Statins in Graves Orbitopathy: A New Therapeutic Tool

Purpose: Graves orbitopathy (GO) is the most common extrathyroidal manifestation of Graves disease. Although its pathogenesis is not fully elucidated, GO is commonly considered an autoimmune disease due to loss of self-tolerance against autoantigens shared by thyroid epithelial cells and orbital fibroblasts. High-dose intravenous glucocorticoids (ivGCs) are the most used treatment for moderate-to-severe, active GO, but the addition of other immunomodulating treatments can improve the efficacy of ivGCs. Among the various risk factors that can affect the occurrence of GO, cholesterol may be worthy of interest. Since 2015 the role of cholesterol and cholesterol-lowering medications has been investigated. The purpose of this review is to discuss this topic, thereby offering new therapeutic opportunities for patients with GO. Methods: We searched PubMed for studies published between January 1, 1980 and June 1, 2023, using the search terms “Graves orbitopathy,” “thyroid eye disease,” “Graves ophthalmopathy,” “thyroid ophthalmopathy,” “thyroid-associated ophthalmopathy,” “endocrine ophthalmopathy,” “cholesterol,” “lipids,” “statins,” “low-density lipoprotein,” “atorvastatin,” and “cholesterol-lowering drugs.” Only English-language articles were included. Results: A correlation between low-density lipoprotein cholesterol and the risk of GO development has been reported. Furthermore, low-density lipoprotein cholesterol has been proposed as a risk factor that can affect the course of GO and the response to ivGCs. The protective role of cholesterol-lowering medications in preventing GO has been also investigated. Statin treatment was found to have potential benefits in reducing the risk of GO in patients with Graves disease. Given these findings, measurement of low-density lipoprotein cholesterol and treatment of hypercholesterolemia in patients with moderate-to-severe, active GO may be considered before starting ivGCs administration. Recently, a randomized clinical trial aimed at investigating the effects of statins in GO suggested that the addition of oral atorvastatin to ivGCs improves the overall outcome of moderate-to-severe, active GO in hypercholesterolemic patients given ivGCs. Conclusions: Overall, statins seem to have a preventive and therapeutic role in moderate-to-severe active GO. Their efficacy can be related to cholesterol-lowering activity, pleiotropic actions, and interaction with methylprednisolone.