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Altered biomarkers for cardiovascular disease and inflammation in autoimmune Addison's disease - a cross-sectional
Åse Bjorvatn Sævik1,2, Grethe Ueland1,2,3, Anna-Karin Åkerman4,5
1Department of Clinical Science, University of Bergen, Bergen 5021, Norway.
Insights
Cardiovascular and inflammatory biomarkers are altered in autoimmune Addison's disease (AAD), especially in women. RAGE may indicate disease severity, correlating with adrenal crises and reduced quality of life.
Area of Science:
- Endocrinology
- Immunology
- Cardiovascular Medicine
Background:
- Autoimmune Addison's disease (AAD) is linked to increased cardiovascular disease prevalence.
- The underlying pathomechanisms connecting AAD and cardiovascular issues remain unclear.
Purpose of the Study:
- To compare cardiovascular and inflammatory biomarker profiles in AAD patients versus controls.
- To investigate the association of biomarkers with disease severity (adrenal crises, quality of life).
- To explore the effects of high ACTH on biomarker levels, independent of glucocorticoids.
Main Methods:
- A cross-sectional study comparing 43 AAD patients (post-glucocorticoid withdrawal) with 43 matched controls.
- Serum levels of 177 biomarkers were analyzed, stratified by sex.
- Biomarker correlations with adrenal crisis frequency and Quality of Life (QoL) were assessed.
- ACTH (tetracosactide) injection effects were studied in AAD patients without residual adrenocortical function.
Main Results:
- Nineteen biomarkers differed significantly between AAD patients and controls; most were elevated in AAD.
- Eight biomarkers were significantly higher in female AAD patients compared to controls.
- Receptor for Advanced Glycation Endproducts (RAGE) levels correlated with adrenal crisis frequency and reduced QoL.
- ACTH injection decreased PDL2 and leptin levels in AAD patients lacking residual adrenocortical function.
Conclusions:
- Cardiovascular and inflammatory biomarkers are dysregulated in AAD, particularly in women.
- RAGE may serve as a biomarker for AAD severity, linked to increased adrenal crises and diminished QoL.
- High ACTH influences biomarker levels (PDL2, leptin) independently of glucocorticoids, though the overall impact is modest.
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-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.
Results:
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).
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.
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