Increased Risk of Graves´ophthalmopathy in Patients With Increasing TRAb After Radioiodine Treatment and the Impact of CTLA4 on TRAb Titres

Abstract

Introduction. Treatment of Graves´ disease (GD) with radioiodine increases the risk of developing Graves´ ophthalmopathy (GO) but the link between thyroid and orbital tissue remains undefined.The aim was to investigate the relationship between GO and TRAb after treatment with radioiodine and to define the impact of risk genes.Methods. GD patients without ophthalmopathy or previous treatment with radioiodine were prospectively included at treatment with radioiodine for hyperthyroidism. A follow-up was performed one year later for registration of GO development. The study was performed at a University Hospital Clinic; referral center of all patients treated with radioiodine in the south of Sweden. The main outcome measures were development of TRAb, anti-TPO, anti-TG after three months and GO after 12 months and relationship to the genetic background (HLA, CTLA-4, CYR61).Results. Three months of radioiodine TRAb increased in two thirds of patients (p<0.0005) but not in the other third. Anti-TPO was associated with TRAb (R=0.362, p <0.0001) but not anti-TG. At follow-up one year later (n=204) 32 patients developed GO with a proportion of 70% in the group increasing in TRAb and 30 % in the group with unchanged or lower TRAb (p-value <0.0005). Patients with GO had higher levels of TRAb than patients without GO. CTLA-4 (rs231775 SNP) was significantly (p<0.005) associated with TRAb levels above the median three months after radioiodine.Conclusions. The increase in TRAb after treatment with radioiodine is associated with GO and a genetic variation in CTLA-4 is associated with higher levels of TRAb.