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Predictors of Autoimmune Hyperthyroidism Relapse in Children after Discontinuation of Antithyroid Drug Treatment

Clinical Epidemiology Unit (F.K., C.A.), Institut National de la Santé et de la Recherche Médicale CIE5 (F.K., C.A), and Department of Pediatric Endocrinology (M.C., M.-A.G., P.C., J.L.), Centre de Référence Maladies Endocriniennes de la Croissance, Institut National de la Santé et de la Recherche Médicale U690 (M.C., M.-A.G., P.C., J.L.), Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Université Paris VII, 75019 Paris, France

Address all correspondence and requests for reprints to: Juliane Léger, M.D., Department of Pediatric Endocrinology, Centre de Référence Maladies Endocriniennes de la Croissance, Institut National de la Santé et de la Recherche Médicale U690, Hôpital Robert Debré, 48 Bd Sérurier, 75019 Paris, France. E-mail: juliane.leger{at}rdb.aphp.fr.

Context: There is debate about how Graves’ disease (GD) should be treated in children.

Objective: The aim of this study was to identify predictors of relapse after antithyroid drug (ATD) treatment in children with GD.

Study Design and Setting: 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.

Results: 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 T₄ (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%.

Conclusions: 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.