Factors at Onset Predictive of Lasting Remission in Paediatric Patients with Graves' Disease Followed for at Least Three Years

Abstract. In most trials, at least 30-60% of patients with Graves' disease treated with antithyroid drugs relapse within 2 years after therapy withdrawal. At present, there are no prognostic parameters available early in treatment to indicate patients likely to achieve long-term remission. Because thyrotropin receptor autoantibodies (TRAb) are specific for Graves' disease, we evaluated the ability of their levels and of their rate of change to predict long-term prognosis. In our study 216 consecutive patients with newly diagnosed Graves' disease started a therapy with methimazole. Patients were treated until they achieved euthyroidism and TRAb were measured at 6-month intervals throughout a follow up of 120 months. Our study demonstrated that at the onset of hyperthyroidism patients' age, sex, fT4 levels and goiter size had no prognostic value in predicting long-term prognosis (respectively p = 0.79; p = 0.98; p = 0.83; p = 0.89). On the contrary, at the time of diagnosis TRAb titer was a good predictor of the final outcome (p<0.001); a titer equal to (or) more than 46.5 UI/L could identify patients who had never achieved long-term remission with a sensitivity of 52% and a specificity of 78%. Also fall rate of TRAb at 6 months of follow up and after therapy withdrawal were useful to predict the final outcome (p<0.001). At 6 months of follow up the time of therapy withdrawal, a decrease of TRAb lower than 52.3% or even its increase could identify patients who had never achieved permanent remission with a sensitivity of 55% and a specificity of 79.1%. No single parameter among TRAb, satisfactory identified a sub-set of patients who achieved long remission. Accordingly to our data, the best result in predicting long term remission is probably given by the presence of at least one of the two features evaluated at 6 months (TRAb titer and/or percentage of TRAb fall rate), with a sensitivity of 63% and specificity of 88%. TRAb titers evaluated both at the onset of hyperthyroidism that at 6 months of therapy or their rate of fall at 6 months and at ATD withdrawal are predictors of outcome. However, the presence of at least one, between titers of TRAb or their rate of fall at six months, resulted to be the best predictor of remission with the higher sensitivity and specificity.

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“…Our study confirmed previous data [39,40] obtained in adults and in children of the absence of influence of fT4 on the outcome.…”

Section: Discussionsupporting

confidence: 92%

Prognostic Value of Thyrotropin Receptor Antibodies (TRAb) in Graves' Disease: A 120 Months Prospective Study

et al. 2007

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“…However, it is reported that TSAb was correlated with the severity of ophthalmopathy in adult Graves' disease [28,29]. The clinical and biological findings of Graves' disease, including ophthalmopathy, are different with age [4,24,25,27,[30][31][32][33], and so it is possible that this difference might be due to age. However, we examined only the presence of ophthalmopathy, and not its severity, hence further evaluation is needed.…”

Section: Discussionmentioning

confidence: 99%

Assays for Thyroid-stimulating Antibodies and Thyrotropin-binding Inhibitory Immunoglobulins in Children with Graves' Disease

Shibayama

Ohyama²,

Yokota³

et al. 2005

Endocr J

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Abstract. Studies on thyrotropin receptor autoantibodies (TRAb) by measurement of both thyroid-stimulating antibodies (TSAb) and thyrotropin-binding inhibitory immunoglobulins (TBII) in serum from children with Graves' disease are limited in number of studies. The aim of this study was to investigate the levels of serum TSAb and TBII in children with Graves' disease, and to evaluate the clinical significance of these antibodies. We measured the serum TSAb and TBII at diagnosis and during management in 65 children with Graves' disease. Patients were divided into four groups according to their metabolic state: those with untreated active Graves' disease, those receiving treatment with antithyroid drugs, those in remission, and those in relapse. At diagnosis, both TSAb and TBII assays had high sensitivities and high specificities. In follow-up, the levels of both TSAb and TBII paralleled the course of the disease. There was a strong positive correlation between TSAb and TBII. TBII levels were significantly higher in the patients with ophthalmopathy than those without ophthalmopathy in untreated Graves' children. It was concluded that TSAb and TBII measurements are valuable in the diagnosis and management of children with Graves' disease.

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“…Interest in long-term treatment with ATD is also being considered in pediatric patients. Many retrospective studies [19,25,31,32] and one prospective study have shown that the duration of medical treatment may be a predictive marker of relapse in juvenile hyperthyroidism. Another prospective study showed that relapse risk of hyperthyroidism decreased with the duration of the first course of ATD and every additional year of ATD therapy was associated with a decrease in the relapse rate [20].…”

Section: Discussionmentioning

confidence: 99%

Management of thyrotoxicosis in children and adolescents: 35 years’ experience in 304 patients

Azizi

Amouzegar

2018

Journal of Pediatric Endocrinology and Metabolism

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Background: Diffuse toxic goiter accounts for about 15% of all childhood thyroid diseases. There is great controversy over the management of Graves' disease in children and adolescents. This article reports our experience in 304 children and juvenile patients with Graves' disease. Methods: Between 1981 and 2015, 304 patients aged 5-19 years with diffuse toxic goiter were studied, of whom 296 patients were treated with antithyroid drugs (ATD) for 18 months. Patients with persistent or relapsed hyperthyroidism who refused ablative therapy with surgery or radioiodine were managed with continuous methimazole (MMI) treatment. Results: In 304 patients (245 females and 59 males), the mean age was 15.6 ± 2.6 years. After 18 months of ATD therapy, 37 remained in remission and of the 128 who relapsed, two, 29 and 97 patients chose surgery, continuous ATD and radioiodine therapy, respectively. Of the 136 patients who received radioiodine, 66.2% became hypothyroid. Twenty-nine patients received continuous ATD therapy for 5.7 ± 2.4 years. The mean MMI dose was 4.6 ± 12 mg daily, no serious complications occurred and all of them remained euthyroid during the follow-up. Less abnormal thyroid-stimulating hormone (TSH) values were observed in these patients, as compared to patients who were on a maintenance dose of levothyroxine after radioiodine induced hypothyroidism. Conclusions: Original treatment with ATD and subsequent radioiodine therapy remain the mainstay of treatment for juvenile hyperthyroidism. Continuous ATD administration may be considered as another treatment modality for hyperthyroidism.

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Factors at Onset Predictive of Lasting Remission in Paediatric Patients with Graves' Disease Followed for at Least Three Years

Cited by 30 publications

References 11 publications

Prognostic Value of Thyrotropin Receptor Antibodies (TRAb) in Graves' Disease: A 120 Months Prospective Study

Prognostic Value of Thyrotropin Receptor Antibodies (TRAb) in Graves' Disease: A 120 Months Prospective Study

Assays for Thyroid-stimulating Antibodies and Thyrotropin-binding Inhibitory Immunoglobulins in Children with Graves' Disease

Management of thyrotoxicosis in children and adolescents: 35 years’ experience in 304 patients

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