Age may influence the impact of TRAbs on thyroid function and relapse-risk in patients with Graves' disease.

Context

Thyrotropin receptor antibodies (TRAbs) play a crucial role in the pathogenesis of Graves' disease (GD). However, factors that influence the association of TRAbs with thyroid hormones and relapse risk in GD remain unclear.

Objective

We investigated: (i) the associations of TRAbs at diagnosis with thyroid hormones and relapse risk; (ii) potential factors that can influence these associations in GD.

Design and Setting

A prospective study in GD patients from a single endocrine centre in the north-east of England, seen between January 2008 and March 2018.

Patients and Main outcome measures

Consecutive GD patients (n=384) who had measurements of TRAbs, free thyroxine and free triiodothyronine at diagnosis. The association of TRAbs with thyroid hormones and relapse risk was assessed through linear regression and Cox proportional hazard models, adjusted for potential confounders.

Results

TRAbs were non-linearly associated with thyroid hormones, following a curve with an initial positive slope and a subsequent flattening (p-values <0.0001). Higher TRAbs were also associated with greater relapse risk (Hazard ratio [HR], 1.05; 95% confidence interval [95%CI], 1.02-1.08, per 1 U/L increase in TRAb; p-value 0.001). These associations were modified by age, but not by sex, race, smoking or thyroid peroxidase antibody levels. In younger participants, increasing TRAbs were associated with higher thyroid hormones, and greater relapse risk (HR, 1.13; 95%CI, 1.04-1.23, per 1 U/L increase in TRAb; p-value 0.005). In older participants, increasing TRAbs were not associated with meaningful increases in thyroid hormones or relapse risk (HR, 0.99; 95%CI, 0.93-1.05, per 1 U/L increase in TRAb, p-value 0.7).

Conclusions

In GD, age can influence the impact of TRAbs on thyroid function and relapse risk. TRAbs at diagnosis have better predictive value in younger patients with GD.