A STUDY OF THE PHYSIOLOGICAL ACTIVITY OF ADENOMATA OF THE THYROID GLAND, IN RELATION TO THEIR IODINE CONTENT, AS EVIDENCED BY FEEDING EXPERIMENTS ON TADPOLES.
It seems evident from the foregoing experiments that the so called tumors (adenomata) of the thyroid possess the property of taking up iodine and metabolizing it into the active combination in the same way that the non-tumorous thyroid tissue does, although not so readily nor to the same degree, and the action on tadpoles of feeding desiccated tumorous thyroid tissue does not differ qualitatively from feeding desiccated non-tumorous thyroid tissue. The action in either case depends upon the iodine (active iodine) content, and in the case of the adenomata bears no constant relation to the state of their growth or differentiation. Examination of Tables II and III shows that in the main this is true. There are, however, certain discrepancies as to time of death, appearance of first forelegs, degree of emaciation, and rate of growth in certain dishes of the series, the action being not quite parallel to the iodine content. Some of these discrepancies may be explained in part by accidents of feeding, slight differences in size, age) and susceptibility of the different tadpoles receiving the same thyroid, and also by the variations in the amount of thyroid consumed by the different individuals in the same dish. Lenhart has shown that the action of the same thyroid varies with the quantity fed. Another important factor which has to be considered is the condition of the iodine itself. It was suspected at the time of these experiments that the iodine might be present in an active and an inactive form, but no satisfactory proof of this assumption, at the beginning of these experiments, was at hand. Support of this point has been afforded by the work of Kendall on the isolation of the active principle of thyroid and the separation of the iodine into two fractions. Since the completion of our experiments Marine has demonstrated by means of perfusion experiments in vivo and in vitro that iodine is rapidly taken up by the thyroid cells, and though the iodine increase in the perfused lobe may be 1,000 per cent in 2 hours as compared with the control lobe, yet the action on tadpoles is no greater. It then becomes an important question to determine the time required by the thyroid to take up inorganic iodine and manufacture it into the active thyroid principle. It is known that iodine is rapidly taken up by the thyroid, and in man the iodine content of the thyroid is subject to greater variations than in animals on account of the prevalent therapeutic use of iodine and the iodides in goiter and other conditions; even the iodine used in preparing patients for operations would increase the iodine content of the thyroid in a short time, so that one might expect such variations in the action of a given thyroid preparation fed to tadpoles as appear in these experiments. In this connection it is interesting to note (Table II) that Thyroid 20 with 4.31 mg. of iodine was only slightly more active than No. 5 with 1.31 mg. of iodine. Two possibilities have to be considered here. First, No. 20 may have active iodine slightly greater than 1.31 mg. and the balance present as inactive iodine. Second, No. 5 with 1.31 mg. of iodine might represent the maximum possible effect under the conditions of the experiment and a larger quantity of active thyroid iodine could produce no greater effect. Of course with the lower iodine contents the variations in effects might well come within the limits of errors of observation. Also the percentage error would be greater in the iodine determinations, accidents of feeding, etc. Our conclusions as to the effect of feeding desiccated thyroid to tadpoles agree in general with those of Lenhart. The action of the thyroid depends not upon a specific stimulus to differentiation but upon a stimulation of metabolism in general in proportion to the active iodine and the quantity consumed. High iodine contents produce rapid emaciation, at the same time resulting in differentiation even in tadpoles dying in 8 to 12 days. Low iodine contents result in differentiation at an earlier period than the controls. Tadpoles fed on thyroid with practically no iodine grow better than the controls, in this instance the thyroid acting simply as a food. Finally, the interest that the results of these experiments may have in connection with the question of function in tumor tissue should be pointed out. To those who hold that tumor lacks the capacity for physiological function, the adenomata of the thyroid could not be consistently regarded as tumors. To those who hold physiological function as a possible property of tumor tissue, the adenomata might be regarded as tumors. Future studies might warrant a recognition of different grades or degrees of tumor. On this basis the fetal adenoma (very little differentiation) might represent a higher degree of tumor than the diffuse colloid or simple adenomatous thyroid in which the adenomatous nodules are present to a great extent throughout the whole gland and are well differentiated. It is certain that there are all grades and degrees of growth and differentiation in the life history of fetal adenomata of the thyroid, from the pure fetal, undifferentiated adenoma with little or no iodine to the simple or colloid adenoma, well differentiated and with varying amounts of iodine approaching that of normal thyroid.
Graham
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H. K. Cushing Laboratory of Experimental Medicine and the Department of Surgery of Western Reserve University, Cleveland.