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      The effect of prior antithyroid drug use on delaying remission in high uptake Graves' disease following radioiodine ablation

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          Abstract

          Antithyroid drugs (ATDs) have been shown to attenuate the effectiveness of radioiodine (radioiodine ablation, RIA) therapy in Graves' disease. We undertook a study to look at the impact of iodine uptakes on the outcome of 131I therapy. To determine the effect of prior ATD use on the duration of time to achieve cure in patients with high vs intermediate uptake Graves' disease who received a fixed dose (15 mCi) of 131I radioiodine. In a retrospective study of patients with Graves' disease, 475 patients who underwent RIA were followed-up on a two-monthly basis with thyroid function tests. Of the 123 patients with a documented preablation RAIU and consistent follow-up it was observed that 40 patients had an intermediate RAIU (10–30%) and 83 subjects had a distinctly increased uptake (>30%). Successful cure was defined as the elimination of thyrotoxicosis in the form of low free thyroxin and rising TSH levels. When a standard dose of 15 mCi 131I was administered, a cure rate of 93% was achieved. The median duration of time to cure (TC) was 129 days. Surprisingly, a direct proportional linear relationship ( R 2=0.92) was established between time to cure and radioiodine uptake (TC > 3 0%=172days, TC 10 3 0%=105 days, P<0.001). Patients who used ATD medications took a proportionately longer duration to achieve remission (TC NO ATD=102days, TC ATD=253days, P<0.001). The effect of prior ATD therapy in delaying remission was amplified in the subset of patients with higher uptakes (TC > 3 0% + ATD=310days, TC > 3 0% + NO ATD=102days, P<0.001) compared to those with the intermediate uptakes (TC 10 3 0% + ATD=126 days, TC 10 3 0% + NO ATD=99 days, P<0.001). RIA, using a dose of 15 mCi achieved a high cure rate. Higher uptakes predicted longer time to achieve remission, with prior ATD use amplifying this effect.

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          Most cited references33

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          Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists.

          Thyrotoxicosis has multiple etiologies, manifestations, and potential therapies. Appropriate treatment requires an accurate diagnosis and is influenced by coexisting medical conditions and patient preference. This article describes evidence-based clinical guidelines for the management of thyrotoxicosis that would be useful to generalist and subspeciality physicians and others providing care for patients with this condition. The development of these guidelines was commissioned by the American Thyroid Association in association with the American Association of Clinical Endocrinologists. The American Thyroid Association and American Association of Clinical Endocrinologists assembled a task force of expert clinicians who authored this report. The task force examined relevant literature using a systematic PubMed search supplemented with additional published materials. An evidence-based medicine approach that incorporated the knowledge and experience of the panel was used to develop the text and a series of specific recommendations. The strength of the recommendations and the quality of evidence supporting each was rated according to the approach recommended by the Grading of Recommendations, Assessment, Development, and Evaluation Group. Clinical topics addressed include the initial evaluation and management of thyrotoxicosis; management of Graves' hyperthyroidism using radioactive iodine, antithyroid drugs, or surgery; management of toxic multinodular goiter or toxic adenoma using radioactive iodine or surgery; Graves' disease in children, adolescents, or pregnant patients; subclinical hyperthyroidism; hyperthyroidism in patients with Graves' ophthalmopathy; and management of other miscellaneous causes of thyrotoxicosis. One hundred evidence-based recommendations were developed to aid in the care of patients with thyrotoxicosis and to share what the task force believes is current, rational, and optimal medical practice.
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            A randomized comparison of radioiodine doses in Graves' hyperthyroidism.

            The optimal method for determining iodine-131 treatment doses for Graves' hyperthyroidism is unknown, and techniques have varied from a fixed dose to more elaborate calculations based upon gland size, iodine uptake, and iodine turnover. Patients with Graves' hyperthyroidism (n = 88) who had not been previously treated with radioactive iodine were randomized to one of four dose calculation methods: low-fixed, 235 MBq; high-fixed, 350 MBq; low-adjusted, 2.96 MBq (80 micro Ci)/g thyroid adjusted for 24 h radioiodine uptake; and high-adjusted, 4.44 MBq (120 micro Ci)/g thyroid adjusted for 24 h radioiodine uptake. Subjects were followed for mean of 63 months (range, 10-94 months) for the following clinical outcomes: euthyroid without medication, hyperthyroid requiring further radioiodine, and hypothyroid requiring life-long L-T(4). Mean treatment doses were similar in the different outcome groups. We could not demonstrate any advantage to using an adjusted dose method. Survival analysis did not demonstrate any difference in the time to outcome between the fixed and adjusted dose methods. The use of a fixed dose method simplifies the approach to treatment with potential cost savings.
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              The effect of methimazole pretreatment on the efficacy of radioactive iodine therapy in Graves' hyperthyroidism: one-year follow-up of a prospective, randomized study.

              The effect of antithyroid drugs on the efficacy of radioiodine (131I) treatment is still controversial. This study evaluated the effect of methimazole pretreatment on the efficacy of 131I therapy in Graves' hyperthyroidism. Sixty-one untreated patients were randomly assigned to receive 131I alone (32 patients) or 131I plus pretreatment with methimazole (30 mg/d; 29 patients). 131I was administered 4 d after drug discontinuation. The calculated 131I dose was 200 microCi/g thyroid tissue as estimated by ultrasound, corrected by 24-h radioiodine uptake. Serum TSH, T4, and free T4 were measured 4 d before 131I therapy, on the day of treatment, and then monthly for 1 yr. Considering cure as euthyroidism or hypothyroidism, based on free T4 measurement, approximately 80% of patients from both groups were cured 3 months after beginning 131I treatment. After 1 yr the groups were similar in terms of persistent hyperthyroidism (15.6% vs. 13.8%), euthyroidism (28.1% vs. 31.0%), or hypothyroidism (56.3% vs. 55.2%). Relapsed patients presented larger thyroid volume (P = 0.002), higher 24-h radioiodine uptake (P = 0.022), and T3 levels (P = 0.002). Multiple logistic regression analysis identified T3 values as an independent predictor of therapy failure. In conclusion, pretreatment with methimazole had no effect on either the time required for cure or the 1-yr success rate of 131I therapy.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                15 January 2016
                1 January 2016
                : 5
                : 1
                : 34-40
                Affiliations
                [1 ]Department of General Medicine, Sri Ramachandra University , 1 Ramachandra Nagar, Porur, Chennai, 600116, India
                [2 ]TB and Pulmonary Medicine, Sri Ramachandra University , 1 Ramachandra Nagar, Porur, Chennai, 600116, India
                [3 ]Endocrinology, Diabetes and Metabolism, Sri Ramachandra University , 1 Ramachandra Nagar, Porur, Chennai, 600116, India
                Author notes
                Correspondence should be addressed to K G Seshadri Email: krishnagseshadri@ 123456gmail.com
                Article
                EC150119
                10.1530/EC-15-0119
                4738237
                26772754
                c73e6d57-1836-40cf-b86b-6393629f2f3f
                © 2016 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 17 December 2015
                : 15 January 2016
                Categories
                Research

                131i radioiodine ablation,graves' disease,antithyroid drug pretreatment,24-hour radioiodine uptake,remission in graves' disease

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