[Glucocorticoid-resistant forms of endocrine ophthalmopathy]

Endocrine ophthalmopathy (EO; also called Graves' ophthalmopathy, thyroid eye disease) is a common extrathyroidal manifestation of Graves' disease, characterized by the presence of autoimmune inflammatory process in the orbital soft tissues. The prevalence of EO is approximately 10 cases per 10.000 population, higher in individuals over 50 years old. The pathogenesis of EO is primarily attributed to cross-reactive immune activity between thyroid antigens and orbital soft tissues. Clinically, EO may manifest as involvement of extraocular muscles or orbital fat depending on the affected area. Moderate, severe and very severe forms of EO in terms of disease compensation account for 4.9-10% of cases. For decades, glucocorticoid (GC) therapy has been the treatment of choice; however, up to 20% of EO patients are unresponsive to high-dose GC therapy, and about one-third experience early relapses after discontinuation. Polymorphisms in the glucocorticoid receptor gene NR3C1 have been implicated in GC resistance in patients with autoimmune diseases. However, studies, including clinical observations and genetic analyses, revealed no consistent patterns in the distribution of homozygous and heterozygous genotypes of polymorphic markers A6986G of the CYP3A5 gene, C>T intron 6 of the CYP3A4 gene, and rs6190 of the NR3C1 gene, nor in their influence on GC response. These findings highlight the mechanisms underlying GC resistance in EO.