The Efficacy and Short- and Long-Term Side Effects of Radioactive Iodine Treatment in Pediatric Graves’ Disease: A Systematic Review

Abstract

<b><i>Background:</i></b> Graves’s disease (GD) is the most common cause of hyperthyroidism. Maximal 30% of pediatric GD patients achieve remission with antithyroid drugs. The majority of patients therefore require definitive treatment. Both thyroidectomy and radioactive iodine (RAI) are often used as definitive treatment for GD. However, data on efficacy and short- and long-term side effects of RAI treatment for pediatric GD are relatively scarce. <b><i>Methods:</i></b> A systematic review of the literature (PubMed and Embase) was performed to identify studies reporting the efficacy or short- and long-term side effects of RAI treatment in pediatric GD. <b><i>Results:</i></b> Twenty-three studies evaluating 1,283 children and adolescents treated with RAI for GD were included. The treatment goal of RAI treatment changed over time, from trying to achieve euthyroidism in the past to aiming at complete thyroid destruction and subsequent hypothyroidism in the last 3 decades. The reported efficacy of a first RAI treatment when aiming at hypothyroidism ranged from 42.8 to 97.5%, depending on the activity administered. The efficacy seems to increase with higher RAI activities. When aiming at hypothyroidism, both short- and long-term side effects of treatment are very rare. Long-term side effects were mainly seen in patients in whom treatment aimed at achieving euthyroidism. <b><i>Conclusion:</i></b> RAI is a safe definitive treatment option for pediatric GD when aiming at complete thyroid destruction. When aiming at hypothyroidism, the efficacy of treatment seems to increase with a higher RAI activity. Prospective studies are needed to determine the optimal RAI dosing regimen in pediatric GD.

2022 European Thyroid Association Guideline for the management of pediatric Graves’ disease

“…Side effects following RAI treatment in pediatric GD patients are extremely rare, although sometimes a mild tenderness over the thyroid may be observed in the first week after treatment. Observational studies in pediatric patients treated with RAI aiming at hypothyroidism reported no malignancies or fertility problems with a maximum follow-up of nearly four decades ( 59 , 63 , 64 , 65 ).…”

“…TSH levels may not normalize for several months after RAI treatment. Patients and parents should be warned about a small risk of thyroid crisis post RAI treatment ( 67 ), although this is extremely rare in children ( 65 ). The first clinical and biochemical evaluation by the pediatric endocrinologist should be scheduled 4–6 weeks after RAI administration but can be brought forward depending on the pre-RAI treatment status.…”

Graves’ disease: moving forwards

“…RAI should be avoided in the very young (<5 years) because of the greater theoretical risk of later malignancy. However, observational studies including a 36-year follow-up study of children aged between 3 and 19 years found RAI to be a safe and effective therapy 32 33. Studies examining the risk of malignancy after RAI are complicated by the fact that hyperthyroidism itself may increase the risk of solid malignancies 34.…”

“…However, observational studies including a 36-year follow-up study of children aged between 3 and 19 years found RAI to be a safe and effective therapy. 32 33 Studies examining the risk of malignancy after RAI are complicated by the fact that hyperthyroidism itself may increase the risk of solid malignancies. 34 A recent review concluded that RAI is similar from a safety perspective when compared with treatment with ATD or surgery.…”

Graves’ Disease in Children: An Update

“…They reported that RI is a safe definitive treatment option for pediatric GD when aiming at complete thyroid destruction. None of the studies included in the review of Lutterman et al 49 reported non-thyroidal malignancies or leukemia later in life, despite long-term follow-up after RI treatment, up to 27 years in some studies.…”