Endocrine Abstracts

The insulin-like growth factor-1 receptor (IGF-1R) is involved in the pathogenesis of Graves’ orbitopathy (GO) and a possible protective role of autoantibodies against IGF-1R (IGF-1R-Abs) has been suggested. We conducted a cross-sectional study to investigate IGF-1R-Abs serum levels in 147 consecutive patients with Graves’ disease (GD), with (n = 92) or without (n = 55) GO (primary outcome). Secondary outcomes were: 1) relationship between IGF-1R-Abs and GO features; 2) effect of IGF-1R-Abs on cell proliferation in primary cultures of orbital fibroblasts. IGF-1R-Abs were measured by ELISA. Serum IGF-1R-Abs levels were higher (29.3 ng/ml, IQR 17.4-36.6) in patients without GO than in those with GO (19.8 ng/ml, IQR 11.2-29.8; Mann Whitney U 1,819, P = 0.00509). The prevalence of IGF-1R-Abs levels above a previously established cut-off value of 55 ng/ml did not differ statistically between the two groups, in spite of a trend to a greater prevalence in patients without GO (9 vs 3.2%). Within GO patients, IGF-1R-Abs did not correlate with GO features, namely proptosis, clinical activity score, eyelid width and visual acuity, whereas there was a correlation with diplopia. Thus, IGF-1R-Abs were lower in patients with the most severe degrees of diplopia (Omega square=0.0123, P = 0.035). Incubation of a thyroid cell line (FRTL-5 cells) with IgGs purified from a pool of sera with IGF-1R-Abs >55 ng/ml increased cell proliferation in a dose-dependent manner (Omega square=0.965; P < 0.0001), presumably reflecting TSH-receptor stimulating antibodies, whereas proliferation was reduced in a dose-dependent manner in orbital fibroblasts from GO patients (Omega square=0.747; P < 0.0001), suggesting a role of IGF-1R-Abs. Overall, our findings suggest that IGF-1R-Abs are present only in a minority of patients with GD and seem to play a protective role on GO development and features.