Department of Clinical Science, University of Bergen, Bergen 5021, Norway.
K.G. Jebsen Center for Autoimmune Disorders, University of Bergen, Bergen 5021, Norway.
Eur J Endocrinol. 2023 Oct 17;189(4):438-447. doi: 10.1093/ejendo/lvad136.
Increased 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.
自身免疫性艾迪生病（AAD）患者心血管疾病的患病率增加，但发病机制尚不清楚。
横断面研究。
我们比较了 43 例 AAD 患者（>18 小时糖皮质激素停药）和 43 例匹配对照者的血清中 177 种心血管和炎症生物标志物的水平，总体上和按性别分层比较。通过 AddiQoL-30 将生物标志物水平与肾上腺危象的频率和生活质量（QoL）相关联。最后，我们在没有残留肾上腺皮质功能（RAF）的患者中研究了 250μg 促皮质素注射后生物标志物水平的变化，以探索高 ACTH 的糖皮质激素非依赖性作用。
AAD 患者和对照组之间有 19 种生物标志物水平显著不同；除 ST1A1 外，AAD 患者的所有标志物均升高。与对照组相比，女性患者的 8 种生物标志物水平显著升高（IL6、MCP1、GAL9、SPON2、DR4、RAGE、TNFRSF9 和 PGF），但男性患者与对照组之间无差异。RAGE 水平与肾上腺危象的频率相关（r = 0.415，P =.006）和 AddiQoL-30 评分（r = -0.347，P =.028），但在多重检验校正后无差异。在没有 RAF 的 AAD 中，PDL2 和瘦素在 ACTH 注射后 60 分钟时显著下降（-0.15 个标准化蛋白表达 [NPX]，P =.0001，和-0.25 NPX，P =.0003）。
与对照组相比，我们发现 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 疾病严重程度的标志物，与更多的肾上腺危象和降低的 QoL 相关。高 ACTH 以糖皮质激素非依赖性方式降低了 PDL2 和瘦素水平，但对生物标志物谱的总体影响较小。
