Table 1.

This Risk factors for Graves’ orbitopathy.

Gender	- In women GO is more frequent [26,27]. - In men GO is more severe [26].
Race	- In Caucasians GO is more frequent than in Asians [29].
Genetics	- Mostly similar to Graves’ disease [23]. - Some studies evaluated immunomodulatory genes including: human leukocyte antigen-DR3 (HLA-DR3), interleukin-1 (IL-1), IL-23 receptor (IL-23R), CD40, cytotoxic T lymphocyte antigen (CTLA-4), T-cell receptor β-chain (TCR-β), protein tyrosine phosphatase non-receptor type 22 (PTPN22), tumor necrosis factor-β (TNF-β) and numerous immunoglobulin heavy chain-associated genes [25]. - Due to the involvement of TSH-R into the patoghenesis of GO the TSH-R gene polymorphisms were studied [24]. However, none of the polymorphisms have proved adequately predictive to support genetic testing in determining prevention methods and further diagnostic and therapeutic process. - Moreover, the increased orbital adipogenesis in GO contributed to genetic testing of the adipogenesis-related gene peroxisome proliferator–associated receptor-γ (PPAR-γ) [24].
GD duration	- The longer duration of GD-related hyperthyroidism the higher risk of GO [30].
Age	- Older age of GD onset is associated with higher risk of GO development [30]. - Older age of GO onset is associated with more severe course of the disease [26].
Exogenous factors	Active or passive smoking: Higher risk of de novo development of GO [14,24] More severe course of GO [33,34,35] The outcomes of the GCs treatment are delayed and limited [33,34,35] Higher TRAb titers and longer persistence during/after the treatment of GO [31] Higher de novo occurrence or exacerbation of GO after radioiodine in smokers [36,37] Radioactive iodine therapy [5,31].
Biochemical factors	- Thyroid dysfunction—both hyper and hypothyroidism—is associated with a greater risk of development, progression, and severe course of GO compared to euthyroid patients [38]. - High TSHR antibody titers increase the risk of GO development, positively correlate with the activity and severity of the disease and are a predictor of poor response to the to immunosuppressive treatment and the risk of relapse after treatment [31].

GO: Graves’ orbitopathy.