Abstract
BackgroundHigh dose intravenous glucocorticoid (ivGC) therapy is the first line treatment in moderate to severe Graves’ ophthalmopathy (GO) and is associated with a clinical response rate ranging from 50% to 80%. Recently, a positive correlation between total cholesterol and low-density lipoproteins cholesterol (LDLc) with GO presentation and activity has been described.ObjectiveWe aimed at evaluating whether, in patients with moderate to severe active GO treated with ivGC therapy, cholesterol, and LDLc could represent valuable predictive factors of medium-term GO outcome.MethodsThis single center retrospective study was conducted in a consecutive series of 87 patients undergone ivGC therapy because affected by moderate to severe active GO. Clinical outcome of GO was evaluated at week 6 (W6) and 12 (W12) in respect to baseline conditions (week 0) by the seven points CAS according to EUGOGO recommendations. Univariate analysis and binary logistic regression were performed for the outcome variable W12CAS.ResultsIn patients with active GO, an early positive clinical response to ivGC therapy (as evaluated by CAS at 6W) was a strong determinant (OR=13) of the clinical outcome at week 12. Moreover, high levels of LDLc at baseline were positively associated with a reduction in the likelihood of being classified as improved at 12W. Patients with LDLc >193.6 mg/dl were very likely to respond negatively to ivGC therapy independently from the response at 6W. Based on these results, we propose a predictive decision-making model to be tested in future prospective studies.DiscussionWe found that, in patients with active GO, both an early clinical response to ivGC therapy and baseline LDLc levels are significant determinants of GO outcome (W12CAS). These data support the need of a cholesterol-lowering treatment before addressing these patients to ivGC therapy.
Highlights
Graves’ disease (GD) is an autoimmune disorder associated with the production of activating autoantibodies to the thyroidstimulating hormone receptor (TSH-R) in the thyroid gland, leading to hyperthyroidism
The only two variables positively associated with Graves’ ophthalmopathy (GO) improvement at 12W (IW12CAS) were serum levels of low-density lipoproteins cholesterol (LDLc) (r= -0.25, p=0.045) and early improvement at week 6 (W6) (IW6CAS) (p
We found that in patients with active GO addressed to pulse therapy with corticosteroids, baseline serum levels of LDLc and early clinical response at week 6 (W6CAS) were the strongest determinants of the clinical outcome at week 12 according to CAS evaluation (W12CAS)
Summary
Graves’ disease (GD) is an autoimmune disorder associated with the production of activating autoantibodies to the thyroidstimulating hormone receptor (TSH-R) in the thyroid gland, leading to hyperthyroidism. A major extra-thyroidal complication of GD is Graves’ ophthalmopathy (GO), an autoimmune and inflammatory condition characterized by orbital disfigurement, double vision, and decreased visual performance up to blindness (sight-threatening GO) All these factors are associated with proven decrease of quality of life and negative social impact [1, 2]. A significant correlation of GO presentation and activity with total cholesterol and LDLc has been described [9] revealing a role of cholesterol in the processes involved in GO pathogenesis Those data suggest the possibility that cholesterol might increase the risk of GO and its activity, corroborating previous data showing that chronically elevated cholesterol increases systemic inflammation and modulates innate and adaptive immunity [10]. A positive correlation between total cholesterol and low-density lipoproteins cholesterol (LDLc) with GO presentation and activity has been described
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