RADIOJODINE THERAPY OF THYROTOXICOSIS. By G. L. JACKSON, M.D.*

Transcription

1 AUGUST, 97 RADIOJODINE THERAPY THYROTOXICOSIS By G. L. JACKSON, M.D.* HARRISBURG, T HERE has been considerable discussion concerning the frequency and delayed onset of hypothyroidism after treatment of thyrotoxicosis Wi th radioiodine. Although the use of 3 has been regarded as a safe, reliable, and convenient method of treatment, the incidence of hypothyroidism has detracted from its uniform acceptance. Because of this, and because we have used low dose J3 therapy for a number of years to treat thyrotoxicosis, it seemed appropriate to review our series to evaluate its effectiveness and the incidence of hypothyroidism. In this report the patients were identified according to important characteristics. The significance of these characteristics in predicting a hypothyroid result will be discussed. METHOD The charts of all patients treated with radioiodine for thyrotoxicosis from 963 to September 30, 969 were reviewed. The patients were classified by the following: (a) sex; (b) age; (c) number of doses; (d) total dose administered; (e) weight of gland, estimated on the basis of physical findings by one of the observers (GLj) ; (f) dose delivered, the calculation of which was based upon Quimby s8 formula: 90 X jc (deposited in the gland)* rads=.. grams (estlmated weight ofthe gland) and (g) evaluation of result of therapy. The patients were referred to the Section of Nuclear Medicine for complete care of thyrotoxicosis. Each patient was followed closely and seen at regular intervals, generallv I, 2, 3, 6 months and yearly after treatment. Each was evaluated, where p05- * c administered X uptake of therapeutic dose PENNSYLVANIA sible, on the basis of 3 factors (2 of which are quantitative). These 3 factors are: I. The J3 uptake at 4 and 24 hours at least 3 months after the last treatment. An uptake ofless than 0 per cent is considered in the hypothyroid range.7 An uptake greater than 45 per cent is considered to be in the hyperthyroid range. 2. Chemical determination of circulating thyroid substances.t A protein bound iodine determination below 4.0 gamma per cent is considered to be in the hypothyroid range; above 8.o gamma per cent is in the hyperthyroid range. A T-4 by column chromatography less than 2.9 gamma per cent is in the hypothyroid range; greater than 6.4 gamma per cent is in the hyperthyroid range. 3. A clinical evaluation based upon significant symptoms and physical findings; e.g., weight, temperature, pulse rate, pulse pressure, presence of a fine tremor, eye signs and symptoms, skin and hair texture, sweating, thyroid size, presence of a bruit, deep tendon reflexes, temperature intolerance, fatigue, nervousness, muscle aches, the patient s evaluation of his/her condition, and the referring physician s evaluation. \Vhere all 3 of these factors (3 uptake, blood chemistry, clinical evalu ation) were in the same direction, a final diagnosis was easy. When this was not the case, the final evaluation was based upon the consistent majority. RESULTS One hundred and forty-eight patients were treated during this interval. There are ii8 females (8o per cent) and 30 males. t Majority performed at BioScience.ahoratories, Van Nuys, California. * Head, Section of Nuclear Medicine, Harrisburg Hospital, Harrisburg, Pennsylvania; Clinical Associate Professor of Medicine, Pennsylvania State University. 726

2 VoL. 2, Radioiodine Therapy of Thyrotoxicosis 727 One hundred and thirty-one patients have been followed for a total of 252 patient years. Of these, io females (8o per cent) and 26 males are included in the 3 patients followed for 3 months or more. The mean period of follow-up is i.92 years and the median follow-up is 2 years. The number of patients followed by interval is seen in Table I. Twelve patients were in the age group years at the time of treatment; 32 from 30-39; 36 from 40-49; 37 from 50-59; I 6 from ; and I 5 were 70 or more years of age (Fig. i). One hundred and nine patients ( u.per cent) received only i dose; 24 received 2 doses; I 2 received 3 doses; 2 required 4 doses; and I patient has received doses (Fig. 2). The total dose administered was: -3.0 mc in 25 patients; mc in 67 (.5 per cent); 4.5.O mc in 8; 5.i-6.o mc in 4; mc in 5; mc in 8; 8.i-.o mc in I ; mc in 7; 0.-I 5 mc in 7; and more than 5 mc in 6. In 3 patients the weight of the gland was estimated to be less than 30 gm. In 74 patients (5o per cent) the weight ranged from 3-59 gm.; in 30 from gm.; and in 3 the weight exceeded 8o gm. The total dose delivered to the thyroid Follow-up (yr.) Patients of TABLE RESULTS RADIOIODINE THERAPY was calculated to be less than 3,500 rads in I 5 patients (8 of whom were judged finally to be euthyroid, 3 finally judged hyperthyroid, I finally judged to be hypothyroid, 3 no follow-up). Sixty-eight patients (47 per cent) received from 3,500-6,999 rads (48 ofwhom were finally judged to be euthyroid, 7 finally judged hypothyroid, 3 no follow-up). Thirty-five received from 7,000-0,000 rads; and 23 received more than 0,000 rads. Of the 8 patients who received more than 7,000 rads, 9 were finally judged euthyroid, 7 finally judged hypothyroid, and 2 finally judged hyperthyroid. In 7 patients this calculation could not be performed: all were finally judged eu thyroid. The results of therapy evaluated according to the procedure previously outlined are shown in Table II. These 48 patients include all of those treated. Seventeen have not been followed for 3 months. This is not sufficiently long for follow-up evaluation. The remaining patients (3) have been followed from 3 months tohmore than years after the last treatment dose (Table i). It should be noted (Table ii) that 27 (96 per cent) of the patients were cured of thyrotoxicosis. Fifteen patients (i i per cent) of the series became hypothyroid. I Euthyroid Hyperthyroid Hypothyroid JO JO 8.6 I JO I 0

