Pea a ae Te le ek peepee 7 waste ee -42. ‘Indirect Effects Mediated Through the Endocrine System The thyroid gland is one of the several endocrine organs of the body whose activity is interdependent upon and responsive to disturbance in the functions of other members of the system. For example, when thyroid function is suppressed, there is characteristically an increased production by the pituitary gland of a hormone that stimulates the cells of the thyroid, This mechanism is the basis of an hypothesis that has been advanced to explain the production of thyroid cancer by agents whose primary effect is to impair thyroid function. The resulting over-stimulation of unimpaired or slightly damaged cells by pituitary hormone is presumed to first induce hyperplasia or other effects which may then occasionally progress to true neoplasia, In the case of human beings irradiated as infants or children, the incidence of thyroid neoplasms rises sharply during puberty and adolescence. The high requirement for thyroid function during this period of life pre- sumably plays a powerful secondary role in inducing neoplastic transformation of the irradiated gland. The incidence of radiation-induced thyroid disease in this group appears to fall off after age 20 to 25 years. 3. Other Indirect Effects in Cancer Induction In the last report of this group, it was stated that the probability of developing thyroid cancer after irradiation is influenced by factors other than endocrine effects or the direct action of radiation absorbed in the thyroid gland itself. The reasons for this statement were twofold: first, the apparent absence of a dose response in thyroid cancer in persons treated with a wide range of dosage; and, second, the remarkable variation in thyroid cancer incidence in selected groups of children who received comparable doses of X-rays to the thyroid but different doses to tissues other than thyroid. In the past four years, the data on which these conclusions 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 thyroid dose using reasonable assumptions as to beam port placement, it is possible to show a strong dose response for radiation-induced thyroid neoplasms. Furthermore, the remarkable variation in incidence of thyroid cancer in selected groups of persons who received comparable air doses of X-rays can be explained by the variation in thyroid dose resulting from variations of the geometrical relations to the primary beam, Although the possibility that irradiation of other tissues may have influenced thyroid tumor induction cannot be excluded, it is not necessary to invoke this hypothesis to explain the observations. 4. Diagnostic and Therapeutic Exposure to X-raf2OE ARCHIVES a. Diagnostic X-ray In various diagnostic procedures such as radiography of the teeth,