A Clinical Appraisal of Calcitonin

A CLINICAL APPRAISAL OF CALCITONIN T H E account of the results of calcitonin therapyin a group of osteoporotic patients described by Dr Brown and her colleagues on page 207 of this issue of the Scottish Medical Journal provides a stimulus to review the current standing of this newly identified hormone in the clinical scene. In the 8 years since the first announcement by Copp of a hypocalcaemic principle elaborated by the thyro-parathyroid complex of the dog, considerable strides have been made in elucidating the chemical, biochemical, physiological and immunological properties of this hormone. The initial controversy regarding its principal source, whether thyroid or parathyroid, has been resolved in most mammals in favour of the former though subsequent investigation of calcitonin producing 'C' cells (Pearse & Carvalheira, 1967) have shown their actual origin to be from the ultimobranchial body, a hitherto distant embryological memory in the minds of most clinicians, and a group of cells whose ultimate anatomical location varies in different species. In man, 'C' cells are present though difficult to demonstrate in most adult thyroids and their usual situation in the postero-medial portion of the gland makes their identification in the average surgical specimen less likely. It seems probable that calcitonin isalso present in human parathyroid and thymus (Galante et al., 1968) though 'C' cells have yet to be convincingly demonstrated in these tissues. The stimulus to the production and release of the hormone from the 'C' cells is hypercalcaemia and its principal action is to inhibit the resorption of bone (Martin et al., 1966). This activity is much more marked in the young animal-the overall magnitude of the effect being related to the bone turnover rate. When this is high and therefore making a significant contribution to plasma calcium levels hypocalcaemia may ensue. The hormone also reduces the renal tubular reabsorption of calcium (Cochrane et al., 1969). The biochemical rationale of these effects has not yet been defined but they may result from an inhibition of the calcium pump which extrudes calcium from the cell. The effect is not due to a direct inhibition of parathyroid hormone. Chemically, calcitonin is a polypeptide of molecular weight around 3,400 and despite a considerable degree of biological crossreactivity among calcitonins prepared from different species there are marked species differences in the amino acid composition. For example eighteen amino acids out of the thirty two are different in the porcine and human hormone. Such is the pace of protein chemistry today that laboratory synthesis has already been achieved and synthetic human calcitonin is now becoming available. Normal plasma levels can be detected by bioassay techniques after preliminary extraction, and by radioimmunoassay. With the discovery of a new hormone the clinician is prompted to look for syndromes which can be explained in terms of its excess or deficiency and also for clinical situations where a knowledge of its physiological properties encourage the hope of some therapeutic gain. The outstanding clinical condition in which hypercalcitonism is found is medullary carcinoma of the thyroid and it is conceptually interesting that this correlation was discovered (Cunliffe et al., 1968) as a result of histopathological studies suggesting that this tumour may be derived from 'C' cells rather than from a pertinent metabolic upset in this disease. Certainly thyroid tissue and plasma calcitonin levels in medullary carcinoma are usually very high but symptoms due to this excess are very rare and a normal plasma calcium is the rule. It is of interest that there is an association of phaeochromocytoma and Cushing's syndrome with this tumour while the most common extra thyroidal symptom namely diarrhoea is probably related to prostaglandins (Williams et al., 1968) and certainly not to calcitonin. In retrospect the reason for the disappointingly normal routine parameters of calcium metabolism is not difficult to seek since it is now generally believed that in most situations hormonal effects on gut and kidney are more