**8. Adverse events**

Actinic thyroiditis is the result of radioiodine therapy. As radioiodine is accumulated by thyroid cells the emitted betta particles cause cellular necrosis and stored thyroid hormones are released into the circulation causing a transient exacerbation of hyperthyroidism. This effect is greater in radioiodine therapy of a toxic nodular goiter as the levels of stored thyroid hormones are bigger [38]. This transient elevation of thyroid hormones can be asymptomatic or it can lead to atrial fibrillation, heart failure and rarely to thyroid storm with a possible fatal outcome. The latter demands admission to an intensive care unit and administration of ATDs and steroids (intravenously) as well as b-blockers [16].

Hypothyroidism is another side effect of radioiodine therapy and according to the ATA guidelines, it is the main goal of the therapy [12]. This outcome is more common in GD rather than in toxic goiter or in solitary hyperfuctionong nodules [16]. It requires lifelong follow up and LT4 treatment. In cases of failure to accomplish a hypothyroid state post radioiodine treatment, an increase in cardiovascular and cerebrovascular deaths has been noted [12].

Actinic thyroiditis is accompanied by thyroid pain and swelling which is prevalent the first week post therapy. In a few patients this can lead to dyspnea while the majority is asymptomatic. In cases of a large goiter with signs of tracheal compression, corticosteroids before radioiodine therapy should be considered. Sialadenitis, xerostomia or altered taste are adverse effects seen in patients with differentiated thyroid cancer who receive radioiodine therapy, however in patients with GD no permanent damage has been reported.

Ionizing radiation has been associated with increased incidence of leukemia and many solid cancers [39]. An increase in the incidence of thyroid carcinoma in children after Chernobyl accident has been reported [40]. Many studies have evaluated the possible correlation between radioiodine therapy in GD and the risk of malignancy. In a multicenter retrospective cohort study taken place in USA and UK, known as Cooperative Thyrotoxicosis Therapy Follow-up Study Group, 35,593 hyperthyroid patients were included and evaluation of cancer mortality among those patients and especially in those who received radioiodine treatment, was made. The results showed no significant increase in cancer mortality and this was due to the fact that mean doses of radiation among organs except for the thyroid were < 200 mGy. It has to be mentioned that the study cannot provide any information for the children population as themean age of the patients was 46 years [41]. Kitahara et al. [42] extended the previous study and found that radioiodine therapy of GD was correlated with a dose dependent increase in the incidence of all solid tumors and especially of breast cancer, while Greenspan et al., [43] challenged those previous results. Αmeta analysis by Hieu et al., [44] found no increase in cancer risk post radioiodine therapy in benign thyroid disorders except perhaps for the thyroid, kidney and the stomach cancer, which the authors estimate that it should be investigated with further studies. The latter has also been challenged by Salvatori et al., [45] as the main reason for increased incidence of cancer in hyperthyroid patients is not radioiodine therapy but hyperthyroidism

itself. Thyroid hormones through ανβ3, a membrane receptor which is overexpressed in tumor cells, play a crucial role in cancer cell proliferation, angiogenesis and metastasis.
