Clinical characteristics of patients followed with the diagnosis of Graves disease

Introduction: Graves' disease (GD) is the most common cause of hyperthyroidism in childhood and adolescence, characterized by thyrotoxicosis resulting from an autoimmune mechanism. The disease develops as a result of thyroid-stimulating hormone receptor antibodies (TRAb) binding to thyroid-stimulating hormone receptors (TSHR) on thyroid cells, leading to uncontrolled hormone production. Clinically, it manifests with symptoms such as palpitations, tachycardia, weight loss, sweating, and restlessness. Diagnosis is established based on clinical findings as well as evaluation of thyroid function tests and autoantibody levels 1,2. Initial treatment generally involves antithyroid drugs. However, remission rates are low and the risk of relapse is high. Although TRAb levels are considered important markers for disease severity, treatment response, and relapse prediction, this relationship has not been clearly demonstrated in the pediatric population. Moreover, the associations between prognosis and other clinical and laboratory parameters influencing remission and relapse in childhood GD remain insufficiently clarified. Therefore, identifying prognostic markers that may influence disease course in this age group is of clinical significance 3. In this context, this retrospective study aimed to evaluate the clinical, laboratory, and radiological characteristics, medical treatment processes, treatment response times, and drug-related side effects of pediatric patients diagnosed with GD. It also sought to identify potential determinants associated with remission and relapse, thereby contributing to the development of more effective and personalized treatment strategies for pediatric GD. Materials and Methods: This retrospective study included 88 patients aged 1 month to 18 years who were diagnosed with GD and followed for at least 6 months between August 1, 2019, and December 31, 2023, in the Pediatric Endocrinology Clinic of Ankara Bilkent City Hospital. Data were obtained from the hospital's electronic medical records, including medical history, physical examination findings, laboratory and imaging results, treatment process, and drug-related adverse effects. Results: A total of 88 pediatric patients diagnosed with Graves' disease were included in the study. Of these, 79.5% were female and 20.5% were male, with a mean age at diagnosis of 13.6 ± 3.48 years. The most common presenting symptoms were hypermetabolic in nature, including palpitations, tremor, sweating, weight loss, and irritability. On physical examination, exophthalmos was observed in 27.3% of the patients and a palpable goiter in 60.2%. Tachycardia was detected in 48.9%, and hypertension in 28.4% of cases. According to pubertal staging, the majority of the patients (71.6%) were classified as Tanner stage 5. At the time of diagnosis, TRAb positivity was found in 96.6% of patients, anti-thyroid peroxidase antibody (anti-TPO) positivity in 89.8%, and anti-thyroglobulin antibody (anti-Tg) positivity in 60.2%. Thyroid ultrasonography revealed thyroid volume above +2 standard deviation score (SDS) in 76.1% of the patients, parenchymal heterogeneity in 95.5%, hypoechogenicity in 63.6%, and a pseudonodular appearance in 34.1%. All patients were initiated on methimazole therapy. Of these, 89.8% were managed with dose titration and 10.2% with the block-and-replace method. The mean treatment duration was 24.5 ± 14.4 months, while the time to normalization of free thyroxine (fT4) was 2.55 ± 1.99 months. The overall rate of adverse effects associated with methimazole therapy was 17%. Propranolol treatment was initiated in 72.7% of patients, and corticosteroid therapy was used in only one patient. Surgical intervention was performed in 3.4% of the cohort, including two thyroidectomies and one biopsy. The remission rate was found to be 19.3%, and the relapse rate 4.5%. Remission was associated with low levels of TRAb, free triiodothyronine (fT3), and fT4; high thyroid-stimulating hormone (TSH) levels; smaller thyroid volume; absence of exophthalmos and goiter; higher initial drug dosage; longer treatment duration; absence of family history; and older age. The strongest association with relapse was observed in patients with a shorter treatment duration. Although no statistically significant difference was found regarding age, the mean age in the relapse group appeared to be lower. Conclusion: In pediatric cases of Graves' disease, the remission rate achieved with antithyroid drug therapy was found to be low, while the relapse rate was relatively high. Among patients who achieved remission, factors such as low TRAb, fT3, and fT4 levels; elevated TSH levels; smaller thyroid volume; absence of goiter and exophthalmos; prolonged treatment duration; higher initial drug dose; lack of family history; and older age were more prominent. Notably, TRAb level appeared to be a significant predictor of both remission and relapse. Relapse development was statistically significantly associated only with short treatment duration. Although the difference in mean age was not statistically significant, patients who experienced relapse tended to be younger. These findings emphasize the importance of individualized and long-term medical treatment in childhood Graves' disease and suggest that alternative therapeutic approaches should be considered in patients who do not respond to standard treatment or who experience relapse. Keywords: Graves' disease, child, adolescent, TRAb, remission, relapse