MDDC - 1060 UNITED STATES ATOMIC ENERGY COMMISSION ■^Arr- ^?5-., SUMMARY OF IODINE PHYSIOLOGY AND METABOLIC STUDIES USING RADIOACTIVE ISOTOPES OF IODINE by J. G. Hamilton University of California This document consists of 3 pages. Date of Manuscript: October 18, 1944 Date Declassified: June 25, 1947 This document is for official use. Its issuance does not constitute authority for declassification of classified copies of the same or similar content and title and by the same author(s). Technical Information Division, Oak Ridge Directed Operations Oak Ridge, Tennessee SUMMARY OF IODINE PHYSIOLOGY AND METABOLIC STUDIES USING RADIOACTIVE ISOTOPES OF IODINE By J. G. Hamilton INTRODUCTION An excellent summary of the overall picture of iodine physiology has been compiled by Salter.' The total body content of iodine in adult humans over most regions of the world ranges from 20 to 50 milligrams of which approximately l/5th is present in the thyroid whose weight will average 25 g. Iodine in blood and tissue fluids is said to be somewhat less than 0.1 milligram per kilo. The value for muscle is stated to be of the order of 3 milligrams per kilo and comparable levels are indicated for the endocrine organs such as the pituitary, ovaries, adrenal cortex, and parathyroid glands. The intake of iodine per day is, of course, extremely varied and may range from less than 10 micrograms per day to almost a milligram per day. It is stated that in geographical regions of rela- tively low iodine content that approximately 25% of the eliminated iodine is excreted by way of the lungs, 50% via kidneys, and the remaining by way of the skin and hair. In the fasting state the fecal excretion is negligible. These values are conjectural to a certain degree and are only indicative of the endogenous metabolism of individuals who can be said to be in a state of iodine balance. TRACER STUDIES WITH RADIOIODINE A study of the absorption and excretion in normal human subjects indicates that this element is rapidly absorbed and rapidly eliminated.^ When from 50 to 100 milligrams of iodine are given orally to normal adult human subjects in the fasting state, approximately 50% is absorbed within the first 15 minutes from the digestive tract and within 1 1/2 hours over 90% has been absorbed. When a labeled dose of 14 milligrams is given to normal human adult subjects the iodine is almost exclusively ex- creted by way of the kidneys at an exponential rate, the half time being approximately 18 hours. ^ The uptake by the thyroid under these conditions for normal adult subjects averages 4% . These values have been confirmed by Chaikoff and his colleagues' in rats using radioiodine with inert carrier in comparable quantities. They made a careful analysis of the concentration of iodine in the soft tissues of the body, notably the small intestine, liver, and kidneys and found that the disappearance of iodine from these tissues was closely paralleled by the fall of labeled iodine in the blood. At the end of eight days the ratio of concentration of the iodine taken up by the thyroid to that in the soft tissues was the order of 10^, when the radioiodine employed had no added carrier. In these experiments the iodine concentrated in the endocrine organs was also investigated and found in all instances to be comparable to the iodine content of the blood and soft tissues noted previously. His group also made a detailed study of the uptake of iodine by the thyroid in rats, rabbits, sheep, and guinea pigs. With the exception of the rat, the average uptake by the thyroid gland of radioiodine without inert carrier at the end of 24 hours was approximately 20%. In the case of the rat the uptake was considerably greater and frequent levels in excess of 65% were encountered. Comparable studies with human subjects have given a value of 20% uptake for normal adults when iodine without carrier was used.' It is of considerable interest to note that at the end of 26 hours in both the thyroid and in the blood plasma approximately 90% of the radioiodine, when administered without carrier, has been converted into di-iodotyrosine and thyroxine.^ It will be remembered that these two organic iodine compounds MDDC - 1060 [ 1 2 ] MDDC - 1060 100 10 9 o z Q O < a: o 0.1 0.01 o '^ < V A X N \ \ N, X \ V ,. \, \ \ ' ' J^ e CHAIKOFF-RATS A HAMILTON AND SOLEY-MAN □ HERTZ- RABBITS X LE BLOND-RATS \ 'i \ \ \ \ N. \ V \ \ \ Q k ' \ V \ V .00001 .0001 .001 .01 .1 1 10 100 MG IODINE PER KG OF BODY WEIGHT Figure 1. MDDC - 1060 are amino acids, and are incorporated into thyroid protein, thyroglobulin, which, of course, comprises the principal protein in the thyroid colloid. This must, at least in part, explain the tenacity with which the thyroid holds its accumulated iodine and the difficulty with which the iodine thus stored can be washed out with the administration of inert iodine. In normal human subjects, when iodine without carrier was administered by mouth, the 20% which accumulated in the thyroid was retained for many weeks without significant loss. The very important relation of the thyroid uptake of iodine to the total quantity of iodine given in test doses is summarized in chart form (Figure 1). The values are taken from Chaikoff's work with rats,''° the experience of the author with human subjects at U. C. Hospital,^' ^''' the experiments of Hertz' and his assistants using rabbits, and the studies with rats reported by LeBlond.' The very rapid increase of iodine uptake by the thyroid with the decrease of weight of administered iodine is clearly apparent. It has been the experience of the author that the prior administration of iodine in man almost completely blocks the ability of the thyroid to accumulate radioiodine even when given in a total of less than 10"' grams of iodine. The time relationship between the administration of inert iodine and the subsequent tracer dose of radioiodine was never carefully studied with respect to the blocking ef- fect of the inert iodine upon the thyroid. However, it was apparent that this action of iodine lasts for a period of at least several weeks. The destructive effect of carrier-free iodine upon the thyroid tissue of rabbits and dogs without perceptible radiation effects upon any other tissues has been demonstrated.'' Complete destruction of the entire gland without either physiological or histological changes to the parathyroids in rabbits and dogs has been observed. The quantity of radioiodine required was 300 microcuries of I"' per kilogram which produced a thyroid irradiation of over 25,000 r. Smaller amounts of radioiodine without inert carrier have been employed in the treatment of a few cases of hyperthyroidism with complete and pro- longed remission of all of the clinical evidences of this type of thyroid disorder. The dose required ranged from 1 to 1.5 millicuries of I'^' (20 to 30 microcuries per kg of body weight). The internal thyroid irradiation was estimated to have been from 1000 to 3000 r. PROTECTION ASPECTS In order to protect personnel from absorbing radioiodine from the atmosphere it is estimated that 100 milligrams of potassium iodide should be taken each day. This amount should thoroughly block absorption by the gland of any significant amount of radioiodine. REFERENCES 1. Salter, W. T., The Endocrine Function of Iodine, Harvard University Press, p 113, 1940. 2. Hamilton, J. G., Amer. Jour, of Physiol. 124:667 (1938). 3. Hamilton, J. G. and M. H. Soley, Amer. Jour, of Physiol. 127:557 (1939). 4. Hamilton, J. G., Radiology 39:541 (1942). 5. Perlman, J., I. L. Chaikoff, and M. E. Morton, J. Biol. Chem. 139:443 (1941). 6. Morton, M. E., J. Perlman, and I. L. Chaikoff, J. Biol. Chemistry 140:603 (1941). 7. Hertz, S., A. Roberts, J. H. Means, and R. D. Evans, Amer. Jour, of Physiol. 128:565 (1940). 8. LeBlond, C. P., Revue Canadienne de Biol. 1:402 (1942). UNIV ERSITY OF fLORlDA 3 1262 08909 7439