitonin inhibits both osteoclast formation and bone resorption, and is a primary treatment for patients with hypercalcemia and increased bone turnover. However, the clinical utility of calcitonin is limited because patients become refractory to calcitonin after several days (the calcitonin "escape phenomenon"). The molecular basis for calcitonin "escape" is unclear. To determine the regulatory mechanisms controlling calcitonin receptor (CTR) expression in osteoclasts and their precursors, we treated immature mononuclear precursors for human osteoclast-like multinucleated cells (MNC) formed in vitro with 1,25-(OH)2D3, to induce their differentiation to committed mononuclear precursors, and mature multinucleated osteoclasts, and used reverse transcriptase (RT)-PCR to assess expression of CTR mRNA in both committed mononuclear precursors and MNC. The PCR fragment produced was cloned and sequenced to confirm that it was derived from CTR mRNA. CTR mRNA expression was detected in mononuclear MNC precursors after 7 d of 1,25-(OH)2D3 treatment. It was also present in osteoclast-like MNC and highly purified giant cells from osteoclastomas, but not in monocytes or macrophage polykaryons formed in vitro. Calcitonin markedly decreased CTR but not actin mRNA expression in giant cells and MNC after 12 h, and removal of calcitonin restored CTR mRNA expression. Similarly, calcitonin decreased calcitonin-induced adenylate cyclase activity. These data suggest: (a) downregulation of CTR gene expression by calcitonin may in part explain the calcitonin "escape phenomenon"; and (b) expression of CTR mRNA occurs in mononuclear osteoclast precursors within 7 d after exposure to 1,25-(OH)2D3.
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PMID:Downregulation of calcitonin receptor mRNA expression by calcitonin during human osteoclast-like cell differentiation. 781 11

24-Hydroxylase is found in many mammalian tissues and is required as an initial step in the deactivation of vitamin D3 metabolites and most of its active analogs. We studied the regulation of intestinal 24-hydroxylase (I-24-OHase) activity and messenger RNA (mRNA) expression in rats as influenced by calcium and vitamin D status. Rats were fed vitamin D-replete diets containing either normal calcium (1.0-1.2%, designated NC) or low calcium (0.02%; designated LC). Half of the NC and LC rats received 25,000 IU vitamin D3 three times weekly, orally, and were designated NCT and LCT, respectively. We found that I-24-OHase mRNA expression was up-regulated in rats receiving excess vitamin D3 (NCT and LCT). We observed, however, that the up-regulation was much more dramatic in the LCT group and exceeded by 4.5-fold that observed in the NCT group. Plasma calcium was also elevated in the NCT group (12.6 +/- 0.2 mg/dl), but not the LCT group (10.5 +/- 0.15 mg/dl). We, therefore, examined the possibility that calcitonin released in response to hypercalcemia may have suppressed the induced expression of I-24-OHase mRNA in the NCT group. The plasma calcitonin level was higher in the NCT group (36.14 +/- 2.46 pg/ml) relative to that in the LCT group (19.38 +/- 2.28 pg/ml). Thyroparathyroidectomy also resulted in a 2-fold (P < 0.001) increase in I-24-OHase activity in the NCT group, a response that was reversed (within 4 h) with a single dose of calcitonin (100 IU/rat). Calcitonin administration to LCT rats also resulted in a significant (P < 0.001) 5-fold reduction in I-24-OHase mRNA expression. These data suggest that calcitonin is a potent negative regulator of I-24-OHase mRNA expression and I-24-OHase activity and that the release of calcitonin may block an important pathway for the inactivation of vitamin D3 metabolites in intestine and, thereby, potentiate the toxicity of vitamin D3 during periods of its excess consumption.
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PMID:In vivo regulation of rat intestinal 24-hydroxylase: potential new role of calcitonin. 795 16

Long-term corticosteroid therapy is the most frequent and most severe cause of iatrogenic osteoporosis. Hypocalcaemia, subsequent to the induced negative calcium balance, may lead to secondary hyperparathyroidism. Corticosteroids also affect bone itself, probably by disrupting the production of growth factors. Bone resorption increases and bone formation decreases leading to a reduction in total bone mass. The relative immobilization resulting from the corticoid-induced myopathy or the underlying disease may accelerate the process. On the average, after one year of treatment, 5% of the bone mass is lost, and loss may reach as much as 10 to 30% at certain sites. Nearly 40% of all subjects on long-term corticosteroids suffer fractures. Other iatrogenic causes include anticonvulants which perturb phosphocalcium metabolism, 1-thyroxin which leads to bone loss when administered for hormone substitution, gonadotropin-releasing hormone antagonists which inhibit the hypophyseal-ovarian axis, tamoxifen (used in the treatment of breast cancer) which has an oestrogen-like effect, and other circumstances such as chemotherapy and long-term heparin. The gravity of iatrogenic osteroporosis thus requires preventive measures. Calcium and vitamin D supplements can compensate for impaired intestinal absorption of calcium but have no effect on bone density. One-alpha hydroxyl derivatives have been suggested but their effect remains controversial. Calcitriol can prevent bone loss in the lumbar vertebrae but hypercalcaemia occurs in one-fourth of the cases, limiting its use. Recent reports have shown that anti-oestroclastic agents may be useful. Nandrolone decaonate would have a favourable effect on bone loss but also causes virilization. In patent osteoporosis, fluorine can be combined with calcium resulting in increased lumbar bone density. Calcitonin and calcium can also be combined to induce a rise in bone density. The long-term effects of these treatments in terms of reduced fracture risk remain to be determined. A better understanding of the adverse effects of the different classes of corticosteroids is essential for optimal treatment. In cases requiring long-term therapy implicating the risk of iatrogenic osteoporosis, bone density quantitation can be a valuable means of evaluating bone loss, and of adapting preventive or corrective measures.
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PMID:[Iatrogenic demineralizing osteopathies]. 820 75


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