OR a neeT ee ta -42. Indirect Effects Mediated Through the Endocrine System The thyroid gland is one of the several endocrine organs qf the body whose activity is interdependent upon and responsive to disturtfance in the functions of other members of the system. For example, whan thyroid function is suppressed, there is characteristically an increasdd produc- tion by the pituitary gland of a hormone that stimulates the c@lls of the thyroid. This mechanism is the basis of an hypothesis that haq been ad- vanced to explain the production of thyroid cancer by agents whose primary effect is to impair thyroid function. The resulting over-stim unimpaired or slightly damaged cells by pituitary hormone is pye first induce hyperplasia or other effects which may then occasj progress to true neoplasia, In the case of human beings irradiated as infants or chil incidence of thyroid neoplasms rises sharply during puberty and adolescence, The high requirement for thyroid function during this period of life presumably plays a powerful secondary role in inducing neoplastic ransformation of the irradiated gland. The incidence of radiation-indud ad thyroid disease in this group appears to fall off after age 20 to 25 ye ars. 3. Other Indirect Effects in Cancer Induction In the last report of this group, it was stated that the fp obability of developing thyroid cancer after irradiation is influenced b factors other than endocrine effects or the direct action of radiation k in the thyroid gland itself. The reasons for this statement ware twofold: received comparable doses of X-rays to the thyroid but differe to tissues other than thyroid. In the past four years, the data on which these conclusiors were based have been reconsidered in the light of new estimates of thyroid doses in these cases under study. The radiation dose to the tHyroid depends strongly upon the exact location of the gland with respect to the primary beam, as well as upon the air dose. By estimating thywoid dose using reasonable assumptions as to beam port placement, it is pflossible to show a strong dose response for radiation-induced thyroid n@oplasms. Furthermore, the remarkable variation in incidence of thyroid dancer in selected groups of persons who received comparable air doses of tions of the geometrical relations to the primary beam. Although the possibility that irradiation of other tissues may have influende tumor induction cannot be excluded, it is not necessary to invdke this hypothesis to explain the observations. 4&. Diagnostic and Therapeutic Exposure to X-raq2OE ARCHIV a. Diagnostic X-ray In various diagnostic procedures such as radiography fof the teeth,