Altered biomarkers for cardiovascular disease and inflammation in autoimmune Addison's disease - a cross-sectional study

Abstract

Objective: Increased prevalence of cardiovascular disease has been reported in autoimmune Addison's disease (AAD), but pathomechanisms are poorly understood.

Design: Cross-sectional study.

Methods: We compared serum levels of 177 cardiovascular and inflammatory biomarkers in 43 patients with AAD at > 18-hour glucocorticoid withdrawal and 43 matched controls, overall and stratified for sex. Biomarker levels were correlated with the frequency of adrenal crises and quality of life (QoL) by AddiQoL-30. Finally, we investigated changes in biomarker levels following 250 µg tetracosactide injection in patients without residual adrenocortical function (RAF) to explore glucocorticoid-independent effects of high ACTH.

Results: Nineteen biomarkers significantly differed between patients with AAD and controls, all but one (ST1A1) were higher in AAD. Eight biomarkers were significantly higher in female patients compared with controls (IL6, MCP1, GAL9, SPON2, DR4, RAGE, TNFRSF9, PGF), but none differed between male patients and controls. Levels of RAGE correlated with the frequency of adrenal crises (r=0.415, P=0.006) and AddiQoL-30 scores (r=-0.347, P= 0.028), but not after correction for multiple testing. PDL2 and leptin significantly declined 60 minutes after injection of ACTH in AAD without RAF (-0.15 NPX, P=0.0001, and -0.25 NPX, P=0.0003, respectively).

Conclusions: We show that cardiovascular and inflammatory biomarkers are altered in AAD compared with controls, particularly in women. RAGE might be a marker of disease severity in AAD, associated with more adrenal crises and reduced QoL. High ACTH reduced PDL2 and leptin levels in a glucocorticoid-independent manner but the overall effect on biomarker profiles was small.