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      Adverse Events Associated with Methimazole Therapy of Graves' Disease in Children

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          Abstract

          Objective. Graves' disease is the most common cause of hyperthyroidism in the pediatric population. Antithyroid medications used in children and adults include propylthiouracil (PTU) and methimazole (MMI). At our center we have routinely used MMI for Graves' disease therapy. Our goals are to provide insights into adverse events that can be associated with MMI use. Methods. We reviewed the adverse events associated with MMI use in our last one hundred consecutive pediatric patients treated with this medication. Results. The range in the patient age was 3.5 to 18 years. The patients were treated with an average daily dose of MMI of 0.3±0.2 mg/kg/day. Adverse events attributed to the use of the medication were seen in 19 patients at 17±7 weeks of therapy. The most common side effects included pruritus and hives, which were seen in 8 patients. Three patients developed diffuse arthralgia and joint pain. Two patients developed neutropenia. Three patients developed Stevens-Johnson syndrome, requiring hospitalization in 1 child. Cholestatic jaundice was observed in 1 patient. No specific risk-factors for the development of adverse events were identified. Conclusions. MMI use in children is associated with a low but real risk of minor and major side effects.

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          Antithyroid drugs.

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            Predictors of autoimmune hyperthyroidism relapse in children after discontinuation of antithyroid drug treatment.

            There is debate about how Graves' disease (GD) should be treated in children. The aim of this study was to identify predictors of relapse after antithyroid drug (ATD) treatment in children with GD. We conducted a prospective, multicenter cohort study of children (n = 154) with GD treated with carbimazole for an intended duration of 24 +/- 3 months. After the end of treatment, patients were followed up for at least 2 yr. The primary outcome was hyperthyroidism relapse. Cox's regression analysis was used and a prognostic score was constructed. The overall estimated relapse rate for hyperthyroidism was 59% (95% confidence interval 52-67%) at 1 yr and 68% (95% confidence interval 60-76%) at 2 yr after the end of treatment. Multivariate survival analysis showed that the risk of relapse was higher for patients of non-Caucasian origin [hazard ratio (HR) = 2.54, P < 0.001], with high serum thyroid-stimulating hormone receptor antibodies (HR = 1.21 by 10 U, P = 0.03) and free T(4) (HR = 1.18 by 10 pmol/liter, P = 0.001) levels at diagnosis. Conversely, relapse risk decreased with increasing age at onset (HR = 0.74 per 5 yr, P = 0.03) and duration of first course of ATD (HR = 0.57 per 12 months, P = 0.005). A prognostic score was constructed, allowing the identification of three different risk groups, with 2-yr relapse rates of 46, 77, and 98%. A longer initial duration of euthyroid state with ATD seems to be the only variable related to the risk of hyperthyroidism relapse in children that can be manipulated. Ethnic origin, age, and severity of the disease at diagnosis may guide long-term disease management decisions.
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              Putting propylthiouracil in perspective.

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                Author and article information

                Journal
                Int J Pediatr Endocrinol
                IJPE
                International Journal of Pediatric Endocrinology
                Hindawi Publishing Corporation
                1687-9848
                1687-9856
                2010
                7 March 2010
                : 2010
                : 176970
                Affiliations
                Department of Pediatrics, Yale Child Health Research Center, 464 Congress Avenue, Room 237, New Haven, CT 06520, USA
                Author notes

                Academic Editor: Dennis M. Styne

                Article
                10.1155/2010/176970
                2833412
                20224800
                b3f09869-a5ea-4aee-86fb-3baf55c39fa9
                Copyright © 2010 Scott A. Rivkees et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 30 November 2009
                : 12 January 2010
                : 1 February 2010
                Categories
                Clinical Study

                Pediatrics
                Pediatrics

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