Endocrine Abstracts

Introduction: Cushing`s Syndrome (CS) is associated with endothelial dysfunction and premature atherosclerosis, which occurs due to hypercortisolism itself and associated comorbidities including diabetes and hypertension. Advanced glycation end products (AGE) are heterogeneous compounds produced endogenously from the non-enzymatic glycation of proteins, lipids, and nucleic acids, leading to the activation of various stress-induced transcription factors through the stimulation of oxidative stress, and pro-inflammatory mediators such as cytokines and acute phase proteins, and consequently causes vascular dysfunction. Cardiovascular disease is the main cause of mortality in subjects with CS, and endothelial dysfunction is an early parameter for cardiovascular risk. With the hypothesis that hypercortisolemia in CS may itself lead to endothelial dysfunction by increasing AGE production, we aimed to evaluate microvascular function in CS with carotid intima-media thickness (CIMT) and to investigate the relationship between endothelial dysfunction and AGE.

Methods: Forty patients with active CS and 56 age- and sex-matched subjects without known inflammatory disease were enrolled in this cross-sectional study. Measurement of CIMT was performed by a single blind vascular sonographer using Doppler USG. Serum AGE and carboxymethyl lysine (CML) levels were measured by ELISA.

Results: Age, gender, BMI, the frequency of diabetes mellitus and hypertension were similar in the CS and control groups. While 65% of cases had pituitary Cushing`s disease (n=26), the remaining 14 cases were adrenal CS (35%). CIMT was higher in CS than in the control group (0.615 ± 0.076 mm vs 0.517 ± 0.152 mm; P<0.001), but CML and AGE levels were similar in both groups (p>0.05). After adjustment for diabetes and hypertension, CIMT was still higher in CS but there were no significant differences between the CS and control groups in terms of CML and AGE levels (p>0.05). According to univariate regression analysis, there was no statistically significant association between CIMT and CML, AGE levels.

Discussion: CIMT, an early predictor of subsequent cardiovascular events or mortality, was increased in subjects with CS. Large-scale studies are needed to make definite conclusions about the effect of AGE levels on CIMT.