Symposium on Current Concepts of Thyroid Disease

Radioactive Iodine Therapy Kenneth Sterling, M.D.*

Radioactive iodine has been in use since the pioneering studies of Hertz in Boston, in 1938 and 1939. Similar work was carried out in Berkeley, and publications date back as far as 1940. Within a few years a great deal of information regarding iodine kinetics in the thyroid gland, thyroid hormone economy in general, and also the use of radioactive iodine in treatment had been learned in a preliminary way. With the availability of the atomic pile or nuclear reactor in 1946, 131 1, the isotope most widely used in diagnosis and therapy, was made available to many institutions and radioactive iodine therapy began to see widespread use. Initially this treatment was confined to individuals in the older age groups, that is, in the fifth or sixth decades of life or beyond, on the presumption that isotope therapy might conceivably prove carcinogenic. Radioactive iodine therapy was also preferred when significant contraindications to surgical resection existed, such as heart failure, and many other complicating medical problems in addition to old age. As enthusiasm for radioactive iodine increased, it became the preferred therapy in many clinics and was often given as the first choice to individuals above the age of 35 or even 30. In certain areas it has been given at all ages, even in the pediatric group, but there appear to be at least two reported malignancies associated with prepubertal administration of 131 I so that the majority of clinics advise initial use of radioactive iodine over the age of 30 or 35 years with one significant exception. In toxic recurrent goiter following unsuccessful surgery, it has been considered reasonable to administer 131 I at any age since the problem of a second operation after a previous thyroidectomy is ordinarily much more difficult technically in view of the cicatrization, irregular thyroid re growth and other difficult mechanical factors. 7 The Cooperative Thyrotoxicosis Therapy Follow-up Study has provided information from over 36 thousand patients with about 99 per cent successful follow-up for more than two decades. The small incidence of malignancy after surgery and after 131 I therapy implied that ':'Clinical Professor of Medicine, Columbia University College of Physicians and Surgeons; Medical Investigator and Director, Protein Research Laboratory, Veterans Administration Hospital, Bronx, New York

Medical Clinics of North America- Vo!. 59, No. 5, September 1975

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the "risk from 131 I is not significant," a conclusion which should provide desired reassurance with regard to use of radioactive iodine. 2 The enthusiastic use of radioactive iodine as the preferred modality of therapy was tempered by the observations of increased incidence of late hypothyroidism observed in many clinics but probably most strikingly brought out by the report of Einhorn.4 Since that time, efforts have been made to diminish the incidence of late hypothyroidism with a variety of approaches. One thing which has become quite clear is the inadvisability of giving a second dose of 131 I before the major effects of the first dose have become fully apparent. Some of the early enthusiasts were known to give a second drink of 131 I as soon as 2 or 3 months after the initial drink which seems most likely to increase the hazard of eventual hypothyroidism. Although beneficial effects following 131 I may be observed within a matter of several weeks, it is by no means unusual for a period of 5 or 6 months to be required before a relatively balanced view of the patient's course can be appreciated. For this reason it has become widespread practice to employ much smaller initial doses than were undertaken in the 1940's and 1950's. An average dose might be 3 mCi rather than 7 mCi. It is advisable to avoid repeating the dose any sooner than 6 months, and more often to wait a full year before giving a second radioactive iodine treatment. In the intervening periods prior to administration of radioactive iodine and also prior to its initial therapeutic effect, it is common practice to employ an antithyroid drug regimen so that it is entirely possible to achieve euthyroid status within a few weeks after completion of the initial work-up of the patient regardless of the possibility that two or more doses of 131 I may be spaced out at 6 months or even 1 year intervals. When 131 I is prescribed the antithyroid drug regimen is interrupted from 3 days before to 3 days after the scheduled administration of isotope to prevent interference with uptake. Twenty-four hour uptake values should be obtained with all therapeutic doses to assure that the isotope has been taken up by the gland and that no unexpected interfering event has occurred, such as the patient vomiting or the utilization of pyelography. Since the accumulation of reports concerning the late incidence of hypothyroidism after 131 I therapy, some papers have suggested a late rise in incidence, perhaps continuing indefinitely, so that theoretically all patients might ultimately become hypothyroid if they survived long enough. The present writer does not share the view that the incidence of late hypothyroidism rises indefinitely but believes it tends to plateau after a decade or two. Nevertheless, all patients should be fol1"wed at least biennially.7 The soft x-ray emitting isotope, 125 1, was introduced in the hope that the less penetrating irradiation might destroy mainly the secretory portions of thyroid acinar cells without causing necrosis by destruction of nuclei in the basilar portions of the cells, and hence be associated with a lower incidence of hypothyroidism. Although the theory was attractive, and there were some initial enthusiastic reports, more prolonged experience has not been encouraging. Therefore, 125 1 would seem distinctly less desirable than 131 1 as a therapeutic modality. 1

