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Effect of antithyroid drugs on radioiodine treatment: risk of ophthalmopathy should not be ignored in Graves’ disease
- Shamasunder H Acharya, Alison Avenell, Sam Philip, John S Bevan and Prakash Abraham (3 March 2007)
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Reduction in efficacy of radioiodine treatment within a week of antithyroid drug therapy may be due to radio-resistance induction.
- Jolanta U Weaver, Salman Razvi. (11 March 2007)
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Antithyroid Drugs and Radioiodine Therapy
- Sameer Chadha, Shikha Mehta, Medical Student , Maulana Azad Medical College, New Delhi ,India (13 March 2007)
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Importance of calculation of absorbed dose in radioiodine treatment in patients pre-treated with antithyroid drugs
- Gertrud Berg (12 October 2007)
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Shamasunder H Acharya, Specialist Registrar Department of Endocrinology, Aberdeen Royal Infirmary, Aberdeen, AB25 2ZN, Alison Avenell, Sam Philip, John S Bevan and Prakash Abraham
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In the recent systematic review by Walter et al(1), adjunctive antithyroid drugs have been shown to increase the risk of treatment failure, when used along with radioiodine therapy. Graves’ ophthalmopathy occurs in 25-50% of patients with Graves’ disease and in a sizeable minority, Graves’ ophthalmopathy is an unpleasant, painful and even sight threatening condition(2). Although controversial, strong evidence suggests that radioiodine therapy can exacerbate thyroid eye disease(3). We were surprised to note that there was no mention of ophthalmopathy as an adverse event in this review, although the authors discuss occurrences such as atrial fibrillation. Significant proportions of patients had evidence of ophthalmopathy and were given prophylactic steroids to prevent worsening of eye disease in four randomised controlled trials in this review. Two of the randomised controlled trials had described ophthalmopathy outcomes and these deserve separate mention. We are currently undertaking a systematic review of radioiodine therapy and its effects on ophthalmopathy. 1. Walter MA, Briel M, Christ-Crian M, Bonnema SJ, Connell J, Cooper DS et al. Effects of antithyroid drugs on radioiodine treatment: systematic review and meta-analysis of randomised controlled trials. http://www.bmj.com/cgi/rapidpdf/bmj.39114.670150.BEv2 2. Cawood T, Moriarty P, O’Shea D. Recent developments in thyroid eye disease. BMJ 2004; 329:385-90 3. Bartalena L, Marcocci C, Bogazzi F, Manetti L, Tanda ML, Dell’Unto E. et al. Relation between therapy for hyperthyroidism and the course of Graves’ ophthalmopathy. N Engl J Med 1998; 338:73-8 Competing interests: None declared |
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Jolanta U Weaver, Senior Lecturer and consultant physician Department of Endocrinology, Queen Elizabeth Hospital, Gateshead, UK NE9 6SX, Salman Razvi.
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Reduction in efficacy of radioiodine treatment within a week of antithyroid drug therapy may be due to radio-resistance induction. Salman Razvi, specialist registrar 1,2, Jolanta U Weaver, consultant physician and senior lecturer 2,3. j.u.weaver@ncl.ac.uk 1 Department of Endocrinology, South Tyneside District Hospital, South Shields, UK. 2 School of Clinical Medical Sciences, University of Newcastle upon Tyne, Newcastle upon Tyne, UK. 3 Department of Endocrinology, Queen Elizabeth Hospital, Gateshead, UK. We read with interest the meta-analysis performed by Walter and colleagues investigating the influence of antithyroid therapy on outcomes of radioiodine treatment in hyperthyroidism 1. The results of their meta- analysis confirm the very successful outcomes reported by us in our study of more than 200 patients with hyperthyroidism, in which we presented the lowest reported treatment failure (6.5%) for the given dose of 400MBq of radioiodine, with overall 29% euthyroidism and 64% of hypothyroidism at 12 months of follow-up 2. Our study was not a randomised controlled study. We discontinued antithyroid drugs in excess of 2 weeks (16 days) prior to radioiodine treatment. We note that the meta-analysis did not explore the mechanism behind the effect of antithyroid drugs on the outcome of radioiodine treatment. We would suggest that the possible mechanisms for this reduction in efficacy of radioiodine with adjunctive antithyroid therapy within a week either pre or post radioiodine, may be drug induced radio-resistance 3, 4. Clearly, the meta-analysis supports the practice of discontinuing antithyroid drug therapy at least a week prior to radioiodine treatment. Future studies should be designed towards investigating the most appropriate time period of cessation of antithyroid drugs prior to radioiodine therapy. Reference: 1. Walter MA, Briel M, Christ-Crain M, Bonnema SJ, Connell J, Cooper DS, et al. Effects of antithyroid drugs on radioiodine treatment: systematic review and meta-analysis of randomised controlled trials. BMJ 2007; 334:514. 2. Razvi S, Basu A, McIntyre EA, Wahid ST, Bartholomew, PH, Weaver JU. Low failure rate of fixed administered activity of 400 MBq 131I with pre- treatment with carbimazole for thyrotoxicosis: the Gateshead Protocol. Nucl Med Commun. 2004;25(7):675-82. 3. Crooks J, Buchanan WW, Wayne EJ, Macdonald E. Effect of pretreatment with methylthiouracil on results of I-131 therapy. Br Med J. 1960;1(5167):151-4. 4. Sabri O, Zimny M, Schreckenberger M, Reinartz P, Ostwald E, Buell U. Radioiodine therapy in Graves' disease patients with large diffuse goiters treated with or without carbimazole at the time of radioiodine therapy. Thyroid 1999;9(12):1181-8. Competing interests: None declared |
