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.

中文翻译：

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自身免疫性艾狄生氏病心血管疾病和炎症生物标志物的改变——一项横断面研究。

目的 据报道，自身免疫性阿狄森氏病（AAD）心血管疾病的患病率增加，但其病理机制仍知之甚少。设计横断面研究。方法 我们比较了 43 名 AAD 患者在糖皮质激素停药 > 18 小时后的 177 种心血管和炎症生物标志物的血清水平，以及 43 名匹配的对照者的血清水平，总体并按性别分层。根据 AddiQoL-30，生物标志物水平与肾上腺危象的频率和生活质量 (QoL) 相关。最后，我们研究了无残余肾上腺皮质功能 (RAF) 的患者注射 250 µg 四糖肽后生物标志物水平的变化，以探索高 ACTH 的糖皮质激素独立效应。结果 AAD 患者和对照组之间有 19 项生物标志物存在显着差异；除 1 (ST1A1) 外，其余所有 AAD 均较高。与对照组相比，女性患者的 8 种生物标志物显着较高（IL6、MCP1、GAL9、SPON2、DR4、RAGE、TNFRSF9 和 PGF），但男性患者和对照组之间没有差异。RAGE 水平与肾上腺危象频率 (r = 0.415，P = .006) 和 AddiQoL-30 评分 (r = -0.347，P = .028) 相关，但在多次测试校正后不相关。在没有 RAF 的 AAD 中注射 ACTH 60 分钟后，PDL2 和瘦素显着下降（分别为 -0.15 标准化蛋白表达 [NPX]，P = .0001 和 -0.25 NPX，P = .0003）。结论 我们发现，与对照组相比，AAD 患者的心血管和炎症生物标志物发生了改变，尤其是女性。RAGE 可能是 AAD 疾病严重程度的一个标志，与更多的肾上腺危象和生活质量下降相关。高 ACTH 以不依赖糖皮质激素的方式降低 PDL2 和瘦素水平，但对生物标志物谱的总体影响很小。