Endocrine Abstracts

Objectives: A sporadic association between thyroid and non-organ-specific autoimmunity has been reported, which could be relevant for Graves’ orbitopathy (GO), an autoimmune disease affecting orbital connective tissue. We investigated whether there is an association between GO and anti-nuclear antibodies (ANAs).

Methods: We performed a cross-sectional investigation in 265 consecutive patients with Graves’ disease (GD) who came to our observation over 36 consecutive months to undergo radioiodine treatment. One-hundred and fifty-eight of them had GO, whereas 107 had no GO. The primary outcome was the prevalence of ANAs in patients with GO vs those without GO. The secondary outcomes were: 1) relationship between ANAs and GO features; 2) prevalence of ANAs in GD compared with nonautoimmune hyperthyroidism, namely 78 consecutive patients with toxic nodular goiter (TNG) who came to our observation over the same period to undergo radioiodine treatment.

Results: ANAs were detected in 212 (80%) GD patients, in all cases at low titres, namely 1:80 (98 patients, 46.2%) and 1:160 (114 patients, 53.7%). The prevalence of detectable ANAs did not differ between patients with GO (79.7%) and those without GO (80.3%; OR 0.96; 95% CI from 0.51 to 1.77; P=0.9). However, the prevalence of patients with higher ANA titres (1:160) was greater in GO patients (51.5 vs 38.3%), although the difference was only nearly statistically significance (OR 0.58; 95% CI from 0.33 to 1.02; P=0.059). Within GO patients, proptosis was significantly lower in ANA-positive patients (mean difference -1.42; 95% CI from -2.51 to -0.32; P=0.011). Although CAS and eyelid aperture were lower in ANA-positive patients, differences were only nearly statistically significant (CAS: Mann-Whitney U -1.557; P=0.077; eyelid aperture: mean difference -0.98; 95% CI from -2.01 to 0.05; P=0.062). The distribution of Gorman’s score for diplopia did not differ between ANA-positive and ANA-negative patients. The proportion of patients with detectable ANAs in TNG patients was significantly greater than that in GD patients (91 vs 80%; OR 0.39; 95% CI from 0.17 to 0.9; P=0.028).

Conclusions: Within GD, ANAs are not more frequent in GO. However, they seem to exert a protective role on GO severity and on thyroid autoimmunity in general. A possible explanation is that ANA-related autoimmunity has an immunological phenotype different from the one of thyroid autoimmunity, in which ANA-positive patients may have a switch of the T-cell population that could result in a milder clinical GO picture. Further studies are needed to investigate the mechanisms underlying our observations.