Antibodies against the receptor for insulin-like growth factor 1 (IGF-1RAb), insulin-like growth factor 1 (IGF-1), and insulin-like growth factor binding protein 3 (IGFBP-3) in the serum of patients with Graves' and Basedow's disease with and without orbitopathy.

Introduction: Proven risk factors for thyroid orbitopathy (TO) are thyroid dysfunction, smoking, and high levels of thyrotropin receptor antibodies (TRAb), and the role of insulin-like growth factor 1 (IGF-1), the receptor for IGF-1 (IGF-1R), and antibodies to the receptor for IGF-1 (IGF-1RAb) are also debated. IGF-1R is overexpressed in fibroblasts and orbital lymphocytes in TO patients. It forms a functional complex and mediates signal transduction through thyroid stimulating hormone receptor (TSHR). The study aimed to evaluate the levels of IGF-1RAb, IGF-1, and IGFBP-3 in a group of Graves' and Basedow's disease (GBD) patients with or without TO.

Material And Methods: Sixty-seven patients were included in the study, including 47 GBD and 20 control patients. In the GBD group, 31 patients were diagnosed with active TO and were treated with immunosuppressive therapy according to the standard of European Group on Graves' Orbitopathy (EUGOGO) guidelines. In this group, 10 patients were in the sight-threatening stage of TO severity according to EUGOGO classification. IGF-1 and IGFBP-3 levels were determined with the use of chemiluminescence immunoassay (CLIA) methods. IGF-1RAb was measured by the "in-house" constructed enzyme-linked immunosorbent assay (ELISA) method.

Results: Including our cut-off value (Q75 - 232.48 ng/mL), positive serum IGF-1RAb was found in 25% of patients in the control group (5 out of 20 patients), in 38.3 % (18 out of 47 patients) of patients with GBD, and in 22.5% of GBD patients with active TO (7 out of 31 patients). In GBD patients with active TO, there were no differences in IGF-1RAb when compared to the control group but with a significantly lower level when compared to the GBD patients without active TO. The group of patients with active TO in the sight-threatening stage had significantly lower values of IGF-1RAb compared to the group of patients with GBD without the presence of TO (p = 0.004). There was also a difference in IGF-1RAb concentration between the groups in moderate-to-severe and sight-threatening stages of TO before starting immunosuppressive treatment (p = 0.014). There was no difference in IGF-1 levels between the control group and GBD patients with active TO before starting immunosuppressive treatment and GBD patients without active TO. The was a significant difference in IGF-1 concentration between the group with moderate-to-severe and sight-threatening stages of TO before starting immunosuppressive treatment (p = 0.009). We found significantly lower IGFBP-3 concentrations in GBD patients regardless of the presence of TO compared to the control group (p = 0.016). There was no difference in IGFBP-3 concentrations between patients with moderate-to-severe and sight-threatening stages of TO (p = 0.203).

Conclusion: It seems that high IGF-1RAb levels may have a protective effect against the onset or severe course of TO, and patients with low IGF-1RAb levels are at risk for severe TO. Our results suggest that anti-receptor antibodies to IGF-1 are inhibitory antibodies.