Pediatric hyperthyroidism and its therapeutic outcomes: A comprehensive comparative review of Graves' Disease, Hashimoto's Thyroiditis, and Hashitoxicosis

Background: Pediatric hyperthyroidism, predominantly caused by Graves’ disease (GD), is a rare endocrine disorder but has serious impacts with systemic consequences that extend beyond thyroid hormone excess. Despite the availability of antithyroid drugs (ATDs), radioactive iodine (RAI), and surgical options, controversy persists regarding optimal therapeutic strategies in children. Additionally, Hashimoto’s thyroiditis (HT), while typically leading to hypothyroidism, can present with transient hyperthyroidism (Hashitoxicosis), which further complicates clinical management. Objective: This review aimed to compare the efficacy and systemic outcomes of ATDs, RAI, and thyroidectomy in pediatric GD; to evaluate the impact of treatment on cardiac, neurological, ocular, and growth outcomes; and to define optimal strategies for managing Hashitoxicosis in children. Methods: We conducted a comprehensive narrative review of studies published between 1998 and 2024. Data from over 60 peer-reviewed studies were analyzed, including randomized controlled trials, cohort studies, and guidelines focusing on pediatric populations with GD, HT, and Hashitoxicosis. Inclusion criteria encompassed studies reporting treatment outcomes, systemic effects, and long-term follow-up in children aged 0–18 years. Outcomes were synthesized across six domains: thyroid function, cardiovascular, neurological, ophthalmologic, linear growth, and autoimmune comorbidities. Results: ATDs, while commonly used as first-line therapy, demonstrated remission rates of 20–30% and relapse rates up to 70%, with modest systemic recovery. RAI and thyroidectomy offered higher remission (~85–99%) and superior improvement in cardiac and neurobehavioral symptoms, linear growth, and eye signs. Thyroid surgery was most definitive but carried procedural risks. In HT-related Hashitoxicosis, the hyperthyroid phase was transient in 90–95% of cases, resolving without ATDs. Levothyroxine therapy in HT stabilized thyroid function in 70–80% of cases and improved subclinical cardiac and growth impairments. Subclinical dysfunction in euthyroid children with HT was detected via advanced imaging and improved with early therapy. Conclusion: Effective treatment of pediatric hyperthyroidism must extend beyond biochemical control to address systemic outcomes. ATDs remain suitable for initial management, but early identification of poor responders should prompt consideration of definitive therapy. RAI and surgery are more effective in restoring multisystem stability, especially in older children. Recognition and conservative management of Hashitoxicosis, alongside timely levothyroxine initiation in HT, are crucial for optimizing outcomes. Tailored, system-informed strategies and long-term surveillance are essential in managing pediatric autoimmune thyroid disorders.