—_o vur data ccliected on these features on all retients treated with I are Deing assexcled cn index cards so that many cf <hese consideraticns can pe ef—plores in the va otRe thoroughly studied clinica. result. oo5e IF a more precise esfimate <2 the needed can be achieved in each patient, nen pernaps therg@ can sé more correct doses given, fewer early cevelcoments cf hypethyroicism occurrfng anc Tawer onslances cr repeated treatments Deing recutred. The Development of Necclasms s= she Thyroid in Animals ane J. At leasttwo circumstances may have 21 important bearing on the developmen: of necrtiasms following 1311, One concerns the damage to the cell which rPsults in im pecrment to the manufacture and output cz thyroid normone, resulting ih a secccdary Stimulus to the gland. The other concerz:s the intrinsic nuclear damage that results in, impairment, abnormality, or even fail.re of cell division. In refaring here to damage to the nucleus it is important tc xeep in mind that the effecrq often sroduced are not rapidiy lethal to the cells; ravner the cells survive for long periocs with cr; mild impairment of function. If the development or benign or ignant neoplasms 1s dependent on chronic TSH stimulaticn then prolonged mild hypothyroddism shed be ar. important promoting factor. On the cther hand, if the cellular ge is sco de- VaScating as to cause severe hypothyroicism then that same damage woufd be sc cmcippline as tO hinder the development of a new growth which is dependent on ceJl divisisn. As is pointed out in two accompanying manuscripts, neoplasm fo ation in the rats resuires an interval of 14 to 18 months =rom the time of the irradiat on. The lengthy interval in man is clearly shown in the Marshallese where in spite of thoroug:. annual prysical examinations the first palpable nodule was not found for 9 y Pars anc:neoplasms yroid i:=.the are still appearing at 22 years. The maximal dose estimated to the Marsnallese was 1,100 rads in children and far less in the adults. cnildren exposed developed clinical hypethyroidism and that required f Tnis raises a question as to whether the estimate that has been made were irradiated at about 1 year of age. Of the 17 other children who were exposed under the age of 10, 15 did not display hypothyroidism but have developed neoplasms and been cperated. To date 6 carcinomas have been removed from 30 individualgq from several atol-: 3 Srem an atoll with extremely low expesure. Since this is a population whic. seldom ever develops thyroid nodules, the relationship to the radiation whidh was primarily racioiodines is most impressive. Our experience finding carcinomas in radioiodine treated patien Ss in the National An urcsually Cooperative Thyrotoxicosis Follow-up Stucsy seems to be quite contra an woulc nave been small number of carcinomas was found; in fact, considerably fewer surgery and found expected, considering the large number cr Graves' disease treated by tc have an occultcarcinoma. Such incidental lesions might have bee i= left in and +911 treatment given. Tne difference between the doss Mershallese thyroids and those of Graves’ disease is considerable if ic years of age are considered. Graves’ disease patients probably expectec to grow receives by the individuals beyonc ceive £5,230 to 12,000 rads while the Marshallese recei.zd less than 1,000, probably nearer 5259. Furthermore, the hyperplastic gland of Graves' disease is expected to be far more sensitive tc the radiation than the normal glands of the Marshallese. rats see to stronz Suggest that it is the smaller doses of 431] that produce circumsta es under which neoplasms arise. Indeed the effects are sufficiently mild so that b microscspic arChitectural distortion is recognized in animals most inclined to de lop neo>_asms.. Our animal experiments and the most _recent studies of others 1 \