Pediatric differentiated thyroid carcinoma: Diagnosis, outcome and late effects of treatment

Pediatric differentiated thyroid carcinoma (DTC) is rare, but its incidence is increasing. Compared to adults, children often present at a more advanced tumor stage and show higher recurrence rates. Nevertheless, the prognosis of pediatric DTC is favorable. However, long-term follow-up data, especially regarding treatment-related complications, are scarce. In this thesis we aimed to evaluate the outcome, surgical complications, and late effects of radioiodine (131-I) treatment and TSH suppressive therapy, as well as quality of life, in survivors of pediatric DTC treated in the Netherlands. In this group, we also aimed to evaluate the presence of somatic genetic alterations, and their relationship with clinical presentation and long-term outcome, as well as miRNA expression. The nationwide study described in this thesis has confirmed the favorable prognosis of patients with pediatric DTC in terms of survival after a median follow-up of 13.5 (range 0.3-44.7) years. However, we have also described frequent treatment-related complications. Life-long postoperative complications occurred in almost one-third of the survivors. Salivary gland dysfunction was present in 47.6% of survivors treated with 131-I. Diastolic dysfunction was present in 21.2% of the survivors. Decreased diastolic function was not associated with TSH levels and cumulative administered 131-I dose. Atrial fibrillation was not observed. We found overall normal health-related quality of live, fatigue, anxiety, and depression in the survivors compared to matched controls. The somatic gene alterations studied were associated neither with the initial tumor staging nor the clinical outcome. A significant association was found between increased miRNA expression and the diagnosis of PTC