Graves' Disease in Children: Long-term Outcomes of Medical Therapy

Shona Rabon; Amy M. Burton; Perrin C. White

Disclosures

Clin Endocrinol. 2016;85(4):632-635. 

In This Article

Abstract and Introduction

Abstract

Background and objectives Management options are limited for the treatment of Graves' disease, and there is controversy regarding optimal treatment. We describe the demographic and biochemical characteristics of children with Graves' disease and the outcomes of its management.

Methods This is a retrospective study reviewing medical records from 2001 to 2011 at a tertiary-care paediatric hospital. Diagnostic criteria included elevated free T4 and total T3, suppressed TSH, and either positive thyroid-stimulating immunoglobulin or thyroid receptor antibodies or clinical signs suggestive of Graves' disease, for example exophthalmos. Patients were treated with antithyroid drugs (ATD), radioactive iodine, or thyroidectomy. The main outcome measures were remission after medical therapy for at least 6 months and subsequent relapse.

Results A total of 291 children met diagnostic criteria. A total of 62 were male (21%); 117 (40%) were Hispanic, 90 (31%) Caucasian, and 59 (20%) African American. Mean age (±standard deviation) at diagnosis was 12·3 ± 3·8 (range 3–18·5) years. At diagnosis, 268 patients were started on an antithyroid drug and 23 underwent thyroid ablation or thyroidectomy. Fifty-seven (21%) children achieved remission and 16 (28%) of these patients relapsed, almost all within 16 months. Gender and ethnicity did not affect rates of remission or relapse. Of 251 patients treated with methimazole, 53 (21%) had an adverse reaction, including rash, arthralgias, elevated transaminases, or neutropenia.

Conclusions Most children with Graves' disease treated with ATD do not experience remission, but most remissions do not end in relapse. Adverse reactions to methimazole are common but generally mild.

Introduction

Hyperthyroidism in children and adolescents is primarily caused by Graves' disease. As with other autoimmune disorders, Graves' disease is thought to be caused by a complex interaction of genetic and environmental factors.[1]

Most patients diagnosed with Graves' disease are initially treated with antithyroid drugs (ATD). These include propylthiouracil (PTU), methimazole, and carbimazole. Carbimazole is not approved for use in the United States, and PTU is now strongly discouraged in children owing to concern for hepatotoxicity.[1–4] Therefore, most centres in the United States now rely solely on methimazole for medical management of Graves' disease. Adverse reactions of methimazole include rash, pruritus, arthralgias, myalgias, liver dysfunction, and neutropenia. Few large-scale studies have evaluated the prevalence of side effects of methimazole and ultimate outcomes of patients on methimazole, but it is estimated that up to 25% of children will have a reaction on methimazole.[1,5,6] Patients with hyperthyroidism who do not respond to medical therapy or who have adverse reactions to ATDs must choose alternate therapy such as radioactive iodine thyroid ablation or thyroidectomy. Optimal definitive therapy has been debated, and both options can have concerning side effects.[7,8]

Studies have focused on trying to determine predictive factors that increase a patient's likelihood of long-term remission to help families make appropriate treatment decisions.[7–11] Less than 30% of patients achieve remission lasting more than 2 years after ≤24 months of medical therapy.[4,6,9–12] Factors thought to increase a patient's chances of long-term remission include Caucasian ethnicity, prolonged ATD course, older age at diagnosis, and lower free T4 and T3 at onset.[9,10,13] Conversely, characteristics associated with increased risk of relapse after discontinuing medical therapy include ethnic minority, male gender, and higher levels of thyroid antibodies.[9,10] Few studies reviewing remission and relapse rates on medical therapy have included large numbers of ethnic minorities and most have almost exclusively involved female subjects. Our study includes a racially diverse population with a representation of both sexes. We also report on rates of adverse effects in patients treated with methimazole over the last 10 years.

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