High Relapse Rates Follow Children With Graves Disease

Children with Graves disease (GD) possess a high relapse rate following remission, with most happening within 1 year, according to European Thyroid Journal.

Reexamination of thyroid function should occur regularly after drug withdrawal, and medication response and lifestyle of children with GD might affect the prognosis.

This study was conducted because the population of children with GD has attracted widespread attention, but long-term follow-up data are limited, especially in China.

The study authors intended to evaluate the prognosis of GD in children after regular treatments and to pinpoint possible influencing elements.

“Studies have shown that the long-term remission rate of GD children after ATD [thionamide antithyroid drugs] therapy is about 17–33%, which is lower than that of adults, and they are more likely to relapse after ATD withdrawal. Relapse after ATD therapy may lead to prolonged exposure to thyrotoxicosis, resulting in adverse health outcomes,” explained the study authors.

A total of 204 recently diagnosed children with GD in the Children’s Hospital of Nanjing Medical University between 2013 and 2019 were included in this evaluation.

The individuals were divided into groups consisting of the remission group, relapse group, and continuing therapy group depending on therapy outcomes. Relationships between prognosis and possible influencing factors in remission and relapse groups were evaluated.

All 204 children were treated with methimazole at GD presentation. Because of severe complications, 4 (2.0%) cases changed medication to propylthiouracil. Out of all children with GD, 79 (38.7%) had remission, and 40 (50.6%) relapsed following remission. For each additional month prior to when free thyroxine fell into the reference range with treatment, relapse risk grew 1.510 times (OR, 2.510; 95% CI, 1.561-4.034) compared to those in the remission group. Conversely, relapse risk was reduced by .548 times for each additional hour of sleep duration per day (adjusted OR, .452; 95% CI, 0.232-0.879).

“In this study, 204 newly diagnosed GD children were treated with MMI [methimazole] initially. Among them, four cases changed medication to PTU [propylthiouracil] due to significant complications (severe granulocytopenia and systemic allergic reaction),” said the study authors.

Compared with adults, the remission rate among children with GD following ATD treatment was lower, and in the present study, the average length of follow-up for all cases involved was 5 years, ranging from 2 to 8 years), with an overall remission rate of 19.1% (n = 39/204).

little boy with glasses

Additionally in the study, fewer children in the remission group were in puberty and diagnosed at a younger age than those in the relapse group. It was also found that children in the relapse group had significantly more stress and less sleep duration than the remission group, suggesting that environmental factors like sleep and stress might affect GD prognosis after ATD therapy. Stress was also found as a risk factor for prognosis in prepubertal children with GD, while sleep duration was found to be protective, though more research is needed.

In the current study, 104 cases (37.3%) received treatment for over 4 years, and the highest remission rate of 32.1% was seen in cases with 4 years of treatment, with the rate discontinuing increase with a longer treatment duration. So, for children with ATD treatment for more than 4 years without remission, it is vital to consider therapeutic next steps.

Approximately 50.65 (n = 40/79) of patients who were able to stop ATD had a relapse of hyperthyroidism, and 90% (n = 36/40) of them happened within 1 year of ATD withdrawal. So, thyroid function should be regularly examined after ATD withdrawal.

Researchers also emphasized the importance of avoiding iodine during ATD therapy and following withdrawal.

One limitation of this study is that it was a single-center study with the sample size limiting the power of the data. It also did not have some confounding factors like urinary iodine concentration.

“In our study, GD children with 4 years of therapy had the highest remission rate. The relapse rate of children with GD after remission is high, and most of them occur within 1 year after ATD withdrawal. The response of children with GD to ATD, diet, and lifestyle may affect the prognosis. Therefore, it is necessary for clinicians to improve guardians' awareness of GD relapse. Early measures to help children with GD cope with adverse lifestyle might reduce the relapse,” concluded the study authors.

Reference

Cui Y, Chen J, Guo R, et al. Relapse of Graves’ disease in Chinese children: a retrospective cohort study. Eur Thyroid J. Published 0nline April 19, 2023. doi: 10.1530/ETJ-23-0018