Calcitonin Hypocalcemia

Other Calcium Disorders. In addition to hypocalcemia, tremors, osteoporosis, and muscle spasms (tetary), calcium deficiency can lead to rickets, osteomalacia, and possibly heart disease. These, as well as Paget s disease, can also result from faulty utilization of calcium. Calcium excess can lead to excess secretion of calcitonin, possible calcification of soft tissues, and kidney stones when combined with magnesium deficiency. 

Hypocalcemia directly increases PTH synthesis and release and inhibits calcitonin release. PTH in turn restores plasma calcium by initially stimulating transport of free or labile calcium from bone into the blood. PTH also increases renal 1,25-dihydroxycholecalciferol (1,25-(0H)2D3) production, which is the most active form of D3. 1,25-(0H)2D3 induces enterocyte differentiation in the intestine, which in turn results in increased absorption of calcium. Finally, during long periods of hypocalcemia, PTH can mobilize more stable calcium deep in the hydroxyapatite of bone by activating deep osteoclasts. 

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. 

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... 

The main features of hypocalcemia are neuromuscular—tetany, paresthesias, laryngospasm, muscle cramps, and convulsions. The major causes of hypocalcemia in the adult are hypoparathyroidism, vitamin D deficiency, chronic kidney disease, and malabsorption. Neonatal hypocalcemia is a common disorder that usually resolves without therapy. The roles of PTH, vitamin D, and calcitonin in the neonatal syndrome are under active investigation. Large infusions of citrated blood can produce hypocalcemia by the formation of citrate-calcium complexes. Calcium and vitamin D (or its metabolites) form the mainstay of treatment of hypocalcemia. 

Calcitonin causes the deposition of calicum phosphate in the skeleton by stimulation of the bone-forming cells, and hence reduces the levels of calcium and phosphate in the blood (hypocalcemia). Completely synthetic calcitonin products such as Salmcalci-tonin (Sandoz Ltd., Switzerland) 208), Elcitonin (Toyo Jozo Co., Japan) z09), and... 

In hypocalcemia, the parathyroid increases its secretion of parathormone, resulting in enhanced liberation of Ca2+. Calcitonin transfers active osteoclasts into a resting state. Calcitonin given therapeutically relieves pain associated with neoplastic bone metastases and vertebral body collapse. Estrogens diminish bone resorption by (a) inhibiting activation of osteoclasts by osteoblasts and (b) promoting apoptosis of osteoclasts. 

Calcitonin (ihyrocalcilonin) is a 32-amino-acid polypeptide hormone secreted by parafollicular cells of the thyroid glands in response lo hypocalcemia. The entire 32-residue peplide appears to be required for activity, bccau.se smaller fragments are totally inactive. Common structural features of calcitonin isolated fntm different species are a COOH-lerminal prolinamide. a disulfide bond between residues I... 

The known effects of thyrocalcitonin are primarily in bone. Removal of the gut had no effect on the hypocalcemic effect of calcitonin (A6), and neither did nephrectomy (H8). No change in soft tissue calcium content was seen in soft tissues to explain the hypocalcemia (Kl). Calcitonin apparently inhibits bone resorption and thereby decreases calcium entry into the blood. Calcitonin prevents the release of calcium from cultured bone (A5, FIO). In vivo, the release of Ca from prelabeled bone is decreased by calcitonin (Jl). The bone arteriovenous difference in calcium levels is increased by calcitonin (M3). The mode of action of calcitonin is unknown. Calcitonin does not inhibit parathormone (A6, H7, T3), nor is its effect apparently mediated through RNA synthesis (T3). 

The thyroid gland also synthesizes calcitonin, which produces hypocalcemia by inhibiting bone resorption and by enhancing the urinary excretion of calcium and phosphate. 

Example compounds causing hypocalcemia include calcitonin, diuretics, anticonvulsants, fluoride, and ethylene glycol chelating agents—EDTA, metabolites of ethylene glycol... 

Calcitonin is secreted continuously under conditions of normocalcemia, and the synthesis of calcitonin is increased when the calcium concentrations in plasma and intracellular fluids increase. Hypermagnesemia has a similar effect on calcitonin production. In hypocalcemia, the production of calcitonin falls. The gastrointestinal hormones—gastrin, glucagon, cholecystokinin, and secretin—and high dietary calcium also stimulate calcitonin production. Long-term hypercalcemia may cause hyperplasia of the C cells. 

Arnaud (7) has developed a butterfly model that provides a diagrammatic view of the complex interrelationships among the three hormones (parathyroid, calcitonin, and vitamin D) that control calcium homeostasis (serum concentrations of ionic calcium) and their target organs (bone, kidney, and intestine) (Fig. 35.1). The right side (B loops) of the butterfly model describes the processes that increase the serum calcium concentration in response to hypocalcemia the left side (A loops) depicts the events that occur in response to hypercalcemia. 

Hypocalcemia can be caused by PTH deficiency, vitamin D deficiency, various pharmacological agents, and miscellaneous disorders (Table 35.5) (18). A state of hypocalcemia will inhibit calcitonin release. This results in an elevation of PTH biosynthesis and release and indirectly causes an increase in the production of vitamin D. The left wing of Arnaud s butterfly model (Fig. 35.1) would be activated to increase serum calcium concentrations. In the absence of calcitonin, osteoclast activity is unregulated therefore, bone resorption is accelerated. In acute cases of hypocalcemia, specifically in the case of hypocalcemic tetany, PTH is administered to correct the hormonal imbalance. 

The infusion of calcitonin to rats induces increased calcium deposition in the bone and hypocalcemia. Thus, the hormone has properties antagonistic to those of parathormone. Fluorescent antibody techniques have demonstrated that the hormone is secreted by the C cells of the thyroid gland. A light cell hyperplasia outside the follicular walls of the thyroid has been observed in mice with hereditary hypocalcemia. 

Calcitonin is active in nephrectomized and parathy-roidectomized animals, indicating that the hormone does not act through the kidney or the parathyroid. Thyrocalcitonin causes hypocalcemia even in rats fed a low-calcium diet. Consequently, the hormone does riot seem to influence intestinal absorption of calcium. Calcitonin facilitates calcium retention in bone cultures. It is likely that the hormone acts by interfering with calcium resorption in bone, but the exact mechanism by which the interference takes place is not known. 

Calcitonin - Remarkable progress has been made in the last two yesurs in the chemistry and biology of the hypocalcemia horitme calcitonin (CT, thyro-oalcltonin). Several reviews have appeared. 33 hg amino acid... 

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