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Sameer Chadha, Medical Student Maulana Azad Medical College, New Delhi, India, Shikha Mehta, Medical Student , Maulana Azad Medical College, New Delhi ,India
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Radioiodine causes progressive destruction of the thyroid cells and is used as initial treatment or for treatment of relapses after a trial of anti-thyroid drugs. The most common indication is hyperthyroidism due to Graves Disease or Toxic Nodular Goiter. The average therapeutic dose is 3-6 m curie with toxic goiter requiring higher doses than Graves disease. The response is slow starts after 2 weeks gradually increases, and peaks at 3 months. Thyroid status is evaluated after 3 months and a repeat dose,if needed is given.
There is a risk of thyrotoxic crisis, which is minimised by pre-treatment with anti-thyroid drugs for a month before the treatment. This antecedent treatment must be considered for all elderly patients or those with cardiac problems to deplete the thyroid stores before administration of radioiodine. Anti-thyroid drugs must be then stopped at least three days before radioiodine administration to achieve optimum iodine uptake.
Competing interests: None declared |
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Gertrud Berg, ass professor Department of Oncology, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden
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There is a disagreement about the influence of antithyroid drugs on radioiodine treatment. In the systematic review and meta-analysis of randomised controlled trials it was concluded that antithyroid drugs increase rates of failure and reduce rate of hypothyroidism if they are given in the week before or after radioiodine treatment (Walter et al 2007). I believe that one explanation for failure is the fact that antithyroid drugs simply affects the uptake and residence time of radioiodine. There is a risk in these cases that the thyroid receives a smaller absorbed dose from radioiodine if dose calculation including estimation of effective half-life of the radioiodine is not performed. If a dose calculation is performed, the outcome will be the same in patients treated with antithyroid drugs as in those without pre-treatment. In Sweden the authorities recommend to use individual dose calculations for radioiodine treatment of patients with hyperthyroidism. We have thus for many years used a protocol where a test dose is given in order to calculate the amount of radioactivity (MBq) needed to obtain the absorbed dose (Gy) aimed at. We have shown that when we aim at an absorbed dose of 120 Gy we only have a failure of 7 % (Berg et al 96 b). The individual dose calculation takes into account the thyroid volume, the iodine uptake after 24 hours and the effective half -life of the radioiodine. We have reported about the special significance of the effective half-life (residence time of the radioisotope) in these measurements (Berg 1996a). We thus showed that the effective half-life can vary between 2 and 8 days where the mean half-life for patients with Graves’ disease was 5.3 days without pre medication with antithyroid drugs whereas patients with medication up to 7 days before treatment had a mean effective half-life of 4.4%. Thus if the half-life is not considered it is likely that the patients with prior antithyroid drugs will receive a lower absorbed dose than prescribed. The shorter period without medication the more impact on the half-life can be expected. One explanation for the reduced half-life is that antithyroid drugs reduce the protein binding of iodine to thyroglobulin at the apical part of the thyrocytes. The radioiodine will thus reside shorter in the gland. We often see a high uptake and a short half-life in patients with prior antithyroid drug treatment. It is our experience however that when an individual dose calculation is performed the treatment failure is in the same order for patients with and without prior medication. If individual dose calculation is not performed and standard activities are used it is likely that patients with prior antithyroid drugs receive a lower absorbed dose to the thyroid than wanted. A dose of eg 90 Gy is simply more unlikely to cure than the aimed dose of 120 Gy. Berg G, Michanek A, Holmberg E, Nyström E. Clinical outcome of radioiodine treatment of hyperthyroidism: a follow up study. J Int Med 1996; 239:165-71. Berg G, Michanek A, Holmberg E, Fink M. Iodine-131 treatment of hyperthyroidism: significance of effective half-life measurements. J Nucl Med 1996; 37: 228-32 Competing interests: None declared |
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