Relationship between the adrenal cortex and radiation sickness; a review of the literature and a presentation of new data.

Abstract

It has long been theorized that the adrenal gland is associated in some way with radiation sickness (4, 7, 10, 12, 19, 25, 27, 33, 34) or with some of the effects of radiation (15, 16, 19, 23, 25). In the earlier years, the adrenal medulla was studied extensively as a possible source of information (7, 19, 23); more recently attention has shifted to the adrenal cortex (4, 12, 15, 16, 25, 27, 33, 34), which as early as 1922 was suggested as a potential factor by Hirsch (10) and others. The theories on the relationship of the adrenal to radiation effects have been based on highly suggestive clinical, morphologic and pharmacologic findings. When these are assimilated in the light of present knowledge, the evidence becomes even more provocative. Some of the earliest work was done by Hirsch, who used anterior pituitary extracts and adrenal cortical extracts to prevent radiation sickness with some success, but found that posterior pituitary extracts had no apparent effect. Desjardins (7) quoted Tsuzuki as showing in 1926 that in rabbits given a lethal dose of radiation there could be demonstrated at autopsy (1) reduction of the fat content in the adrenal cortex, (2) degeneration of medullary cells, and, after extreme doses, (3) atrophy of the medulla. The highly significant work of Leblond and Segal (16) demonstrated convincingly that heavy irradiation of lymphatic tissue, with adequate shielding of the rest of the body, will produce hypertrophy of the adrenal cortex and involution of distant lymphatic organs, while in adrenalectomized subjects such involution does not occur. Martin, Rogers and Fisher (19) quoted Arrillaza and Izzo as describing a case of Addison's disease in which the patient died five days after receiving a routine series of x-ray treatments to a carcinoma of the tonsil. Attributing this to a lack of adrenalin, they heavily irradiated the remaining adrenal gland of a dog from which one adrenal had been removed. The irradiation was carried out through an operative wound, allowing a close target-subject distance. The dog suffered no ill effects, and autopsy twenty-six days later showed complete destruction of the adrenal medulla with viable islands of cortex surrounded by bands of fibrous tissue. Warren (33) reported that leukopenia and loss of lipoid from the adrenal cortex were common findings in the victims of the atomic bombing. He could not be sure, however, that these morphologic findings were not the result of “alarm” stimuli other than irradiation. Weichert (34) noted the striking similarity between Addison's disease and severe irradiation sickness and theorized that the toxic products of protein breakdown in irradiation produce a relative adrenal cortical insufficiency. He observed improvement in his patients after administration of desoxycorticosterone. Craver (4), from observations on mice, postulated that the adrenal cortex was necessary in some way to repair the general tissue damage resulting from irradiation.