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Can statins also treat Graves’ ophthalmopathy except lowering lipids?
Can statins also treat Graves’ ophthalmopathy except lowering lipids? Gravesorbitopathy (GO) is the most common extrathyroid manifestation of Graves’ disease (GD). It occurs in 25% ~ 30% of GD patients. It is an organ-specific autoimmune disease. Physical health and mental health cause harm that is difficult to assess, which seriously affects the quality of life of patients.
The currently available treatments for GO include hormone shocks, orbital irradiation and immunomodulators, but none of them can prevent the long-term effects of GO and may cause serious side effects. Therefore, identifying the risk factors that make GD patients develop into GO and making individualized diagnosis and treatment plans can significantly improve the quality of life of these patients.
Currently recognized risk factors related to the occurrence and development of GO and changeable include smoking, radioactive iodine therapy and thyroid dysfunction. However, recent studies have shown that hypercholesterolemia may be a potential risk factor for GO, and statins can reduce the risk of eye disease in patients with newly diagnosed Graves disease.
Many scholars have studied the relationship between the risk of GO and statins in patients with Graves disease. In a recent cross-sectional study , a correlation was found between the occurrence of GO and total cholesterol and LDL-cholesterol. In addition, the study also found that there is a correlation between the clinical activity score and blood lipids of untreated GO patients.
In addition, Reynolds et al.  conducted a retrospective study on 30 patients who were diagnosed with GO and restrictive strabismus at Kellogg Hospital from January 2013 to August 2015. Among them, 12 patients were before the diagnosis of GO Having taken different types of statins for at least 1 year, the results showed that the average number of orbital decompression and strabismus operations performed by these patients was significantly lower than that of other patients.
In GO-related studies, the study by Koch et al.  suggested that statins may turn the main pro-inflammatory T cell response into an anti-inflammatory T cell response by up-regulating TH2 cells and regulatory T cells. Similarly, statins may be able to transfer the pro-inflammatory T cells of a specific disease from the disease site to the blood, thereby achieving relief of clinical inflammation.
Stein et al.  used multivariate Cox regression to determine the risk of developing GO for 8404 American adults newly diagnosed with GD from 2001 to 2009 in the United States. After adjusting for potential confounding factors, it was found that thyroidectomy (HR 0.26) and the use of statins (HR 0.60) were associated with a reduction in the risk of GO. And the study did not find that the use of non-statin cholesterol lowering drugs or COX-2 inhibitors was significantly related to the occurrence of GO.
Similarly, recently, Swedish scholars  explored newly diagnosed GD patients who lived in Sweden from 2005 to 2018 and were ≥18 years old (n = 34894). Using COX regression, the incidence of GO was compared between statin users (n = 5574) and non-statin users (using other lipid-lowering drugs, n = 34409). The study found that the incidence of GO of statin users was significantly lower than that of non-users, and it had a stronger protective effect on men. In addition, the results showed that in addition to statins, other lipid-lowering drugs did not show similar protective effects, and the combination of statins and another lipid-lowering drug did not produce better effects.
At present, the mechanism is still controversial.
(1). Hypercholesterolemia is related to its occurrence and activity level: Recently, in a cross-sectional study of GD patients, it was found that there is a correlation between the occurrence of GO and total cholesterol and LDL-cholesterol, suggesting that cholesterol itself is in GO Play a role in the development of
(2). Statins have anti-inflammatory effects independent of lowering cholesterol: In GO patients, many studies have so far confirmed that statins have anti-inflammatory effects independent of lowering cholesterol levels. Stein’s research shows that statins have beneficial anti-inflammatory effects, but non-statin cholesterol-lowering drugs have not found this effect. This finding led the authors to conclude that the pleiotropic anti-inflammatory effects of statins are responsible for the protective effects of GO patients.
(3). Possible immunomodulatory properties of statins: Rheumatoid arthritis is an autoimmune disease and has some of the same pathogenesis and risk factors as GD. The results of a recent systematic review and a meta-analysis of 15 randomized controlled clinical trials  strongly indicate that statins have beneficial effects in autoimmune diseases, suggesting that they may benefit Graves patients who are also autoimmune diseases , But there is still a lack of relevant clinical research evidence.
(4). Statins may reduce the occurrence of fat: In the study of American scholars, other anti-inflammatory drugs (such as COX-2 inhibitors) did not reduce the harm of GO. This suggests that in addition to reducing inflammation, there may be other mechanisms at play.
Lipogenesis is one of the main reasons for the pathogenic process of GO. In experiments on 3T3-L1 preadipocytes and human orbital fibroblasts , a research team showed that simvastatin has a very strong inhibitory effect on the mRNA expression of early and late adipogenic genes, leading to mature adipocytes amount reduced. Therefore, reducing fat production may also be one of the mechanisms.
Currently, the clinical application of statins is very extensive, and their safety has been verified. Therefore, we may be able to actively use statins for lipid-lowering treatment in patients with Graves disease who have hyperlipidemia.
For patients newly diagnosed with GD, statins are expected to be used as a long-term safe drug to effectively prevent and delay the occurrence and progression of GO. It is expected that there will be more clinical studies in the future to further verify whether statins reduce the risk of eye disease in newly diagnosed Graves disease patients.
(source:internet, reference only)