3 728 G. L. Jackson AUGUST, NO. PATIENTS YEARS AGE FIG. I. Ages of 48 patients treated with radiolodine for thyrotoxicosis. The hypothyroid patients were tabulated according to the various subsets (Table III). From Table III the following significant observations are noted: TABLE NO. ITIENTS I I0 RESULTS RADIOIODINE THERAPY FOR THYROTOXICOSIS II J3 Uptake PBI or T4 Clinical Final Evaluation HypothyroidRange II 4 II 5 II EuthyroidRange Hyperthyroid Range I0 #{49} 26% I NO. DOSES FIG. 2. Number of treatment doses of radioiodine administered to 48 patients. I. No patient received more than 7 mc. 2. The majority (3 of 5=87 per cent) had i treatment. 3. The estimated weight of thyroid glands was 6 gm. or less. 4. The delivered dose exceeded 3,500 rads in 4 of the ic patients. No Follow-up Data

4 \OL. 2, Radioiodine Therapy of Thyrotoxicosis 729 TABLE III RADIOIODIN E INDUCED HYPOTHYROIDISM Patient Sex Age of Doses Total (mc) Dose \\ght of Gland (gm.) Dose (rads) Deliverel Onset of Hypo- thyroid- ism (yr.) Treatment Uptake (per cent) 8 38 i , () 7 o I ,9oo 23! F ,7oo 370 F 5 I ,6oo 429 l 7 I , M ,00 I F 53 I , F 3 I ,200 4I 75 i8o8 M 52 I , F 36 I , F 6i I , M , M 42 I ,6oo 2204 F I , oo F I 3.0 6o 2, The onset of hypothyroidism (elapsed interval since treatment administered) was /4 year or less in io patients; /3 year in I patient; /2 year in 2; I year in 2; and years in I (Fig. 4). DISCUSSION In 964 we reported our experience with a group of 8i patients treated with low dose radioiodine and studied during the preceding 6 years.4 The procedures were similar to those reported in this series. In the 964 report, 6 patients became hypothyroid (8.5 per cent). The onset of hypothyroidism was usually early (within 6 months after therapy). Few patients became hypothyroid as a late cornplication. These findings also are similar to those reported here. Table ii demonstrates that the bias introduced by the clinical evaluation bears a direct relationship to the final evaluation. We have tried to make the clinical evaluations as unbiased as possible, but recognize that some is introduced. If one made a final evaluation based upon the J3 uptake, 9 patients would be considered hypothyroid. As is well known, the JH uptake is not a good determinant of the hypothyroid state.5 On the other hand, the chemical 74

