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The Use of Radioactive Iodine in Studying the Pathologic Physiology of Thyroid Disease

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The Use of Radioactive Iodine in Studying the Pathologic Physiology of Thyroid Disease THE USE OF RADIOACTIVE IODINE IN STUDYING THE PATHOLOGIC PHYSIOLOGY OF THYROID DISEASE Rulon W. Rawson J Clin Invest. 1949;28(6):1330-1346. https://doi.org/10.1172/JCI102200. Research Article Find the latest version: https://jci.me/102200/pdf THE USE OF RADIOACTIVE IODINE IN STUDYING THE PATHOLOGIC PHYSIOLOGY OF THYROID DISEASE BY RULON W. RAWSON (From the Memorial Hospital and the Sloan-Kettering Institute, New York City) It was in May, 1938 that Hertz et al. (1) pub- to our knowledge of human thyroid disease by lished the first report on biological studies with a studies with radioactive iodine. radioactive isotope of iodine. By today's stand- The earliest studies done at the clinical level ards these first studies were done under the least by Hamilton and Soley (3) reaffirmed our previ- favorable conditions with an isotope whose half ous concepts that the human thyroid has an avidity life of 25 minutes limited the studies that could be for iodine. These investigators compared the col- done. Notwithstanding the limitations put on lection by the thyroid of iodine labelled with radio these investigators they not only reaffirmed cer- iodine and its excretion in the urine and feces in tain principles of thyroid physiology, but with normal subjects and in patients having various other investigators, Hamilton (2), Hamilton and thyroid disorders. They found that an orally Soley (3), and LeBlond and Sue (4), who began administered dose of labelled iodine was absorbed working with radioactive isotopes of iodine in rapidly and could be detected in the thyroid within other laboratories at about the same time, they 20 minutes. In normal subjects 74 to 89 per pioneered in a new field of investigating the thy- cent of the dose was excreted during a five-day pe- roid. Today we have a small army of investigators riod with the major portion appearing during the bringing together a variety of disciplines, i.e., first 24 hours. Two myxedematous patients ex- physics, chemistry, embryology, physiology, histo- creted 91 and 94 per cent in the urine during five chemistry, pathology and clinical medicine in days but at a much slower rate than did the nor- studying with radioactive iodine and other tools mals. Thyrotoxic patients previously treated with normal and morbid physiology of the thyroid. iodine excreted about the same amount of iodine Many of these investigators are students whose as did normal individuals. Fecal excretion of primary interests are related to studies of normal these labelled doses of iodine averaged only about and abnormal function of the thyroid. These stu- 1 per cent of the dose. In another series of studies dents are delighted to have made available so Hamilton and Soley (5) recorded the character- many new technics with which to increase our istic collection curves obtained by in sivo meas- knowledge of thyroid physiology. Many of the urements for various thyroid states. The curve investigators in this field are interested primarily that they observed to be typical for normal thyroids in isotopic methods and their application to stud- was a smooth curve which leveled off to a flat ies in biology. They probably have been attracted plateau in two days. The initial collection by thy- to this field because of the unique avidity of the roids of hyperthyroid patients was greater and thyroid for iodine which makes this an ideal tis- much more rapid than in normal thyroids but de- sue for applying isotopic methods, and for study- creased almost as rapidly to a plateau lower than ing the biologic effects of irradiation with such that of the normal thyroids. This phenomenon isotopes. was also observed in two goiterous hypothyroid At the present time, it seems quite proper to children (Hamilton, et al. [6]). This rapid de- ask questions such as those posed by Dr. William crease to a lower than normal plateau following T. Salter preceding the 1948 Symposium on Radio an increased pickup observed in the goiterous Iodine at the Brookhaven National Laboratory. children and hyperthyroid individuals might be "1. How has radio iodine improved our knowledge attributed to the fact that these investigators were of iodine metabolism and of the physiology and using 14 mgm. of inert iodide as carrier. This the therapy of the thyroid? 2. How do the results concept is supported by their failure to observe the harmonize with past experience?" The purpose rapid loss of radio iodine from the thyroid when a of this paper is to review the contributions made carrier dose of 0.1 pg. of sodium iodide was given. 