Biochemical markers for cardiovascular risk following treatment in endogenous Cushing's syndrome.

Cardiovascular disease has been reported to be more common in patients with endogenous Cushing's syndrome (CS) compared to the normal population. In addition to altered lipid profile, inflammation seems to play an important pathogenic role in atherogenesis, but the role of inflammation in CS-associated cardiovascular disease is still not clear. To further elucidate these issues we measured several markers of inflammation in CS patients at baseline and following operative treatment and potential cure. Twenty-eight CS patients (22 women, 6 men) were included in the study and 21 of these patients (15 women, 6 men) were also followed longitudinally for a mean 33 months (range 5-69 months) after operative treatment. For comparison, blood samples were also collected from 24 healthy controls (21 women, 3 men). We show a distinct cytokine profile in CS patients before and after operative treatment. Thus, while interleukin (IL)-8 and osteoprotegerin (OPG) were significantly increased in CS patients before operation and fell during follow-up, levels of C-reactive protein (CRP) and soluble intracellular adhesion molecule 1 (sICAM) were significantly decreased at baseline, reaching normal levels after operation. While soluble CD40 ligand was within normal limit at baseline, this marker of platelet-mediated inflammation was markedly elevated during follow-up. Our findings suggest a complex interaction between CS and inflammation. In particular, the raised levels of IL-8 and OPG in CS patients, despite glucocorticoid excess, may represent an inflammatory and pro-atherogenic phenotype. However, the clinical relevance of these findings will have to be clarified.