Increased risk of Graves\xb4ophthalmopathy in patients with increasing TRAb after radioiodine treatment and the impact of CTLA4 on TRAb titres

Bushra Shahida,Vijayachitra Modhukur,Peter Åsman,Mikael Lantz,Jan Tennvall,Ola Lindgren,Kleoniki Tsoumani,Pernilla Asp,Anna Sundlöv,Tereza Planck

doi:10.1007/s12020-021-02952-2

Bushra Shahida, Vijayachitra Modhukur + Show 8 more

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https://doi.org/10.1007/s12020-021-02952-2

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Journal: Endocrine	Publication Date: Dec 2, 2021
Citations: 3	License type: open-access

Affiliation: Lund University, Skåne University Hospital

Abstract

IntroductionTreatment of Graves´ disease (GD) with radioiodine increases the risk of developing Graves´ ophthalmopathy (GO), and the link between thyroid and orbital tissue may be the presence of TSH-receptors. Radioiodine increases the titers of TRAb and the aim was to investigate the relationship between GO and TRAb titers after treatment with radioiodine and to define the impact of risk genes.MethodsGD patients without ophthalmopathy or previous treatment with radioiodine were prospectively included at treatment with radioiodine for hyperthyroidism. A follow-up was performed 1 year later for the registration of GO development. The study was performed at a University Hospital Clinic; a referral center of all patients treated with radioiodine in the south of Sweden. The main outcome measures were the development of TRAb, anti-TPO, and anti-TG after 3 months and GO after 12 months and relationship to the genetic background (HLA, CTLA-4, and CYR61).ResultsThree months of radioiodine TRAb titers increased in two thirds of patients (p < 0.0005) but not in the other third. Anti-TPO titers were associated with TRAb (R = 0.362, p < 0.0001) but not anti-TG. At follow-up 1 year later (n = 204) 32 patients developed GO with a proportion of 70% in the group increasing in TRAb titers and 30% in the group with unchanged or lower TRAb titers (p-value < 0.0005). Patients with GO had higher titers of TRAb than patients without GO. CTLA-4 (rs231775 SNP) was significantly (p < 0.005) associated with TRAb titers above the median three months after radioiodine.ConclusionsThe increase in TRAb titers after treatment with radioiodine is associated with GO and a genetic variation in CTLA-4 is associated with higher titers of TRAb.

Highlights

Introduction Treatment ofGravesdisease (GD) with radioiodine increases the risk of developing Gravesophthalmopathy (GO), and the link between thyroid and orbital tissue may be the presence of TSH-receptors
These genes have later been investigated for the presence of gene polymorphisms and we found an association of cysteine-rich 61 (CYR61) with GD and GO, and an increased risk for GO in smokers [13]
At the start of treatment with radioiodine 204 patients were registered and thyroid antibodies; TSH-receptor stimulating antibodies (TRAb), anti-TPO, anti TG were analysed before treatment with radioiodine, and 3 months after radioiodine the antibody analysis was repeated for detection of patients that showed an increase of 1.1 or more

Summary

Introduction

Introduction Treatment ofGravesdisease (GD) with radioiodine increases the risk of developing Gravesophthalmopathy (GO), and the link between thyroid and orbital tissue may be the presence of TSH-receptors. Results Three months of radioiodine TRAb titers increased in two thirds of patients (p < 0.0005) but not in the other third. At follow-up 1 year later (n = 204) 32 patients developed GO with a proportion of 70% in the group increasing in TRAb titers and 30% in the group with unchanged or lower TRAb titers (p-value < 0.0005). A strong risk factor is tobacco smoking which results in higher TRAb at diagnosis of GD and during treatment with thiamazole than non-smokers [3, 4]. Smoking has been shown to increase TRAb titers and the risk of development of GO both at and after diagnosis of GD [5, 6].

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