Endocrine Abstracts

Background: Graves’ disease (GD) is the commonest cause of primary hyperthyroidism in iodine-sufficient areas. First-line treatment is a 12-18 month course of anti-thyroid drugs (ATD). However, around 50% of GD patients will relapse, requiring further assessment and definitive treatment with radioactive iodine or thyroidectomy. Identifying risk factors that predict relapse or treatment failure after stopping ATD is important in guiding management. Several risk factors have been reported in the literature from small with moderate-to-high risk for bias trials. We aimed to explore possible risk factors that can assist in identifying patients at high risk of relapse or medical treatment failure, to allow prioritisation for definitive treatment.

Methods: We retrospectively evaluated available data on consecutive patients with first presentation of GD who had positive TSH receptor antibodies (TRAbs), defined as TRAbs>0.4 IU/l, at diagnosis at the Royal Berkshire Hospital and required ATD, between February 2017 and December 2018. Baseline demographics, TRAbs and thyroid function tests (TFTs) levels, and the presence of thyroid eye disease (TED) at diagnosis were recorded. TRAb titres were measured using the RSR Elisa TRAb 2^nd generation assay. FT4 levels were measured using the Roche Cobas Elecsys Gen II assay.

Results: We included 154 individuals. The mean age was 51.6 years, 71.4% were female, and 15% had TED at diagnosis. The median (IQR) TRAb level was 2.7 (1.7, 5.7)IU/l, and the median (IQR) FT4 level was 52.6 (30.3, 81.4)pmol/l. The median follow-up of TFTs was 48 months. Median duration of ATD was 18 months. 102 (66.2%) participants relapsed or had treatment failure (i.e. ATD duration>24 months). Gender did not affect treatment failure (females:65.5% vs males: 68.2%, P0.9). Median TRAb values were similar to those with no relapse (3.6 IU/l vs. 2.4 IU/l, respectively, P0.34). Subsequently, patients were divided into 3 sub-groups according to TRAb values (1st tertile: 0.5-1.9 IU/l, 2nd tertile: 2.0-4.3 IU/l, 3rd tertile: 4.4-31.0 IU/l). Individuals in the 3rd tertile, compared to the 1st, had a higher percentage of TED (30.4% vs. 11.1%, OR 3.5; P0.05), higher FT4 levels (72.4pmol/l vs. 31.6pmol/l; P0.0001) at the time of diagnosis, and significant risk of treatment failure (77.4% vs 54.2%, OR 2.9; P0.02).

Conclusions: Our study showed that patients who present with TED, higher TRAb and FT4 levels at the time of GD diagnosis are more likely to have medical treatment failure or relapse. Early referral for definitive treatment should be considered for such patients.