RADIOACTIVE IODINE THERAPY

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An antithyroid regimen is indispensable for the management of hyperthyroidism during the long periods required for maximal effects of radioactive iodine therapy. Some clinics, notably the Thyroid Clinic of Massachusetts General Hospital, have administered iodide (50 to 150 mg per day) for suppression of thyrotoxicosis while awaiting the full effects of 131 I. While this may often suffice, we have preferred the use of the thiourea group of drugs, methimazole (Tapazole) and propylthiouracil. We usually recommend a blocking dose of methimazole as a single daily dose (usually 80 mg, infrequently 100 or 120 mg) and add 50 or 75 fLg triiodothyronine (Cytomel). On such a regimen, euthyroid status is usually attained within a few weeks, and the serum T4 will be depressed well below normal. In evaluation of the need for further 131 I, the methimazole is stopped while oral Ta is continued. If the serum T4 concentration remains below normal, it almost invariably signifies that a long term remission is at hand. If, on the other hand, the suppressed T4 values rise progressively despite continued oral administration of Tl, this signifies the need for additional 131 1 therapy. Thus the serum hormone levels may be employed most conveniently to evaluate the need for further doses of 131 I, rather than carry out serial tracer uptakes. Follow-up determinations of uptake may not be particularly helpful, since, for example, a small thyroid remnant may be turning iodine over rapidly, and may sometimes give a high 24 hour uptake value despite euthyroid status. Serum hormone levels plus careful clinical evaluation give the best guidance to deciding the need for supplemental doses of 1311. When in doubt, it is usually better to temporize for an additional period on antithyroid drug maintenance. A major consideration in radioactive iodine therapy is, obviously, the selection of a proper dose of the isotope. As stated above there has been a growing awareness of the problem of late hypothyroidism which may occur insidiously a decade or more after the control of the hyperthyroidism. If follow-up could be 100 per cent this would constitute less of a problem since replacement therapy is fully effective. At a cost of three or four cents a day the patient could take desiccated thyroid for life. Our aim has always been a final outcome in which the patient is restored to good health without medication or the need for follow-up care more frequently than annual or biennial visits, which are probably indicated for all "normal" adults anyway. The accumulating experience mentioned above, including the reports by Dunn and Chapman,3 and Einhorn,4 have stimulated a reevaluation of dosage in all clinics. In the early years of the availability of 131 I, that is, the 1940's and 1950's, initial doses were often as high as 7 or even 10 mCi, since it was felt desirable to deliver approximately 10,000 to 15,000 rads to the gland. Indeed, a formula occasionally used is as follows: 131 1 D

. C' _ Estimated weight of gland in gm x 10 ose In m 1 24 h our t h yrOl. d upta k e 'In per cent

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This formula in turn may be derived from an assumed "effective halflife" of 5 days for the isotope 131 I in the average toxic thyroid gland. This formula is given in a recent textbook in the field. 6 The present author used essentially this formula a few decades ago with what seemed reasonably good results at the time-approximately two thirds of the cases made euthyroid with a single dose and an incidence of permanent hypothyroidism of only 4 per cent at the end of 3 years. It should be emphasized that the series of approximately 200 thyrotoxic patients treated with radioactive iodine by this author (unpublished) never received a second dose, usually, until at least 6 months after the first and the author tended to shave the dose to the low side since private patients in those days were being charged $5 per millicurie. Subsequent follow-up invariably shows a mounting incidence of late insidious hypothyroidism whenever a "cure rate" as high as two thirds is achieved with a single dose, and this has been borne out by subsequent follow-up of the author's 200 patients (unpublished). The present aim of the author (and most clinics) is to achieve euthyroidism with the initial dose of 131 I in not more than 40 or 50 per cent, indeed, euthyroidism in one third would not constitute an undesirable objective. An early evaluation of a lower dosage range has recently been reported.5 In our own hands the mean initial dose, never very large, has been reduced further. The above noted formula had been abandoned more than 15 years ago. If one were to use it today the "10" would probably have to be replaced by "3." Most of the doses prescribed by the present author nowadays range from 2 to 4 mCi with a small minority of doses as high as 4.5 or 5.0 mCi. Although the formula is not used literally, consideration is given to the uptake value and to the estimated gland weight, which can probably be made to within approximately 15 per cent of the correct weight as determined by subsequent subtotal (90 per cent) thyroidectomy.

REFERENCES 1. Chapman, E. M.: Which Radioiodide? New Eng. J. Med., 285:1142, 1971. '2. Dobyns, B. M., Sheline, G. E., Workman, J. B., et al.: Malignant and benign neoplasms of the thyroid in patients treated for hyperthyroidism: A report of the cooperative Thyrotoxicosis Therapy Follow-up Study. J. Clin. Endocrin. Metab., 38:976,1974. 3. Dunn, J. T., and Chapman, E. M.: Rising incidence of hypothyroidism after radioactive iodine therapy in thyrotoxicosis. New Eng. J. Med., 271 :1037,1964. 4. Einhorn, J., and Wicklund, H.: HypothyrOidism following I:l1 I treatment for hyperthyroidism. J. Clin. Endocrinol. Metab., 26:33, 1966. 5. Hagen, G. A., Ouellette, R. P., and Chapman, E. M.: Comparison of high and low dosage levels of 131 1 in the treatment of thyrotoxicosis. New Eng. J. Med., 227:559,1967. 6. Means, J. H., DeGroot, L. J., and Stanbury, J. B.: In The Thyroid and Its Diseases. New York, McGraw-Hill Book Co., 3rd ed., 1963, p. 226. 7. Sterling, K.: Diagnosis and Treatment of Thyroid Diseases. Cleveland, Ohio, CKC Press, Inc. 1975. Bronx Veterans Administration Hospital 130 West Kingsbridge Road Bronx, New York 10468

Radioactive iodine therapy.

Symposium on Current Concepts of Thyroid Disease Radioactive Iodine Therapy Kenneth Sterling, M.D.* Radioactive iodine has been in use since the pio...
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