131LEADING ARTICLES

A New Endocrine Gland

THE LANCETLONDON 20 JANUARY 1968

THE existence of a calcium-lowering hormone, cal-citonin, was first proposed by Copp and others 1 in1962, and thereafter progress was very rapid. After con-firming the existence of the hormone MACINTYRE andhis colleagues at the Royal Postgraduate Medical Schoolwent on to show that it came from the mammalian thy-roid,3 rather than the parathyroid, as Copp had sug-gested. Later work confirmed this view and it is now

widely accepted that calcitonin is identical with the

principle (thyrocalcitonin) 4-7 first noted in crudeextracts of rat thyroid by HIRSCH et al.8 Therefore, theshorter original name seems preferable.The progress of purification of calcitonin has lately

been reviewed.9 9 The porcine hormone has beenobtained in highly purified form by several laboratories :it is a polypeptide with a molecular weight of about 3600.The pure material is extremely active: less than 0-05 I-Lg.produces a maximum hypocalcaemic response in the rat,equivalent to a potency of 200-300 M.R.C. units per mg.The acute action of calcitonin has been thoroughlystudied in animals and is well understood. 10-13Calcitoninlowers plasma-calcium levels by blocking the transfer ofcalcium from bone to blood. Plasma-calcium thereforefalls owing to continued loss of calcium from plasma tobone. This action raised the hope that the hormonemight be an effective treatment for osteoporosis; but,although it has been shown that calcitonin acts on theskeleton in this condition, only lengthy clinical trials willshow whether this action is beneficial.The importance of calcitonin as a hormone in

man 14 15 and its position in human disease are still

uncertain, because a method of immunoassay for plasma-calcitonin has not yet been devised. FOSTER et al.,16however, found that when rats were given calcitonin for28 days the tail vertebrae showed radiological changes1. Copp, D. H., Cameron, E. C., Cheney, B. A., Davidson, A. F. G.,

Henze, K. G. Endocrinology, 1962, 70, 638.2. Kumar, M. A., Foster, G. V., MacIntyre, I. Lancet, 1963, ii, 480.3. Foster, G. V., Baghdiantz, A., Kumar, M. A., Slack, E., Soliman, H. A.,

MacIntyre, I. Nature, Lond. 1964, 202, 1303.4. Lancet, 1966, i, 138.5. Copp, D. H. Am. J. Med. 1967, 43, 648.6. Can. med. Ass. J. 1967, 97, 976.7. Pechet, M. M. Am. J. Med. 1967, 43, 645.8. Hirsch, P. F., Gauthier, G. F., Munson, P. L. Endocrinology, 1963,

73, 244.9. MacIntyre, I. Calc. Tiss. Res. 1967, 1, 173.

10. Hirsch, P. F., Voelkel, E. F., Munson, P. L. Science, N.Y., 1964, 146,412.

11. Gudmundsson, T. V., MacIntyre, I., Soliman, H. A. Proc. R. Soc. B,1966, 164, 460.

12. Robinson, C. J., Martin, T. J., Matthews, E. W., MacIntyre, I.

J. Endocr. 1967, 39, 71.13. Anast, C., Arnaud, C. D., Rasmussen, H., Tenenhouse, A. J. clin.

Invest. 1967, 46, 57.14. Munson, P. L. Ann. intern. Med. 1966, 64, 1353.15. Munson, P. L., Hirsch, P. F. Clin. Orthoped. 1966, 49, 209.16. Foster, G. V., Doyle, F. H., Bordier, P., Matrajt, H. Lancet, 1966, ii,

1428.

reminiscent of the " rugger-jersey spine" sometimesseen clinically in renal osteodystrophy, osteopetrosis,and hyperparathyroidism; so these appearances mightbe human counterparts of the animal experiments.

Progress has also been rapid in the study of the cellssecreting the hormone. PEARSE et a1Y-19 showed thatthe thyroid parafollicular or C cells were the source,and that, in the rodent, these cells had migrated to thethyroid from the ultimobranchial region.2o This hinderpart of the pharyngeal entoderm gives rise to the ulti-mobranchial bodies, which are gland-like structures ofunknown function in the neck or mediastinum of fish,amphibians, reptiles, and birds.But the comparative animal studies have produced

the most exciting developments. On p. 108 ProfessorMACINTYRE and his colleagues provide evidence whichsettles a controversy which has continued since thework of MAURER 21 in 1888. MACINTYRE extracted and

purified calcitonin from the ultimobranchial bodies oflizards, pigeons, and chickens, showing that these struc-tures are really unrecognised endocrine glands, whichconfirms the findings of Copp 22 and TAUBER 23 in thechicken. Calcitonin is therefore secreted by a distinctendocrine system which exists as separate glands inlower vertebrates but which has fused with the thyroidin mammals. Nothing is known, however, of the actionof calcitonin in non-mammals, so we cannot be sure thatits main action in these animals is similar to its action inthe higher vertebrates. But it is likely that it plays animportant role in calcium physiology in many vertebratespecies. Thus, the function of calcitonin is not yetunderstood and further comparative studies are neces-sary. Meanwhile, it is interesting to note that the dis-covery of a new endocrine gland (no everyday event)arose from experiments which were largely inspired byclinical observations.

99mTc: a Versatile IsotopeTwo qualities influence the choice of isotopes for

clinical use: the chemical characteristics of the elementor compound; and the physical properties of the

particular radioisotope. Technetium-99m (99mTc-mfor metastable) looked promising for diagnostic applica-tions because of its physical properties 24: it emits a

principal y-radiation of 140 keV, which is ideal for

scanning and external counting; it produces no primaryp-radiation, so the radiation dose to the patient is low,an advantage enhanced by a half-life of only six hours.The fulfilment of this promise was lately demonstratedat a meeting of the Society of Nuclear Medicine at

which no less than 32 papers dealing with 99mTc were17. Foster, G. V., MacIntyre, I., Pearse, A. G. E. Nature, Lond. 1964, 203,

1029.18. Pearse, A. G. E. Proc. R. Soc. B, 1966, 164, 478.19. Bussolati, G., Pearse, A. G. E. J. Endocr. 1967, 37, 205.20. Pearse, A. G. E., Carvalheira, A. F. Nature, Lond. 1967, 214, 929.21. Maurer, F. Morph. Jahrb. 1888, 13, 296.22. Copp, D. H., Cockcroft, D. W., Kueh, Y. Can. J. Physiol. 1967, 45, 1095.23. Tauber, S. D. Proc. natn. Acad. Sci. U.S.A. 1967, 58, 1684.24. Harper, P. V., Andros, G., Lathrop, K. A. Argonne Cancer Res. Hosp.

Rep. 1962, 18, 76.