NATIONAL INSTITUTES OF HEALTH CLINICAL STAFF case in these children, who had enlarged clinically to be solitary thyroid nodules in thyroid glands when treated, and it may be these children. That is the problem of that the nodule formation was induced in radiation-induced thyroid carcinoma. Two sorts of evidence have led to the clear dem- the children by whatever stimulus there is that causes the thyroid to grow to its adult size. Radiation injury in general may be onstration that irradiation is a contribut- ing cause in the development of thyroid expressed as the product of the degree of cell damage times the mitosis rate of the cancer. Although thyroid cancer can be produced in animals simply by prolonged thyroid stimulation resulting from iodine cells (26), and the child’s thyroid grows from about 2 g at age | year to 17 g in the deficiency or chronic administration of antithyroid drugs (29), there is abundant ex- adult (27). The role of thyroid stimulation by TSH in the nodule formation after irradiation is clearly indicated by the findings of Maloof (28). In rats treated with 1], hypo- physectomy or treatment with thyroxine prevented the cellular hypertrophy that was otherwise observed. It was of considerable interest that this treatment also greatly reduced the development of abnormalities in the thyroid cell nuclei (characterized by increase insize, irregularity, and hy- perchromatism), thus indicating that these changes were dueto cell stimulation rather than to irradiation per se. When thyroxine therapy was stopped, the lesions reappeared. This underscores the fact that thyroid radiation not producing obvious atrophy, inflammation, and fibrosis does not appear to cause any specific cell abnormality recognizable by ordinary histological examination. Last, I shall discuss the subject that was uppermost in the minds of those who ob- perimental Treatment that the roid irradiation (19, 20) just as it is by con- comitant treatment with a carcinogen such as acetaminofluorene (19, 29). As demonstrated by the experiments of Doniach (19), summarized in Table 11], the effect of 30 pc of 152] 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 Island children were exposed. It is of interest, also, that the radiation in Doniach’s rats increased the prevalence of multinodularity of the thyroid glands in response to maining in the operated cases, as well as in those not operated upon, unless this is prevented by the administration of suppressive doses of thyroid hormone. The ability Induction of Thyroid Tumors in Rats* Rats With Adenomas + 41 30 uc @I + MTU 1,100 rads X rays to thyroid 48 13 1,100 rads X rays + MTU to show goitrogen. The failure to find thyroid carcinoma in any of the Marshallese children can beattributed, it seems, to a happy chance. There remains a high likelihood that carcinoma would develop in the thyroid remnants re- None Methylthiouracil (MTU) 30 xc I (1,500 rads to thyroid) evidence prevalence is increased by antecedent thy- served the development of what appeared TABLE 11. Internal ‘Medicine no. 0 50 52 39 21 22 21 * From Doniach, I: Brit. Med. Bull. 14: 181, 1958 (19). With Adenomatous Replacement 47 4 With Carcinomas — 0 0 _ 27 1 11 1 0 0 17 0 0 7 Paap men eaethe 1238