Graves' disease is the most common cause of hyperthyroidism in childhood. As in adults, there are a number of options regarding the treatment of hyperthyroid-ism in children. The three most common treatment options are medical therapy with antithyroid drugs, treatment with RAI, and surgery.
Medical therapy with antithyroid drugs carries a small risk of serious adverse reactions, which include hepatic failure and agranulocytosis. Upon discontinuation of antithyroid drugs, relapse can be expected in the majority of pedi-atric patients (60). With medical therapy, prepubertal children may require many more years of treatment compared with adolescents before antithyroid drugs can be discontinued (61). Surgery for hyperthyroidism may have the highest cure rates of all the treatment modalities. Patients with large glands (>80 g), severe ophthalmopathy, and poor response to other treatments may benefit most from surgery. Surgery may also be preferred for single toxic adenomas to avoid exposure of nonablated thyroid tissue to radiation. However, thyroidectomy carries a small risk of hypoparathyroidism and recurrent laryngeal nerve damage. The success of surgery depends on the experience of the surgeon.
Although RAI is effective, the potential risks related to radiation exposure need to be carefully discussed with the parents or guardians of pediatric patients. Common concerns that may need to be addressed include genetic and oncogenic effects of administering radioactivity, and the potential for radiation exposure to others by young patients in whom proper hygiene may be difficult to maintain.
With external radiation exposure, there is a known risk of thyroid cancer in children that may decrease with increasing age at exposure (62). Studies of radiation exposure related to fallout from nuclear weapon testing in the Marshall Islands and the Chernobyl disaster have also shown higher rates of thyroid cancer in children (63). However, less is known regarding the risk of thyroid cancer following the medical use of RAI in children, and a comprehensive study of thyroid and nonthyroid cancer risks in this setting has not been performed. At prescribed activities of 3.7-7.4 MBq (100-200 pCi) per gram of thyroid tissue, one study did not detect an increased incidence of thyroid cancer in children (64). However, definitive long-term data on the oncogenic effects of therapeutic doses of RAI in children is lacking.
Because of radiation concerns, RAI therapy is often considered as second-line therapy in children. RAI remains efficacious in treating patients who have not responded to other therapies. Second-line indications include failure of antithyr-oid drug therapy, adverse reactions to antithyroid drugs, contraindications or refusal of surgery, and permanent prevention of hyperthyroidism.
Because of the theoretical risk of thyroid cancer after thyroid irradiation in individuals less than 20 years of age, one approach has been to advocate RAI doses sufficient enough to ablate all residual thyroid tissue (65). Such doses also reduce the need for retreatment, thus decreasing the morbidity related to prolonged hyperthyroidism. To achieve ablation in the majority of children with GD, thyroid tissue dose of at least >270 Gy (i.e., 11.1 Mbq/g) may be needed, especially when the gland is large (66). Radiation safety precautions need to be carefully explained to both patients and family members to prevent contamination and unnecessary radiation exposure to others. RAI treatment may not be appropriate in patients who are unable to comply with instructions.
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