Hypercalcemia calcitonin

The goal of treatment is to reduce bone pain and stabilize or prevent other problems such as progressive deformity, hearing loss, high-output cardiac failure, and immobilization hypercalcemia. Calcitonin and bisphosphonates are the first-line agents for this disease. Treatment failures may respond to plicamycin. Calcitonin is administered subcutaneously or intramuscularly in doses of 50-100 MRC (Medical Research Council) units every day or every other day. Nasal inhalation at 200-400 units per day is also effective. Higher or more frequent doses have been advocated when this initial regimen is ineffective. Improvement in bone pain and reduction in serum alkaline phosphatase and urine hydroxyproline levels require weeks to months. Often a patient who responds well initially loses the response to calcitonin. This refractoriness is not correlated with the development of antibodies. 

The authors suggested that this was the first report of exogenous calcitonin causing hypercalcemia. There were several unknowns in this case, including the calcium concentration before treatment and the concentration of PTHrp, which would have helped to determine the cause of the hypercalcemia. Calcitonin is usually associated with a reduction in calcium concentration rather than a rise. The authors postulated that calcitonin could alter PTHrp concentrations, with different effects depending on cell type. They also provided evidence of hypercalcemia caused by calcitonin in non-human models (14). 

Hypercalcemia of malignancy Many forms of cancer accelerate bone resorption, leading to hypercalcemia Calcitonin, bisphosphonates... 

Calcitonin is secreted when abnormally high calcium levels occur in plasma. Although plasma concentrations are normally minute (<100 pg/mL), they increase two- to threefold after calcium infusion. Calcitonin has a short plasma half-life (ca 10 min). Certain thyroid tumors are the result of CT concentrations 50—500 times normal. The mechanism of action is a direct inhibition of bone resorption. Calcitonin is used clinically in various diseases in which hypercalcemia is present, eg, Paget s disease (46). 

Vitamin D withdrawal is an obvious treatment for D toxicity (219). However, because of the 5—7 d half-life of plasma vitamin D and 20—30 d half-life of 25-hydroxy vitamin D, it may not be immediately successful. A prompt reduction in dietary calcium is also indicated to reduce hypercalcemia. Sodium phytate can aid in reducing intestinal calcium transport. Calcitonin glucagon and glucocorticoid therapy have also been reported to reduce semm calcium resulting from D intoxication (210). 

The answer is c. (Hardman, p 15230 Administration of intravenous CaG would immediately correct the tetany that might occur in a patient in whom a thyroidectomy was recently performed. Parathyroid hormone would act more slowly but could be given for its future stabilizing effect. Long-term control of a patient after a thyroidectomy can be obtained with vitamin D and dietary therapy Calcitonin is a hypocalcemic antagonist of parathyroid hormone. Plicamycin (mithramycin) is used to treat Paget s disease and hypercalcemia. The dose employed is about one-tenth the amount used for plicamycin s cytotoxic action. 

Hypercalcemic crisis and symptomatic hypercalcemia are medical emergencies requiring immediate treatment. Rehydration with normal saline followed by loop diuretics can be used in patients with normal to moderately impaired renal function. Initiate treatment with calcitonin in patients in whom saline hydration is contraindicated (Table 78-3). 

The polypeptide calcitonin is secreted by thyroid C-cells during imminent hypercalcemia. It lowers plasma Ca + levels by inhibiting osteoclast activity. Its uses include hypercalcemia and osteoporosis. Remarkably, calcitonin injection may produce a sustained analgesic effect that is not restricted to bone pain. 

Hypercalcemia can be treated by (1) administering 0.9% NaCl solution plus furosemide (if necessary) renal excretion (2) the osteoclast inhibitors calcitonin, plicamycin, or clodro-nate (a bisphosphonate) bone calcium mobilization i (3) the Ca +chelators EDTA sodium or sodium citrate as well as (4) glucocorticoids. 

Hypercalcemia, in contrast, results in calcitonin synthesis and release, while PTH release and formation of 1,25-(0H)2D2 are inhibited. Calcitonin inhibits bone resorption directly by reducing osteocyte activity. Calcitonin also induces an initial phosphate diuresis, followed by increased renal calcium, sodium, and phosphate excretion. 

Calcitonin release is normally stimulated by rising serum calcium levels and suppressed by hypocalcemia. The major physiological effects of calcitonin are inhibition of bone resorption and deposition of postabsorp-tive calcium into bone following a meal, which prevents postprandial hypercalcemia. 

