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Radioiodine Therapy for Multinodular Toxic Goiter

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Radioiodine Therapy for Multinodular Toxic Goiter ORIGINAL INVESTIGATION Radioiodine Therapy for Multinodular Toxic Goiter Birte Nygaard, MD, PhD; Laszlo Hegedu¨s, MD, PhD; Peter Ulriksen, MD; Kamilla Gerhard Nielsen, MD; Jens Mølholm Hansen, MD Background: Radiolabeled iodine 131 therapy is used reduction in median thyroid volume from 56 mL (range, for treatment of multinodular toxic goiter, but long- 21-430 mL) to 44 mL (range, 15-108 mL), representing a term follow-up studies are lacking. 24% reduction related to the insufficient 131I dose. In all patients, the initial median thyroid volume of 44 mL (range, Methods: A prospective study of 130 consecutive 16-430 mL) decreased to 25 mL (range, 8-120 mL) patients (115 women) treated with 131I for multinodular (P,.005), representing a median reduction of 43%, 24 toxic goiter and followed by evaluation of thyroid vol- months after the last 131I dose. Hypothyroidism evaluated ume (determined using ultrasound) and thyroid func- using life-table analysis developed in 6% of patients who tion variables. did not receive antithyroid pretreatment and 20% who did (P,.005) after a median of 42 months (range, 3-60 Results: The patients were observed for a median of 72 months), the total hypothyroidism frequency being 14% months (range, 12-180 months). Sixty-six patients re- within 5 years of treatment. ceived antithyroid drug pretreatment; 64 did not. Iodine 131 treatment (3.7 MBq/g thyroid tissue corrected to a Conclusions: Ninety-two percent of patients with mul- 100% 24-hour 131I uptake) was given as a single dose in tinodular toxic goiter were cured with 1 or 2 treat- 81 patients, 2 doses in 38, and 3 to 5 doses in 11. One or ments. The thyroid volume was reduced by 43%, with 2 treatments cured 119 patients (92%), and 68 (52%) be- few side effects. Iodine 131 should be the choice of treat- came euthyroid within 3 months after 1 131I treatment. The ment in patients with multinodular toxic goiter. median 131I dose was 370 MBq (range, 93-1850 MBq). Forty-nine patients needing more than 1 131I dose had a Arch Intern Med. 1999;159:1364-1368 ULTINODULAR goiter is a We therefore wanted to evaluate the common cause of hy- long-term changes in thyroid function and perthyroidism, espe- volume using a precise and accurate ul- cially in areas of mild to trasonic technique18 in a large, prospec- moderate iodine defi- tive group of consecutive patients with ciency.1 In these patients, hyperthyroid- multinodular toxic goiter treated with 131I. M 131 ism cannot be expected to be permanently We used an algorithm for I dose calcu- cured by antithyroid drug treatment. Ra- lation, taking volume and 24-hour 131I up- diolabeled iodine 131 therapy is in prin- take into consideration. ciple an attractive treatment modality, since the suppressed extranodular thyroid tis- RESULTS sue is partly protected, and in recent years, the popularity of this treatment has in- Clinical data for the 130 patients are given creased. Therefore, it is of great impor- in Table 1. The median follow-up was 72 tance to evaluate the long-term effects and months (12-180 months). Patients pre- possible side effects of this treatment. A treated with antithyroid drugs did not dif- 1-year follow-up of 70 patients was pub- fer significantly from those not receiving lished from our department in 1986, dem- antithyroid pretreatment with regard to onstrating a 35% reduction of thyroid vol- age, sex, 131I dose, follow-up, or the pro- ume, and hypothyroidism developed in only portion needing more than 1 131I dose. The 1 patient.2 Studies evaluating the long- patients receiving antithyroid pretreat- 131 term effects of I treatment in patients with ment had significantly lower FT4I and FT3I Graves disease,3-7 autonomously function- at the time of 131I treatment than patients From the Departments of ing solitary hot or toxic thyroid nod- not receiving antithyroid pretreatment Endocrinology and Ultrasound, ules,8-12 and multinodular nontoxic goiter (Table 1). Thyroid function variables be- Herlev Hospital, University of have been performed.13-16 However, few fore antithyroid pretreatment were not Copenhagen, Herlev studies6,7,17 have described the long-term ef- available in all patients and are therefore (Drs Nygaard, Ulriksen, 131 Nielsen, and Hansen); and fects of I treatment in patients with mul- not given. The pretreated group had a sig- 131 Endocrinology, Odense tinodular toxic goiter, and a precise evalu- nificantly higher 24-hour I uptake (Table University Hospital, Odense ation of the long-term changes in thyroid 1). The median initial thyroid volume was (Dr Hegedu¨s), Denmark. volume is not available. higher in the pretreated group (59 mL [16- ARCH INTERN MED/ VOL 159, JUNE 28, 1999 1364 ©1999 