Background: The third generation thyrotropin receptor antibodies (TRAb) assay has high sensitivity and specificity in diagnosing Graves disease (GD). Circulating levels of TRAbs predict the disease course of Graves orbitopathy (GO) and remission rates in GD. However, the relationship between TRAb and thyroxine (FT4) and the factors affecting their interaction are unclear.
Method: A prospective cohort study was conducted to evaluate the relationship between TRAbs and free thyroid hormones, as well as to assess the impact of other factors on this relationship. The diagnosis of GD was confirmed in patients with hyperthyroidism by the presence of raised TRAb levels and/or uniform uptake on Technetium scan. The clinical and biochemical information was collated at diagnosis prior to commencement of antithyroid drug therapy. The baseline free thyroid hormones were correlated with TRAbs using linear regression models, which were adjusted for gender, age, coexisting GO and smoking status.
Results: A total of 370 consecutive patients with Graves hyperthyroidism were studied. The mean age (SD) of the patients was 47.6 (15) years and most was females (85%). Serum FT4 levels showed a log-linear relationship with TRAb levels at diagnosis (adjusted R2=0.25). The relationship between TRAb and FT4 was negatively and significantly influenced by age (older patients produced approximately half the serum FT4 concentrations in response to similar TRAb levels than younger ones) and smoking. Conversely, the presence of GO was positively associated with higher serum FT4 levels, independent of TRAb concentrations.
Conclusion: Our data demonstrates a log linear relationship between TRAb and serum FT4 concentrations. Furthermore, aging and smoking are associated with decreased thyrocyte responsiveness to TRAb modulation. Future studies to assess stimulatory and blocking TRAb components may help to provide a mechanistic explanation for this observation. Meanwhile, our data provides useful information for clinicians to help inform treatment decision in managing GD.