Putative protective role of autoantibodies against the insulin-like growth factor-1 receptor in Graves’ Disease: results of a pilot study

Abstract

Background

The insulin-like growth factor-1 receptor (IGF-1R) is a key element in the pathogenesis of Graves’ Orbitopathy (GO), but the role of IGF-1R autoantibodies (IGF-1RAbs) has not been established.

Methods

We designed a cross-sectional investigation to measure IGF-1RAbs in patients with Graves’ disease (GD), with or without GO, who underwent radioiodine therapy followed by glucocorticoids (GC). Twenty-nine patients were included, 15 of which with GO. Patients were evaluated at baseline and three and 6 months after radioiodine. The primary objective was the prevalence of positive tests for IGF-1RAbs. The secondary objectives were: (1) IGF-1RAbs concentrations and their variations; (2) relationship between IGF-1RAbs and the features of GO; (3) relationship between IGF-1RAbs and anti-thyroid autoantibodies.

Results

IGF-1RAbs above the cut-off value were found only in one patient with GD without GO. IGF-1RAb levels were greater in patients with GD without GO, at baseline (P < 0.0001), and after three (P < 0.0001) and six (P = 0.0001) months. No correlations were observed between IGF-1RAbs and the features of GO, nor between IGF-1RAbs and anti-thyroglobulin or anti-thyroperoxidase autoantibodies. There was an inverse correlation between anti-TSH receptor autoantibodies (TRAbs) and IGF-1RAb levels in GD patients with GO at 6 months (P = 0.03).

Conclusions

IGF-1RAbs appear to be greater in patients with GD without GO compared with those with GO, suggesting a putative protective role of IGF-1RAbs on the development of GO, in line with the beneficial effects of Teprotumumab on GO. The inverse correlation between IGF-1RAbs and TRAbs 6 months after radioiodine may reflect antigen spreading and/or GC treatment.

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Acknowledgements

The study was funded by the University of Pisa (Fondi di Ateneo, to MM).

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Correspondence to M. Marinò.

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All procedure performed in the study involving human participants were in accordance with the ethical standards of the Trust and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Lanzolla, G., Ricci, D., Nicolì, F. et al. Putative protective role of autoantibodies against the insulin-like growth factor-1 receptor in Graves’ Disease: results of a pilot study. J Endocrinol Invest (2020). https://doi.org/10.1007/s40618-020-01341-2

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Keywords

  • Thyroid
  • Graves’ disease
  • Graves’ orbitopathy
  • Graves’ ophthalmopathy
  • Thyroid eye disease
  • Thyroid autoimmunity
  • Autoimmune thyroiditis
  • Insulin-like growth factor-1 receptor