Steroid-resistant Graves' orbitopathy: Therapeutic options

Abstract

Graves orbitopathy is the most common extrathyroidal manifestation of autoimmune hyperthyroidism, although it can rarely occur in euthyroid and hypothyroid patients. TSH-receptor antibodies and insulin-like growth factor-1 play a significant role in the pathogenesis of orbitopathy, and orbital fibroblasts are the central site of their action. In addition to the mentioned autoantibodies, T and B lymphocytes, as well as various cytokines, participate in this complex immune process. As the final product of this immune cascade, there is proliferation of fibroblasts, secretion of glycosaminoglycans, differentiation of fibroblasts into myofibroblasts and adipocytes, which is responsible for the appearance of the clinical presentation of orbitopathy. Before starting the therapy, it is necessary to perform a clinical assessment of orbitopathy, which is based on an assessment of the activity and severity of the disease, as well as an assessment of the patient's quality of life. The activity of orbitopathy is assessed based on the clinical activity score. For the severity of the disease the NOSPECS classification, and for the quality of life assessment the specific questionnaire of the European Group for Graves' Orbitopathy can be used. Based on the obtained data, orbitopathy is classified as active/inactive, mild/moderate-to-severe/severe. Treatment of Graves orbitopathy can be specific or supportive. The specific treatment will depend on the degree of clinical activity and severity of the disease, and the degree of impaired quality of life is taken as an additional factor when choosing individual therapy. Intravenous glucocorticoids are the most frequently used first-line therapy for active, moderate-to-severe Graves' orbitopathy, however, a certain number of patients respond poorly to the applied therapy. In such patients, the use of a second line of treatment is indicated. The most commonly used second line of therapy in our country for active, moderate-to-severe glucocorticoid-resistant GO is tocilizumab. We presented a patient with autoimmune thyroid disease who presented with primary hypothyroidism, in whom, despite the use of intravenous glucocorticoids on two occasions, maintained active, moderateto-severe orbitopathy, and therefore the treatment was continued with biological therapy (tocilizumab). A significant beneficial therapeutic effect was achieved with the applied therapy.