Calcitonin is also effective in reducing serum calcium levels in life-threatening hypercalcemia however, it is not as rapid or as effective as the bisphosphonates. Subcutaneous administration of salmon (Calcimar) or human (Cibacalcin) calcitonin reduces serum calcium levels within 3 to 5 days in 75 to 90% of malignant hypercalcemias. 

Calcitonin—Paget s disease and hypercalcemia Estrogens Glucocorticoids Biphosphonates—postmenopausal osteoporosis Eluoride... 

Calcium play vital role in excitation - contraction coupling in myocardium. Calcium mediates contraction in vascular and other smooth muscles. Calcium is required for exocytosis and also involved in neurotransmitters release. Calcium also help in maintaining integrity of mucosal membranes and mediating cell adhesions. Hypercalcemia may occur in hyperthyroidism, vitamin D intoxication and renal insufficiency, which can be treated by administration of calcitonin, edetate sodium, oral phosphate etc. Hypocalcemia may occur in hypothyroidism, malabsorption, osteomalacia secondary to leak of vitamin D or vitamin D resistance, pancreatitis and renal failure. Hypocalcemia can be treated by chloride, gluconate, gluceptate, lactate and carbonate salts of calcium. 

Giving intravenous phosphate is probably the fastest and surest way to reduce serum calcium, but it is a hazardous procedure if not done properly. Intravenous phosphate should be used only after other methods of treatment (bisphosphonates, calcitonin, and saline diuresis) have failed to control symptomatic hypercalcemia. Phosphate must be given slowly (50 mmol or 1.5 g elemental phosphorus over 6-8 hours) and the patient switched to oral phosphate (1-2 g/d elemental phosphorus, as one of the salts indicated below) as soon as symptoms of hypercalcemia have cleared. The risks of intravenous phosphate therapy include sudden hypocalcemia, ectopic calcification, acute renal failure, and... 

Teriparatide These hormones act on their cognate receptors coupled to G protein signaling pathways Teriparatide stimulates bone turnover, calcitonin suppresses bone resorption Both are used in osteoporosis calcitonin is used for hypercalcemia Teriparatide may cause hypercalcemia and hypercalciuria... 

A 46-year-old woman with low back pain and osteoporosis took salmon calcitonin subcutaneously 100 U/ day and calcium carbonate orally 1.5 g/day for 7 days before developing nausea and facial flushing (13). Calcitonin was continued for a further 8 days and then stopped. The next day she developed intermittent generalized convulsions. She was subsequently found to have breast cancer with skeletal metastases and hypercalcemia (3.9 mmol/1) without a reduced... 

Calcitonin derived from synthetic sources can be administered to mimic the effects of the endogenous hormone. As described previously, endogenous calcitonin decreases blood calcium levels and promotes bone mineralization. Consequently, synthetically derived calcitonin is used to treat hypercalcemia and to... 

Calcitonin Calcitonin is secreted hy the C cells ofthe thyroid gland in response to hypercalcemia. Its primary action is to oppose the actions of parathyroid hormone hy suppressing osteoclast actions. It also stimulates... 

Calcitonin inhibits osteoclastic bone resorption, increases the urinary excretion of calcium and phosphate, and reduces serum calcium. It is established in the treatment of disorders of high bone turnover, including Paget s disease and postmenopausal osteoporosis, but is less effective than the bisphosphonates. Calcitonin is less effective than other therapeutic measures in the treatment of acute hypercalcemia. Long-term administration of calcitonin reduces morbidity in cases of osteogenesis imperfecta... 

Although antitumor activity was found for gallium nitrate in pha.se II clinical trials. " its approved use is for the treatment of cancer-related hypercalcemia." It has proved superior to calcitonin and etidronate in this use. The clinical material is the nonahydratc of Ga(NOt)t. 

The potential therapeutic uses of calcitonin arc in the treatment of hyperparathyroidism, osteoporosis and other bone-disorders. hypercalcemia of malignancy, and idiopathic hypercalcemia. 

Therapies are directed toward treating the malignancy, decreasing the serum calcium concentration by saline diuresis, and decreasing osteoclastic resorption (bisphos-phonates, calcitonin, etc.). Steroids are useful in reducing intestinal absorption of calcium in l,25(OH)2D-mediated hypercalcemia. 

PTH and 1,25-dibydroxyvitamin D are the primary hormones regulating bone and mineral metabolism. Calcitonin has pharmacological actions, but a physiological role has not been established in adults. PTHrP is the principal mediator of hmnoral hypercalcemia of malignancy. 

Elevated concentrations of calcitonin or increased responsiveness to stimulation have also been reported in acute and chronic renal failure, hypercalcemia, hypergastrinemia and other gastrointestinal disorders, pulmonary disease, and severe iUness. ... 

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