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 PATIENTS AND METHODS corrected to 100% uptake of 131I after 24 hours. The maxi- mum single dose given was 740 MBq. Serum concentrations of T4 (reference range, 56-129 The study population consisted of 130 consecutive pa- nmol/L [4-10 µg/dL]) and T3 (reference range, 1.0-2.5 131 tients treated with I for a multinodular toxic goiter and nmol/L) and T3 resin uptake (reference range, 0.80-1.25 observed for a minimum of 1 year. Sixty-six patients were arbitrary units) were determined using in-house methods pretreated with antithyroid drugs, whereas 64 were not. An- (assay variation was 6%, 10%, and 5%, respectively). The other 15 patients were treated in this period but were FT4I (reference range, 62-158 arbitrary units) and FT3I unavailable for follow-up within 12 months (7 were given (reference range, 0.8-2.8 arbitrary units) were calculated antithyroid pretreatment). The patients were seen from No- as the total hormone concentration times the T3 resin vember 1, 1979, through April 31, 1994. Type of thyroid uptake. Serum concentrations of thyrotropin were deter- gland was determined using technetium Tc 99m– mined using different commercial assays as described pertechnetate scintigraphy and ultrasound, whereas the previously.3 Ultrasonic scanning and calculation of total diagnosis of hyperthyroidism was based on the clinical pic- thyroid volume (reference range, 9.6-27.6 mL) was per- 18 ture, elevated free triiodothyronine (T3) index (FT3I) and/or formed as previously described using a compound scan- free thyroxine (T4) index (FT4I), and suppressed serum thy- ner (type 3401 and type 1846; Bru¨ el and Kjær, Nærum, rotropin level. Denmark). Sixty-six patients received antithyroid drugs before 131I Thyroid function variables and the size of the thyroid treatment (propylthiouracil [n = 54], methimazole [n = 8], on ultrasonography were determined before and 3⁄4,11⁄2, and carbimazole [n = 4]). In these patients, antithyroid drug 3, 6, and 12 months after treatment, and thereafter, once treatment was discontinued 5 days before 131I therapy and every year. In patients becoming hypothyroid, no further not resumed after 131I treatment. Sixty-four patients did not volume or thyroid function data were included in the data receive antithyroid pretreatment. Pretreatment was based evaluation after hypothyroidism was diagnosed. on the degree of hyperthyroidism and the clinical status of Results are given as median and range or 25th and 75th the patients. percentiles. When percentage of change in thyroid vol- Permanent hypothyroidism was defined as decreased ume is used, the median values of the individual changes FT4I accompanied by an elevated serum thyrotropin con- are given. For statistical evaluation, Wilcoxon test for paired 2 centration. Euthyroidism was defined as FT4I and FT3I design, Mann-Whitney test for unpaired design, x test, and within the reference range. The 131I dose was calculated as life-table analysis were used. The level of significance was 3.7 MBq/g total thyroid mass (evaluated using ultrasound), chosen as P,.05. Table 1. Clinical Data in Patients With Multinodular Toxic Goiter Treated With Iodine 131* Patients Receiving Patients Not Receiving Antithyroid Drug Pretreatment Antithyroid Drug Pretreatment (n = 66) (n = 64) P Age, y 65 (31-81) 64 (41-85) .92 No. of men/women 10/56 5/59 .14 FT4I, arbitrary units 84 (33-253) 179 (124-441) ,.005 FT3I, arbitrary units 2.0 (0.7-5.0) 4.0 (1.5-12.4) ,.005 Thyroid volume, mL 59 (16-430) 43 (18-125) .09 Initial 131I dose, MBq 290 (93-925) 315 (111-740) .97 24-h 131I uptake, % 57 (13-86) 45 (28-76) ,.005 Total 131I dose, MBq 370 (93-1850) 385 (130-1547) .82 No. of 131I doses 14140 21919..99 3-5 6 5 *FT4I indicates free thyroxine index; FT3I, free triiodothyronine index. Unless otherwise indicated, data are given as median (range). 430 mL] vs 43 mL [18-125 mL]), but the difference was The median time to become euthyroid after 131I therapy not significant (P = .09; Table 1). However, comparing was 5 weeks (range, 3 weeks to 24 months) after the last the initial volume in patients needing more than 1 131I 131I treatment (Table 2). There were no significant dif- dose, a highly significant difference was seen (74 mL [21- ferences between patients given antithyroid pretreatment 430 mL] in the pretreated group vs 47 mL [23-125 mL] and those who were not. Sixty-eight patients (52%) were in the group not pretreated) (P,.005). euthyroid within 3 months after the first 131I treatment. Eight The median initial 131I dose was 313 MBq (93-925 patients did not become euthyroid after 131I treatment. Three MBq), whereas the median total dose was 370 MBq (93- of these 8 patients had 1 131I treatment, 4 patients had 2 1850 MBq). More than 1 dose was given due to persis- treatments, and 1 patient had 3 treatments.
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