SAT285 Biomarkers For Cardiovascular Disease And Inflammation Are Altered In Autoimmune Addison's Disease
Authors: Sævik Åse Bjorvatn , Ueland Grethe , Åkerman Anna-Karin , Methlie Paal , Quinkler Marcus , Jørgensen Anders , Höybye Charlotte , Debowska Alexandra W J , Nedrebø Bjørn Gunnar , Dahle Anne-Lise , Carlsen Siri , Tomkowicz Aneta E , Sollid Stina Therese , Nermoen Ingrid , Grønning Kaja , Dahlqvist Per Mikael , Grimnes Guri , Skov Jakob , Finnes Trine Elisabeth , Valland Susanna F , Holte Synnøve E , Wahlberg Jeanette , Kämpe Olle , Bensing Sophie , Husebye Eystein Sverre , Øksnes Marianne 
Published: October 2023

Abstract
Disclosure: Å.B. Sævik: None. G. Ueland: None. A. Åkerman: None. P. Methlie: None. M. Quinkler: None. A. Jørgensen: None. C. Höybye: None. A.W. Debowska: None. B. Nedrebø: None. A. Dahle: None. S. Carlsen: None. A.E. Tomkowicz: None. S.T. Sollid: None. I. Nermoen: None. K. Grønning: None. P.M. Dahlqvist: None. G. Grimnes: None. J. Skov: None. T. Finnes: None. S.F. Valland: None. S.E. Holte: None. J. Wahlberg: None. O. Kämpe: None. S. Bensing: None. E.S. Husebye: None. M. Øksnes: None.
Background: Population-based studies have shown a wider use of cardiovascular medications in AAD and an increased risk of ischemic heart disease, most pronounced in women. These data suggest that a subgroup of patients may be especially vulnerable, emphasizing the need for clinical tools to evaluate cardiovascular risk at an individual level in AAD. Methods: We first mapped 177 cardiovascular and inflammatory biomarkers in patients with AAD compared with healthy controls overall and stratified for sex (false discovery rate, FDR 5%). Second, we explored biomarker associations to the frequency of adrenal crises and quality of life (P&lt;0.050), and any impact of very high ACTH exposure on biomarker profiles by change in biomarker profiles in patients without residual adrenocortical function (RAF) following injection of ACTH (FDR 5%). Results: Nineteen (11%) biomarkers significantly differed between patients with AAD and controls after correction for multiple testing, of which all but one (ST1A1) were higher in AAD. The greatest difference in biomarker value was noted for FGF21 (difference 0.80 NPX, P = 0.004). When stratified for sex, seven of the 19 biomarkers were significantly higher in female patients compared to controls (IL6, MCP1, GAL9, SPON2, DR4, RAGE, TNFRSF9 + PGF), but no significant differences were found between male patients and controls. Levels of RAGE correlated with the frequency of adrenal crisis (r = 0.415, P = 0.006) and AddiQoL-30 scores (r = -0.347, P = 0.028). PD-L2 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). Conclusion: We demonstrate marked differences in cardiovascular and inflammatory biomarker profiles in patients with AAD compared with controls, particularly in women. RAGE might be a marker of disease severity in AAD, associated with the frequency of adrenal crises and reduced quality of life. Very high ACTH levels reduce PD-L2 and leptin in a glucocorticoid-independent manner, although the overall effect on biomarker profiles seems small.
Presentation: Saturday, June 17, 2023