1238 . a: SE “Chke: ee epee ie . NATIONAL INSTITUTES OF: HEALTH CLINICAL STAFF ma case in these children, who had enlarged thyroid glands when treated, and it may be . * = Annals of Internal Medicine The role of thyroid stimulation by TSH clinically to be solitary thyroid nodules in these children. That is the problem of radiation-induced thyroid carcinoma. Two sorts of evidence have led to the clear demonstration that irradiation is a contributing cause in the development of thyroid cancer. Although thyroid cancer can be produced in animals simply by prolonged thyroid stimulation resulting from iodine deficiency or chronic administration of antithyroid drugs (29), there is abundant experimental evidence to show that the prevented the cellular hypertrophy that roid irradiation (19, 20) just as it is by concomitant treatment with a carcinogen such as acetaminofluorene (19, 29). As demonstrated by the experiments of Dontach (19), that the nodule formation was induced in the children by whatever stimulus there is that causes the thyroid to growto its adult size. Radiation injury in general may be expressed as the product of the degree of cell damage times the mitosis rate of the cells (26), and the child’s thyroid grows from about 2 g at age | year to 17 g in the adult (27). in the nodule formation after irradiation is clearly indicated by the findings of Maloof (28). In rats treated with 17, hypophysectomy or treatment with thyroxine prevalence is increased by antecedent thy- was otherwise observed. It was of considerable interest that this treatment also greatly reduced the development of abnormalities in the thyroid cell nuclei (character- summarized in Table 11, the effect of 30 uc of 181] in the rat is similar to that of 1,100 rads of X-ray radiation. This is in the range of radiation dosage to which the Marshall ized by increase in size, irregularity, and hy- Island children were exposed. It is of interest, also, that the radiation in Doniach’s perchromatism), thus indicating that these changes were due to cell stimulation rather than to irradiation per se. When thyroxine therapy was stopped, rats increased the prevalence of multinodularity of the thyroid glands in response to goitrogen. the lesions reap- peared. This underscores the fact that thy- The failure to find thyroid carcinoma in any of the Marshallese children can he attributed, it seems, to a happy chance. There remains a high likelihood that carcinoma would develop in the thyroid remnants re- roid radiation not producing obvious atrophy, inflammation, and fibrosis does not appear to cause any specific cel] abnormality recognizable by ordinary histological examination. Last, I shall discuss the subject that was uppermost in the minds of those who observed the development of what appeared TABLE 11. maining in the operated cases, as well as in those not operated upon, unless this is prevented by the administration of suppres- sive doses of thyroid hormone. The ability Induction of Thyroid Tumors in Rats* Treatment Rats None Methylthiouracil (MTU) 30 we IT (1,500 rads to thyroid) 30 pe MII + MTU 1,100 rads X rays to thyroid 41 50 52 48 13 With Adenomas With Adenomatous Replacement With Carcinomas “10. 22 * From Doniach, I: Bret. Med. Bull. 14: 181, 1958 (19). 3G4}2840 21 0 0 0 27 I 17 0 0) 0 11 1 7 Te ee FFee ee 1,100 rads X rays + MTU 0 39 21 47 4