LATE EFFECTS OF RADIOACTIVE IODINE IN FALLOUT 1237 tively small numberof genes regulating the synthesis of proteins responsible for thyroid net result could be the development of mild hypothyroidism or the maintenance roid gland occurs very rarely, and mitosis of the normal gland. Consequently, the tinued overstimulation by TSH. Under such circumstances, those cells capable of responding may grow and multiply. Fur- very long time. After many years, the cell thermore, if the radiation has produced a nonlethal mutation, the progeny of the cell lethal mutation may not be evident for a begins to divide and perishes in the process. The cumulative effect of cell death could readily account for the observed accrual of hypothyroid cases at the rather steady rate of about 2%/year of those treated. Thus, it is not unexpected to find thar hypothyroidism developed insidiously in certain of the exposed Marshallese children. _ The radiation dose was not so large as to cause extensive cell destruction in the acute phase, but only later did the injured cells succumb. The twoclearly hypothyroid Marshallese children, like patients developing hypothyroidism after radioiodine therapy for hyperthyroidism, did not have any goiter forma- tion. Evidently, the cells are sufficiently injured in these instances so that they fail to respond to the influence of the excess TSH secretion that must accompany falling thyroid function. This phenomenon was demonstrated directly by Doniach (23) who showed that rats treated with 30 ye 171, or 1,100 rads by X rays, fatled to develop goiter when treated briefly with propylthiouracil. Maloof, Dobyns, and Vickery (24) also observed this phenomenon and. postu- lated that, since the stimulated glands showed cellular hypertrophy but no increase in weight, there must have been an impairment of the ability of such irradiated cells to divide. In the spectrum of radiation dosage tothyroid cells, one might expect to find the situation in which the cell’s function is partially impaired but its growth potential is not. Alternatively, unequal damage to This chain of events appears responsible for the majority of the cases of thyroid abnormality among the Marshall Islanders and is found in animals treated with appropriate doses of radioiodine especially when further stimulated by low-iodine diet or antithyroid drugs (19, 20). As pointedout in connection with the histological findings, the thyroid glands of the exposed Marshallese children showedresults characteristic of excessive and prolonged thyroid stimulation. Such stimulation, with or without preceding irradiation, leads to the formation of thyroid nodules with a wide variety of histological cell types. Nodular goiter formation of this sort, however, is not limited to children. The explanation for the high prevalence of goiter in the children and the much lower prevalence in the exposed adults is most likely attributable to the fact that the small thyroid glands of the children received a larger, and hence more destructive, dose of radiation. Sheline, Lindsay, McCormack, and Galante (25) also found in their follow-up of patients treated with thyroid radiation for thyroid disease that of the 8 patients de- veloping thyroid nodules out of a total of 256, 6 had been irradiated before the age of 20 years and 4 before the age of 10 years. Indeed, the latter 4 represented two thirds of all those treated at an age younger than 10 years. Most of them had multiple nodules, much as were found in the Mar- shall Islanders. It may be that these younger subjects actually received larger radiation doses than the older ones. On the other hand, this seems unlikely to be the ope me aetee cells in the same gland may result in some with impaired function and growth potential and others with less severe injury. The may be abnormal. oer is almost never seen in histological sections of euthyroidism only as a result of con- maeeepel cell function. Cell division in the adult thy- 8a Te Tee Talend No6 so Teme * 31428345