Relapse of Graves&apos; disease in Chinese children: a retrospective cohort study

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Abstract

Background

Graves' disease (GD) among children has attracted wide attention. However, data on long-term follow-up are scarce, especially in China. This study aimed to investigate the prognosis after regular treatments of GD and to identify possible influencing factors.

Methods

A total of 204 newly diagnosed GD children in the Children's Hospital of Nanjing Medical University between 2013 and 2019 were included in this study. The cases involved were divided into remission group, relapse group, and continuing treatment group according to therapy outcomes. Relationships between prognosis and possible influencing factors in remission and relapse groups were analyzed.

Results

All 204 cases were treated with methimazole at presentation with GD. Due to severe complications, 4 (2.0%) cases changed medication to propylthiouracil. Of all the GD children included, 79 (38.7%) had remission, and 40 (50.6%) relapsed after remission. For each additional month before free thyroxine fell into the reference range with treatment, the risk of relapse increased 1.510 times (adjusted odds ratio (OR)=2.510, 95%CI: 1.561–4.034) compared to those in the remission group. On the contrary, the risk of relapse was reduced by 0.548 times for each additional hour of sleep duration per day (adjusted OR=0.452, 95%CI: 0.232–0.879).

Conclusion

GD children have a high relapse rate after remission, and most of them occur within 1 year. Thyroid function should be reexamined regularly after drug withdrawal. The response to medication and lifestyle of GD children may affect the prognosis.

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Most cited references 23

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

Mireille Castanet, , Juliane Léger … (2008)

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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Positive impact of long-term antithyroid drug treatment on the outcome of children with Graves' disease: national long-term cohort study.

Georges Gelwane, Florentia Kaguelidou, Juliane Léger … (2011)

Drug-based therapy is usually the initial treatment for Graves' disease (GD) hyperthyroidism in children, but there is some debate about treatment duration. Our objective was to assess the effect of long-term carbimazole therapy on GD remission in children and its determinants. This was an observational prospective multicenter follow-up cohort study. Participants included 154 children newly diagnosed with GD between 1997 and 2002. The intention was to treat patients with three consecutive courses of carbimazole, each lasting 2 yr. Definitive treatment was performed in cases of poor compliance with antithyroid drug (ATD) treatment, thyrotoxicosis relapse, or major adverse effects of ATD treatment. The main outcome measure was remission for at least 18 months after the completion of each course of ATD treatment. The median duration of follow-up was 10.4 (9.0-12.1) yr. Overall estimated remission rates (95% confidence interval) 18 months after the withdrawal of ATD treatment increased with time and were 20 (13-26), 37 (29-45), 45 (35-54), and 49 (40-57)% after 4, 6, 8, and 10 yr follow-up, respectively. A multivariate competing risk model revealed an independent positive effect of less severe forms of hyperthyroidism at diagnosis [subhazard ratio of 1 for patients with free T(4) <35 pmol/liter vs. 0.4 (0.20-0.80) for free T(4) ≥ 35 pmol/liter; P = 0.01] and of the presence of other autoimmune conditions [subhazard ratio of 2.23 (1.19-4.18); P = 0.01] on remission rate after medical treatment. About half the patients achieved remission after carbimazole discontinuation, and there seems to be a plateau in the incidence of remission achieved after 8-10 yr ATD therapy.

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Hyperthyroidism in children treated with long term medical therapy: twenty-five percent remission every two years.

Gilaad Kaplan, B M Lippe, Elliot M. Landaw (1987)

We use an antithyroid drug for the treatment of hyperthyroidism due to Graves' disease in children and adolescents for as long as the patients are willing to comply and/or tolerate the drug. In more than 60 patients treated since 1961, the remission rate was 25% in the first 2 yr. This report looks at these same patients again, followed for an additional 5 yr. Survival analysis methods applied to the follow-up data on 63 children confirm our original statistical findings and suggest a continuing remission rate of 25% every 2.1 +/- 0.4 (+/- SE) yr regardless of the duration of previous therapy. The median time to remission was 4.3 +/- 1.5 yr, and 75% of patients are predicted to be in remission in 10.9 +/- 2.3 yr. Of 36 patients who went into remission, defined by their being euthyroid for 1 yr after cessation of therapy, 1 relapsed, and 2 developed spontaneous hypothyroidism; the remainder are euthyroid 1-11.7 yr after therapy was discontinued. Of 14 who switched from medical therapy, 2 of 7 treated surgically and 4 of 7 treated with 131I are hypothyroid. Only 1 patient had a significant adverse reaction to both methimazole and propylthiouracil. While medical therapy may have some direct effect on the autoimmune response in hyperthyroidism, its role in affecting the time to ultimate remission is unknown. These data, however, describe the course of children so treated and allow us to present therapeutic options initially or during treatment based on statistically derived probabilities of outcome.

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Author and article information

Journal

Journal ID (nlm-ta): Eur Thyroid J

Journal ID (iso-abbrev): Eur Thyroid J

Journal ID (publisher-id): ETJ

Title: European Thyroid Journal

Publisher: Bioscientifica Ltd (Bristol )

ISSN (Print): 2235-0640

ISSN (Electronic): 2235-0802

Publication date (Electronic): 21 March 2023

Publication date (Electronic preprint): 21 March 2023

Publication date Collection: 01 June 2023

Volume: 12

Issue: 3

Electronic Location Identifier: e230018

Affiliations

[1 ]Department of Endocrinology , Children's Hospital of Nanjing Medical University, Nanjing, China

[2 ]Department of Cardiology , Children's Hospital of Nanjing Medical University, Nanjing, China

[3 ]Department of Public Health , Children's Hospital of Nanjing Medical University, Nanjing, China

[4 ]School of Public Health , Nanjing Medical University, Nanjing, China

Author notes

Correspondence should be addressed to X Wang: sepnine@ 123456njmu.edu.cn

*(Y Cui, J Chen and Rui Guo contributed equally to this work)

Author information

Xu Wang http://orcid.org/0000-0002-1861-5922

Article

Publisher ID: ETJ-23-0018

DOI: 10.1530/ETJ-23-0018

PMC ID: 10160539

PubMed ID: 36944106

SO-VID: a1bcfc86-cb18-4e1d-9d35-b79184dea90f

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

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Relapse of Graves' disease in Chinese children: a retrospective cohort study

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Most cited references 23

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

Positive impact of long-term antithyroid drug treatment on the outcome of children with Graves' disease: national long-term cohort study.

Hyperthyroidism in children treated with long term medical therapy: twenty-five percent remission every two years.

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