1330 USE OF RADIOACTIVE IODINE IN THYROID DISEASE STUDY 1331 This explanation is further supported by the ob- Keating et al. (10) followed the rate of radio- servations of Hertz et al. (7) who administered active iodine excretion in patients who had re- radioactive iodine with varying amounts of car- ceived 100 microcuries of I131 with 100 Mig. of car- rier iodide to patients suffering with Graves' dis- rier iodine. By mathematical analysis their uri- ease at varying stages of preoperative treatment nary excretion curves yielded four quantities: 1. with potassium iodide. They observed that the The renal fraction (that fraction of the dose ex- untreated hyperplastic thyroids of Graves' disease creted in the urine) ; 2. The disappearance rate collected 80 per cent or more of the labelled iodine (the proportional rate of disappearance from the if the dose was small. They also observed that blood); 3. The renal excretion rate; and 4. The with increasing time intervals after the adminis- collection rate (the proportional rate of disap- tration of isotopic iodine there was an increasing pearance into other sites than the kidneys which amount of radioactive iodine in the thyroxine-like they interpreted as an index of thyroid collection fraction of the gland. rate). They found the renal fraction to be greater Since these comparatively earlier observations, than normal in hypothyroid patients and less than a number of investigators have used isotopic tech- normal in hyperthyroid patients. The disappear- nics in studying the role of iodine in normal and ance rates they found to be less in hyp6thyroid abnormal thyroid physiology. patients and markedly greater than normal in pa- Chapman et al. (8) have studied the collection tients having hyperthyroidism. The most signifi- of radio iodine by the human fetus. They ad- cant variation that they observed was in the col- ministered tracer doses of J131 12 to 48 hours be- lection rates which were much less than normal fore operation to pregnant women who because of in hypothyroid states and averaged six times the organic disease were coming to therapeutic abor- normal in hyperthyroid patients. tion. The intact fetus was fixed in formalin and These marked variations from normal in the then sectioned longitudinally, one half was taken collection of iodine by the thyroid or the urinary for measurements of radioactivity and the other excretion of radio iodine in hypothyroidism and in half was examined histologically. They observed hyperthyroidism have prompted many investiga- that fetuses less than 12 weeks old did not con- tors to use such methods of study as a means of centrate any measurable amount of labelled iodine. diagnosing abnormal states of thyroid function. In those fetuses which varied in age from 14 to 32 Quimby and McCune (11), who used in vivo weeks the thyroids showed an avidity for iodine measuring technics, found that children who clin- which seemed to increase with the age of the fetus. ically were euthyroid concentrated and retained in It is of interest that these investigators were able their thyroids about 12 per cent of an adminis- to confirm the opinion that the onset of function as tered dose of radio iodine. They found that hy- measured in this manner is correlated with the perthyroid children concentrated and retained sev- appearance of definite follicles containing colloid. eral fold the value obtained in euthyroid children Astwood and Stanley (9) studied the rate of ac- whereas hypothyroid children concentrated as cumulation of radioactive iodine by the thyroid in little as 1 per cent or less of the dose. McArthur 70 normal humans. By plotting the counting rate et al. (12) followed the urinary excretion of radio per second obtained at a standard distance from iodine in a series of patients and observed the uri- the thyroid against the square root of the elapsed nary excretion of 22 thyrotoxic patients to aver- time in minutes they were able to plot a straight age 25 per cent; of 30 non-thyrotoxic patients line which continued for about eight hours from to average 60 per cent. They reported that this which they were able to determine an accumula- method of study was of real value in excluding the tion gradient. In normal humans they found this diagnosis of Graves' disease in patients having accumulation gradient to vary between the limits hypermetabolism due to alcoholism, anxiety, com- of 1.5 and 36.4 with a mean of 9.3. Myxedematous pensated hypertensive cardiovascular disease, patients were found to have accumulation gradients Parkinsonism, pheochromocytoma and thyrotoxi- of 0.5 to 1.9 and thyrotoxic patients receiving no cosis factitia. treatment at the time of testing were found-to have Feitelberg et al. (13) have described a method gradients which varied between 17.0 and 43.6. for measuring and recording localized collections 1332 RULON W. RAWSON of radio iodine. It is of interest that with this the effect of thyroid-stimulating hormone on these method they were able to demonstrate a function- gradients. They observed that for eight hours ing lingual thyroid. after the injection of hormone no effect on the rate Werner et al.
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