Cholesterol and Graves’ Orbitopathy (GO): ‘A new decision-making algorithm based on baseline low density lipoprotein cholesterol (LDLc) and early GO clinical response to parenteral corticosteroids’

Introduction: Parenteral corticosteroids (PC) are effective for the treatment of active moderate to severe (AMS) Graves’orbitopathy(GO). A correlation of GO activity with cholesterol has been described. No evidences are available about cholesterol levels and the clinical efficacy of PC in AMS-GO. Aim: Was to detect the predictive role of cholesterol on medium term clinical outcome of PC therapy in AMS-GO. Methods: We studied 87 patients treated with PC because of AMS-GO. GO evaluation was at baseline, 6 (W6) and 12 weeks (W12) after starting PC. Patients were Improved (I) or Not Improved (NI) by the EUGOGO overall clinical criteria (CI): I or NI W6CI or W12CI and by the Clinical Activity Score (CAS): I or NI W6CAS or W12CAS. Statistic: By univariate and binary logistic regressions analysis setting W12CAS or W12CI categories as outcome variables; independent variables included LDL cholesterol (LDLc), W6CAS or W6CI categories. For the W12 outcome by CAS (W12CAS) regression model, the best cut-off was calculated by ROC curve analysis and by Youden’s test. Results: We retrospectively studied 22 males and 65 females, median age 45 years, who received a median PC cumulative dose of 52.3 g/kg body weight. Responders at W6 (early responders) showed a 13 times greater chance to be classified as improved at week 12 when compared to early not responders (OR 13.7 and 13.1, P < 0.001). NI-W12CAS patients had a higher baseline LDLc cholesterol than I-W12CAS patients (mean rank 40.95 vs 30.49; P = 0.045 respectively). The regression model built for W12CAS outcome was statistically significant, χ2(2) = 15.985, P < 0.001 and both W6CAS and LDLc resulted statistically significant predictor variables. By binary logistic regression results, we built a predictive model: , where x1 = LDLc (mg/dl); x2 = W6CAS outcome (x2 = 1 for IW6CAS; x2 = 0 for NIW6CAS). ROC analysis and Youden’s test identified a predicted probability of improving at W12CAS = 0.664 as best cut-off. A W6CAS and LDLc based decision--making algorithm was finally elaborated: LDLc > 190 mg/dl suggests to treat hypercholesterolemia before to start PC therapy being too low the chances to reach a W12CAS improvement. Conclusions: Early clinical response to corticosteroids is determinant of the 12 weeks AMS-GO clinical outcome when evaluated both by CAS and CI. LDLc improves the predictivity of W12CAS final outcome, LDLc baseline levels > 190 mg/dl reduce the chances of improving at 12W by CAS independently of early W6CAS response