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Calcium: II Calcitonin


Calcium: II Calcitonin
Clinical background
Medullary thyroid cancer (MTC) is a rare malignancy arising from the parafollicular thyroid C cells that secrete calcitonin. It usually presents as a lump in the thyroid gland or as lymph node metastases in the neck. Diagnosis is made by a biopsy and the treatment is surgical, possibly with adjunctive chemother- apy. MTC may be sporadic or familial and in both types may be associated with phaeochromocytoma or other features of the Multiple Endocrine Neoplasia Type 2 (MEN 2) syndrome (Table 50.1). It is important to distinguish the truly sporadic cases from the first presentation of familial disease as screening can allow early detection and treatment in family members.

Calcitonin, Biosynthesis and secretion, Physiological actions of calcitonin

Calcitonin
Calcitonin is a hypocalcaemic polypeptide hormone. In mammals, it is synthesized and secreted in parafollicular (C) cells in the thyroid gland. C cells have been found in much lower density in the parathyroid glands and in the thymus. In fish and birds, calcitonin is synthesized within a specific organ, the ultimobranchial body. The ultimobranchial bodies do develop in mammals during fetal life, but eventually disappear. It is thought that the C cells evolved before the parathyroids, to help sea-dwelling animals to cope with the relatively high concentrations of calcium in sea water.
Biosynthesis and secretion. The calcitonin gene occurs on the short arm of chromosome 11. Calcitonin (CT) is synthesized in C (clear) cells from a larger 136 amino acid precursor, called calcitonin precursor, from which CT is cleaved, together with two other peptides of unknown function (Fig. 50a). The gene which encodes CT has been characterized, and is expressed not only in the C cells of the thyroid but also in the brain. In neural tissue, however, the gene expresses not CT but another peptide, the calcitonin gene-related peptide (CGRP). This is therefore an example of tissue-determining expression of a common gene.
At normal plasma calcium levels, CT release is low but a rise in calcium causes a rapid (threefold) rise in CT concentrations.
Even if a small amount of calcium, which is insufficient to raise plasma concentrations of the ion in plasma, reaches the gastrointestinal tract (GIT), CT is released. It is therefore thought that other GIT factors, for example gastrin and/or cholecystokinin (CCK), may trigger CT secretion. The sensitivity of the CT-release mechanism is sexually differentiated, being greater in males, and the responsiveness of the CT release mechanism declines with ageing. The half-life of CT in plasma is less than 15 minutes, and it may be degraded and excreted principally by the kidney.
Physiological actions of calcitonin (Fig. 50b). In humans, calcitonin is not as important as is PTH in the regulation of calcium metabolism. The two main target organs for CT are bone and kidney. In bone, CT is a potent inhibitor of resorption, both in vivo and in vitro, although CT has no effects on bone formation. There is an inhibition of calcium resorption by the osteoclasts within 20 minutes of administration of a dose of CT. CT may be particularly important during periods of threatened increased calcium loss, such as occurs during pregnancy and lactation.
In the kidney, CT is concentrated in the renal cortex. Membranes of the tubule cells possess specific CT receptors, and the second messenger may be adenylate cyclase, although administration of CT does not appear to alter cellular levels of cAMP. In the kidney, CT increases the excretion of calcium, sodium and potassium and reduces excretion of magnesium.
CT may be important in the regulation of postprandial feeding, to prevent food-induced hypercalcaemia. CT may also be a satiety hormone. In humans, injection of CT is followed by a significant fall in body weight within 36 hours, and CT inhibits feeding behaviour in rhesus monkeys and rats. The hormone is particularly potent when administered directly to the brain, suggesting that it may have a central role.
CT affects vitamin D metabolism by lowering plasma calcium, resulting in the release of PTH, which in turn promotes the production and secretion of vitamin D metabolites in the kidney.

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