The therapeutic outcome of intravenous steroid therapy for active Graves' orbitopathy is influenced by the time of response but not polymorphisms of the glucocorticoid receptor

Background: Glucocorticoids are the mainstay of immunosuppression for active moderate-severe Graves' orbitopathy (GO). Aim: To analyze the response to therapy and the contribution of glucocorticoid receptor (GR) gene polymorphisms to the therapeutic outcome of intravenous glucocorticoids (IVGC) in active moderate-severe GO. Methods: We have studied 58 patients treated with 7.5 g i.v. methylprednisolone (cumulative dose). Ophthalmological assessment was performed at baseline and at 6-8, 12-16, and 24-30 weeks after the first infusion. Three GR gene polymorphisms, ER22/23EK, N363S, and BCL1, which have been associated to variable sensitivity to steroids, were studied in 43/58 patients. The therapeutic outcomes defined as: i) reduction of the clinical activity score (CAS) ≥2 points or ii) reduction of proptosis ≥2 mmor iii) improvement of diplopia according to the Gorman score were also studied in relation to treatment schedule, age, gender, duration of thyroid or GO, smoking habits, and serum TSH-receptor autoantibodies levels. Results: In total, 70% of patients responded and had GO inactivation (CAS