Åse Bjorvatn Sævik, Grethe Ueland, Anna-Karin Åkerman, Paal Methlie, Marcus Quinkler, Anders Palmstrøm Jørgensen, Charlotte Höybye, Aleksandra W J Debowska, Bjørn Gunnar Nedrebø, Anne Lise Dahle, Siri Carlsen, Aneta Tomkowicz, Stina Therese Sollid, Ingrid Nermoen, Kaja Grønning, Per Dahlqvist, Guri Grimnes, Jakob Skov, Trine Finnes, Susanna F Valland, Jeanette Wahlberg, Synnøve Emblem Holte, Olle Kämpe, Sophie Bensing, Eystein Sverre Husebye, Marianne Øksnes
European journal of endocrinology 2023 Oct 17Increased prevalence of cardiovascular disease has been reported in autoimmune Addison's disease (AAD), but pathomechanisms are poorly understood. Cross-sectional study. We compared serum levels of 177 cardiovascular and inflammatory biomarkers in 43 patients with AAD at >18-h 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. Nineteen biomarkers significantly differed between patients with AAD and controls; all but 1 (ST1A1) were higher in AAD. Eight biomarkers were significantly higher in female patients compared with controls (IL6, MCP1, GAL9, SPON2, DR4, RAGE, TNFRSF9, and PGF), but none differed between male patients and controls. Levels of RAGE correlated with the frequency of adrenal crises (r = 0.415, P = .006) and AddiQoL-30 scores (r = -0.347, P = .028) but not after correction for multiple testing. PDL2 and leptin significantly declined 60 min after injection of ACTH in AAD without RAF (-0.15 normalized protein expression [NPX], P = .0001, and -0.25 NPX, P = .0003, respectively). 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. © The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology.
Åse Bjorvatn Sævik, Grethe Ueland, Anna-Karin Åkerman, Paal Methlie, Marcus Quinkler, Anders Palmstrøm Jørgensen, Charlotte Höybye, Aleksandra W J Debowska, Bjørn Gunnar Nedrebø, Anne Lise Dahle, Siri Carlsen, Aneta Tomkowicz, Stina Therese Sollid, Ingrid Nermoen, Kaja Grønning, Per Dahlqvist, Guri Grimnes, Jakob Skov, Trine Finnes, Susanna F Valland, Jeanette Wahlberg, Synnøve Emblem Holte, Olle Kämpe, Sophie Bensing, Eystein Sverre Husebye, Marianne Øksnes. Altered biomarkers for cardiovascular disease and inflammation in autoimmune Addison's disease - a cross-sectional study. European journal of endocrinology. 2023 Oct 17;189(4):438-447
PMID: 37807083
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