Minin ites Anica alien tliat Sits, -teteiinatilln, Tia aia nen ll ae eei ie eae dm al Mle pe ae 42 it simultaneously acts as a carcinogen and, by im- pairing the functional capacity of the gland, in- duces TSH secretion and thyroid stimulation. The high incidence of adenomatousgoiters and hypothyroidism in the more heavily irradiated children exposed at <(10 years of age, compared with no abnormalies in some 100 children in the same age range in the less exposed and unexposed groups, leaveslittle doubt about the etiological relationship of these lesions with irradiation exposure. The higher incidence in children mayberelated to increased sensitivity of the child’s thyroid to irradiation butis probably related moredirectly to the relative magnitudes of the radiation doses received, the small child’s gland probably having received 5 to 10 times the radiation dose received by the adult’s gland. Since most of these lesions appeared in teen-age children, puberty may have been a contributing factor. The incidence of the lesions in female childrenis only slightly greater than in male children (1.27 to 1). A greater prevalence of thyroid abnormalities in that sex is correctly noted. The increased incidenceof thyroid abnormalities, including one case of malignancy, in the adults of the more heavily exposed Rongelap population makes it necessary to considerseriously radiation exposureas the etiological factor. In Appendix 7 statistics on thyroid malignancies in the Marshall Islands and the Trust Territory are presented. A low incidenceofsolitary nodules was noted in older (>>50 years of age) unexposed Marshallese of both Rongelap and Utirik Islands. The single nodule case in the less exposed 46-yearold Ailingnae woman, on the other hand, may well fall into the category of the sporadic type, since the nodule was well encapsulated, and the remainderof the thyroid gland appeared normal. 500832b Urine analyses indicate that iodine intake is adequate. The incidence of nodules and sporadic cases of goiter seen at the Majuro Hospital* is low, and the Marshallese population showsno evidence for goitrogenic factors in their environment. The sensitivity of children’s thyroid glands to the developmentof neoplastic changes from radia- tion exposure has been amply demonstrated. A series of retrospective and prospective studies have clearly shown the causal relation of irradiation of the neck region in infants and later development of thyroid cancer.°* ** Althoughthecalculation of the dosage in the Marshallese is subject to large uncertainties, the greater incidence of pathological changes in the glands of the Marshallese maybe related to a greater dose of radiation received by their thyroid glands. Lesions similar to those seen in the Marshallese have been reported in children 39 to Il years old after treatment with ‘°’! for thyrotoxicosis.°*** Doniach® points out that cell division in the growing thyroid gland of the child may be a factor in the increasedsensitivity to irradiation. There appears to be an increased incidence of thyroid carcinomain inhabitants of Hiroshima and Nagasaki exposed to radiation from the atomic bombexplosions.*° These people were exposed to varying doses of external radiation to the thyroid gland but not to internal exposure from radioiodine. It has been assumed that the slight growth retardation previously noted in some of the exposed children was due to radiation, but the mechanism has been obscure. The growth hormone studies suggested that pituitary function was normal, X rays of the sella turcica showed no evidence of pituitary abnormality. With the recent development of hypothyroidism in twoof the most growthretarded boys and evidence of mild hypothyroidism in several other children with thyroid nodules and growth retardation, a hypothyroid etiology seems mostlikely. Elevated TSH levels indicate that the hypothyroidism is primary. Minimal hypofunction of the gland may have been missed in the past, since the apparently normal PBI levels may have been spuriously high, the true thyroxine level being masked by the elevated iodoprotein component characteristic of the Marshallese. *In March 1966, twocases of goiter with large, nodular giands were seen at the Majuro Hospital. One mayhave had mild hyperthyroidism. These cases were not part of the population under study. ae noma formation in the remaining thyroid tissue 2 years later.°*-*? All these procedures produce hypothyroidism which serves as an effective stimulant to the secretion of TSH by the pituitary gland. The thyroid gland under the influence of TSH first undergoes diffuse hyperplasia and hypertrophy and adenomaformation. In the cases of iodine deficiency and partial thyroidectomy, it is probable that no drug or carcinogenic agentis involved. The incidence of carcinomas after a combination of carcinogenic agents (such as radiation or acetylaminofluorene) and anyfactor that causes hypothyroidism is much higher.** Radiation by either x rays or ‘*'] is particularly effective, since ah ectomyin the rat has been reported to cause ade-