NATIONAL INSTITUTES OF HEALTH CLINICAL STAFF subjects. In others, there appeared to be partial destruction with the result that TSH secretion was increased; and the glands, although maintaining normal oral- most normal hormone production, were operating at their maximal ability. They could not respond to further TSH stimulation. The possible relationship between this state of affairs and the formation of thyroid nodules will be considered in the next discussion. RADIATION EFrects on THE Toyrow GLAND The foregoing presentation has clearly shown radiation of the thyroid gland by isotopes of radioiodine to be a major feature of the late results of exposure to radioactive fallout. I shall now discuss the subject of thyroid radiation. This subject takes on practical importance in the etiology of certain thyroid tumors and in theclinical use of iodine isotopes for diagnosis and therapy of thyroid diseases. Roughly during the period over which the Marshall Island observations have extended and to some extent before that time, a considerable number of experimental andclinical observations on this problem have been published and have been the subject of several reviews, notably by Doniach (19) and by Lindsay and Chaikoff (20). This work has led to at least a general understanding of radiation-induced thyroid abnormality. As demonstrated by the Marshall Islanders, the abnormalities fall into two cate- gories—one related to interference with thyroid cell function and the other concerned with the development of neoplastic changes. The Marshall Island findings also demonstrate very well the interplay between these two radiation effects. In clinical practice, one of the major uses of radioiodine is to produce destruction of thyroid tissue—either the normal gland in patients with intractable angina pectoris, the hyperplastic gland in hyperthyroidism, or neoplastic tissue in metastasizing thyroid carcinoma. Since retention of iodine in the Internal Medicine thyroid gland is unique among mammalian tissues, complete destruction can be readily attained by administering a suitably large dose of the isotope. This is achieved with a dose delivering about 50,000 to 75,000 rads. The thyroid tissue is then subject to acute radiation injury, with subsequent in- flammation, tissue destruction, and fibrotic healing. This is the desired end result in heart disease and in thyroid carcinoma. In hyperthyroidism, however, the usual aim is to leave the patient with sufficient thyroid function to achieve euthyroidism. By properly adjusting the isotope dosage, this aim can be achieved in a high percentage of patients given about 10,000 rads to the gland. Studies of these patients after partial thyroid destruction have led to some interesting observations. Injury to the various thyroid metabolic processes may not be uniform. Thus, in some of the patients the accumulation of radioiodine by the thyroid gland remains greater than normal although hormonesecretion falls to normal or below. This is due to an injury to the iodine organification mechanism exceeding that to the iodide transport system (17, 18). As discussed earlier, the trapped but nonorganified iodine can be demonstrated by discharging it with an ion such as perchlorate, which competes with iodide for membrane transport. Other examples of uneven metabolic injury have not been described but probably exist. On the other hand, thyroid function with respect to iodine metabolism and hormone production may appear to be normal in every respect, although the cell is gravely injured. This phenomenon has aroused considerable interest in recent years because only long after successful radiotherapy does this injury become manifest by the late onset of hypothyroidism (21, 22). One possible explanation for this phenomenon is that the radiation has led to lethal mutations in the chromosomes of the thyroid epithelial cells without damageto the rela- PareeReet 1236