Endocrine Abstracts

Introduction: Thyroid eye disease (TED) is an immune-mediated disorder of the eye. Intravenous glucocorticoid (GC) is the first-line treatment for active moderate to severe TED patients. However, the rate of response is between 50 and 80%. Reliable and easily accessible markers of responsiveness to GC therapy are still lacking.

Aim of the study: We aimed to explore the possible role of miR-146a and miR-21 as a predictor of responsiveness to GC treatment in TED.

Materials and Methods: We performed a prospective longitudinal study on 30 consecutive adult patients with active moderate to severe TED and eligible for GC therapy. Clinical, ophthalmological and blood samples were collected for each patient before and after treatment. All patients received the standard GC treatment with methylprednisolone iv (cumulative dose of 4.5g). In case of severe diplopia and ocular motility disruption patients underwent also orbital radiotherapy (50%). The response to GC treatment was defined as a decrease of the clinical activity score (CAS) of 2 or more points or disease inactivation (CAS < 3) at 24 weeks.

Results: Twenty-three (77%) patients were considered as responders to GC. Ten patients (33%) experienced at least one side effect related to GC therapy. The baseline circulating miR-146a and miR-21 expression levels were positive correlated (P < 0.0001). Moreover, both miR-146a and miR-21 showed a positive correlation with CAS (respectively P < 0.0001 and P = 0.0076). At univariate analysis thyroid surgery, higher CAS, greater proptosis and higher pre-treatment circulating levels of miR-146a (P = 0.01) and miR-21 (P = 0.03) emerged as predictive factor of responsiveness to GC. A receiver operating characteristic curve analysis (ROC) revealed that both miR-146a (cut-off above 0.45) and miR-21 (cut-off above 0.95) could predict the responsiveness to GC with a PPV of 100%.

Conclusion: This is the first study investigating the role of pre-treatment circulating miR-21 and miR-146a to predict responsiveness to GC therapy in active moderate to severe TED patients. Serum pre-treatment miR-21 and miR-146a emerged as new simple, objective and reliable markers of GC sensitivity. Using a cut-off we could avoid unnecessary GC treatment and direct the therapeutic strategy ab initio towards a second-line therapy especially in the era of precision medicine.