88 Harold L. Atkins situation, albeit somewhat more mild, exists relative to surgical treatment. A means to reduce post-therapeutic hypothyroidism may be found when there exists a better understanding of the etiology of this complication. A thesis for the effects of }*"I has been proposed by Greig.?” The reproductive capacity of thyroid cells is more radiosensitive than the functional capacity. However, damage to the reproductive capacity is not manifest until the cell attempts to undergo mitosis, which may not occur for some years following "I. Somecells may die immediately. With time there is an increasing stress on the remainingcells with shortening oflife span and inhibition of DNA synthesis under the influence of thyroid stimulating hormone.”® These cells then attempt to divide but die in the process, eventually resulting in hypothyroidism. Another possibility is related to the well-known late effects of radiation on blood vessels. The delayed developmentof endarteritis obliterans can result in the deprivation of an adequate blood supply to the gland. This, in turn, would lead to reduced function and/or cell death. Early hypothyroidism occurs when all the thyroid cells have received a lethal dose of radiation. Usually, however, the dose distribution is uneven throughout the gland resulting in a frequency distribution of radiation injury. The most marked irregularity in distribution of radioiodine occurs in nodular glands accounting for the relative radioresistance of these glands and the low incidence of postradiation hypothyroidism. Hypothyroidism developing late after partial thyroidectomy remains unexplained in the light of the above thesis. It is possible that the remnant of gland is put under severe stress to maintain a normallevel of function and eventually is ‘*exhausted.’’ Another factor may be increased scarring and consequentreduction in blood flow to the gland. These possibilities are generally unsatisfactory explanations when considered along with the accumulated experience in this field. There is now important evidence that hyperthyroidism, like Hashimoto's thyroiditis, is a disease related to a defect in the autoimmunesurveillance mechanism.”**! Although it is thought to be primarily a disease involving cell- mediated immuneprocesses, humoral factors mayalso play a role.*?*** Except for some mildly positive evidence in those patients developing postsurgical hypothyoidism, as stated above, the role of autoimmunity in post-therapeutic hypothyroidism is unclear. However, it has been suggested that with both surgery and radiation, partial destruction of the gland releases more thyroidal antigens, in turn leading to eventual complete destruction of the gland.’ It is difficult to determine the natural course of hyperthyroidism in the untreated individual in the modern era. Spontaneous remissions occur butthe disease can readily have a fatal outcome. It is estimated that only about | percent of such cases would end up as hypothyroid.* Therefore, the high incidence of late hypothyroidism cannot be attributed to the natural history of the disease or considered a fortuitous occurrence. Mostlikely it is related to the underlying etiology of the disease as well as to the treatmentofit. THERAPEUTIC STRATEGIES CFE Attempts to deal with the high incidence of postradioiodine hypothyroidism were energetically pursued by many investigators once this major complication