Endocrine Abstracts

Background: Cushing’s syndrome is a well-known risk factor for endothelial dysfunction, cardiovascular morbidity and mortality.

Objectives: We aimed to prospectively investigate changes in metabolic and cardiovascular parameters and their correlations with markers of endothelial function in patients with endogenous Cushing syndrome following remission.

Methods: Adult patients newly diagnosed with endogenous Cushing’s Syndrome (Cushing’s disease(CD) or adrenal Cushing’s) and a control group matched in terms of age, gender, BMI, lipid, and glucose parameters were enrolled. Metabolic (BMI, body composition analyses, glucose, lipid values) and cardiovascular evaluation studies (echocardiography, 24-hour ambulatory blood pressure monitoring, carotid intima-media thickness(CIMT), flow-mediated dilation(FMD)) were performed and markers associated with endothelial function (asymmetric dimethylarginine(ADMA), interleukin-1β(IL-1β), nitric oxide(NO), endothelin-1(ET-1)) were measured before and one year following remission. Spearman’s correlation analysis was used to investigate the association between variables.

Results: Twenty-five patients (CD(n=9); adrenal Cushing’s(n=16)), mean age 40.60±14.04 years, completed the study. Ten patients had type 2 diabetes mellitus and 13 had hypertension that was well-controlled before surgery. Compared to controls(n=22) total, daytime and nighttime mean arterial pressures(MAP) and CIMT were higher and FMD lower in patients. Baseline serum IL-1β, NO, ADMA and ET-1 were similar between the groups. Patients’ serum ET-1 and IL-1β were negatively correlated with CIMT at baseline (r=-0.465, P = 0.025 and r=-0.567, P = 0.005, respectively). All patients were in complete remission one year following surgery. After remission, BMI, total cholesterol, LDL, total, daytime, nighttime MAP and CIMT significantly decreased. Serum ET-1 levels significantly increased (P = 0.011), while ADMA, IL-1β and NO remained similar one year after remission. Subgroup analysis comparing patients with and without hypertension revealed increase in ADMA and ET-1 levels in the hypertensive group following remission while there was no change in the normotensive group.

Conclusions: There is a significant improvement in metabolic parameters, MAPs, CIMT in patients with Cushing’s syndrome at the first year following remission. The unexpected increase in ET-1 needs to be further investigated.