ESPE Abstracts

Introduction: The production of ischemia-modified albumin (IMA) is associated with the production of reactive oxygen species modifying the metal-binding sites of albumin. IMA is considered a non-specific early biomarker in the evaluation of oxidative stress status. Cortisol is known to trigger anti-inflammatory actions through genomic and non-genomic pathways that eventually lead to decreased production of cytokines, chemokines, and inducible nitric oxide synthase, as well as increased anti-inflammatory mediators. However, the effect of ACTH stimulation on IMA levels is unknown. In this study, we aimed to evaluate the effect of ACTH stimulation on IMA levels.

Methods: A total of 99 subjects were enrolled in this study. A standard dose ACTH test was performed to 80 subjects while the remaining 19 subjects were performed low dose ACTH test. To determine cortisol and IMA levels, blood samples were collected at 0, 30, and 60 minutes following the standard dose ACTH test, and at 0 and 30 minutes following the low dose ACTH test.

Results: Peak cortisol levels were lower in subjects given low dose ACTH compared to those given standard dose ACTH with a median value of 22.5 mg/dl (min-max:15.1-27.7) and 31.8 mg/dl (min-max:19.2–41.9), respectively (P:0.0001). No significant changes were detected in IMA levels after low dose ACTH stimulation (P:0.161). However, after standard dose ACTH stimulation, a significant decrease was observed in IMA levels within 30 minutes, and this decrease continued to 60 minutes (P:0.002 and p:0.002). The median value of basal, 30 and 60 minutes IMA levels were 1.22 ABSU (min-max:0.36–1.34), 1.20 ABSU (min-max:0.4–1.30), and 1.20 ABSU (min-max:0.19–1.33), respectively. The difference in IMA levels at 30 minutes and 60 minutes were not significant (P:0.773). A positive correlation was detected between basal and 30 minutes IMA levels (r:0.675, p:0.0001). Furthermore, a weak negative correlation was observed between peak cortisol and IMA levels at 30 minutes (r:-0.233, p:0.02).

Conclusions: To our knowledge this is the first study to show that ACTH stimulation which is known to trigger endogenous cortisol production reduces levels of IMA, an oxidative stress marker, rapidly, in vivo. These results might suggest that the rapid decline in levels of IMA after ACTH stimulation might be mediated by non-genomic pathways of cortisol. On the other hand, the observation of the weak negative correlation between cortisol and IMA levels suggests that ACTH may exert its anti-inflammatory effects directly through the activation of certain melanocortin receptors expressed in peripheral immune cells.