5 730 Cl. L. Jackson AUGUSI, 97 measures of hypothyroidism would have placed 3 of our subjects in the hypothyroid category. If one examines the hvperthyroid group as identified by J3 studies, there would be 7 in this category. The chemical evaluation would have listed 28 as hyperthyroid. It thus seems that strict adherence to either the uptake or chemical determination would introduce a distortion. In fact, then, we believe that this 3 part evaluation has more safeguards than bias. It also reflects our opinion of the significance of clinical judgment. It should be noted (Fig. 3) that the median total dose of J3 administered is less than mc. \Vhen compared with other reports in the literature3 6 9 this is found to be quite low. Similarly, the incidence of hypothyroidism is lower than that frequently reported.2 A recently published exception NO. PATIENTS is the prospective studs- of Smith and \Vilson.#{76}The report 8 per cent of patients receiving a conventional dose oft3 (i.e., 40 sc/gm. of thyroid, delivering about 7,000 rads, 3-7 mc range) became h poth roid in the first year. Twenty-nine per cent became hvpothroid in years. For patients receiving a half-dose ( o,.c/gm. of thyroid, delivering about 3,500 rads, mc range) the hypothyroid result is 4 per cent at the end of I year and 7 per cent at 5 ears. Our results fall between the conventional and half-dose group of Smith and \Vilson as seen in Figure. Their conventional and half-dose curve plotted in a similar manner is superimposed. The derivation of this curve is shown in Table I. The annual increment of hypothyroidism seen with conventional doses of radioiodine is not seen in the series reported here mci ADMINISTERED G. 3. Total treatment dose of radioiodine (in millicuries) administered to 48 patients.

6 VOL. 2, Radioiodine Therapy of Thyrotoxicosis 73 NUMBER PATiENTS 4 5 YEARS FIG. 4. Onset of hypothyroidism according to interval from last 3 treatment. Disadvantages accompany the lowered incidence of hypothyroidism reported. Repeat doses of I are required to control hyperthyroidism. Twenty-six per cent of our patients required a second or more treatment doses. Delayed control of hyperthyroid symptoms may be offset by the administration of antithyroid drugs beginning 7 days after J3 therapy. When anti thyroid drugs (propylthiou racil or methimazole) or goitrogen blocking agents (T-4 or T_3) were utilized, they were discontinued at the second month after radioiodine therapy. No patients received any thyroid-active drugs at the time of the 3 month postiodine uptake. In general, all thyroid-active agents have been discontinued 4 weeks before the 3 month evaluation. SUMMARY A review of the Harrisburg Hospital experience in treatment of hyperthyroidism with low administered doses of P3 is presented. The incidence of hypothyroidism is I I per cent. Hypothyroidism was most frequently diagnosed within months of treatment. Three per cent of patients remain hyperthyroid. It is presumed that additional I s in this group will result in a satisfactory clinical result. 0/ f ( IC INODENcE HYPOTHYROIDISM / 5-, YEARS AFTER Rx S 5-. Smlth&WIIscn.8MJ (ccnvsntlonol do.,) 5-.. Sinith&WIho.,SMJ : (half doss) G. 5. Comparative incidence of hypothyroidism. Department of Radiology Section of Nuclear Medicine Harrisburg Hospital South Front Street Harrisburg, Pennsylvania 70 REFERENCES 5-. Hmrlsbusq Hos S*Iss I. DUNN, J. T., and CHAPMAN, E. M. Rising mcidence of hypothyroidism after radioactive iodine therapy in thyrotoxicosis. New Eng/and 7. Med., 964, 27!, Editorial. New look at radioiodine therapy of thyrotoxicosis. New Eng/and 7. Med., 967, 277, HAMBURGER, J. I., and PAUL, S. When and how to use higher 3-I doses for hyperthyroidism. New Eng/and 7. Med., 968, 279, JACKSON, G. L., and PERNA,. X. Experiences with therapeutic radioiodine, Bull. Harrisburg, Hosp., MEANS, J. H., DEGROOT, L. J., and STAN BURY, J. B. The Thyroid and Its Diseases. McGraw- Hill Book Company, New York, 963, pp NAL, M. M., BEIERwALTES, W. H., and PATNO, M. E. Treatment of hyperthyroidism with sodium iodide il.M.il., 966, 97, PITTMAN, J. A., DAILEY, G. E., III, and BESCHI, R. J. Changing normal values for thyroidal radioiodine uptake. New England 7. Med., 969, 280, QUIMBY, E. R., and FEITELBERG, S. Radioactive Isotopes in Medicine and Biology, Basic Physics and Instrumentation. Lea & Febiger, Philadelphia, 962, pp SILVER, S. Radioactive Nuclides in Medicine and Biology. Lea & Febiger, Philadelphia, 968, pp Jo. SMITH, R. N., and WILSON, G. M. Clinical trial of different doses of 3-I in treatment of thyrotoxicosis. Brit. M. 7., 967, I, I

7 This article has been cited by:. Jashovam Shani, Harold L. Atkins, Walter Wolf Adverse reactions to radiopharmaceuticals. Seminars in Nuclear Medicine 6:3, [CrossRef] 2. George L. Jackson Calculated low dose radio-iodine therapy of thyrotosicosis. International Journal of Nuclear Medicine and Biology 2:2, [CrossRef]