OBJECTIVE This study aims to identify susceptibility markers for adrenal crises (AC) in educated patients with chronic adrenal insufficiency (AI). DESIGN A case-control study involving 66 patients with AI analyzing the impact of glucocorticoid and mineralocorticoid exposure, adrenomedullary function, inflammatory parameters, and educational status on AC frequency. Patients were categorized into low (n = 32) and high (n = 34) AC frequency groups based on AC occurrence (below or 2 times above the average of the reported AC frequency of 8.3 AC/100 patient-years in a previous prospective study). METHODS Parameters, including cortisol plasma profile and urinary steroid excretion after administration of the morning glucocorticoid dose, 24-h urinary steroid profiling, salivary cortisol profiling, and hair cortisol, estimated cortisol exposure. Polymorphisms (single nucleotide polymorphism [SNP]) of the glucocorticoid receptor (NR3C1) and mineralocorticoid receptor (NR3C2) associated with individual steroid sensitivity were assessed together with SNPs for 11β-hydroxysteroid dehydrogenase 1 (HSD11B1) and 11β-hydroxysteroid dehydrogenase 2 (HSD11B2). Mineralocorticoid replacement was evaluated by serum and urinary electrolytes and osmolality, plasma-renin concentration, and ambulatory blood pressure levels. We additionally measured plasma and urinary catecholamines, serum levels of IL6 and hsCRP, and SNPs of IL6 and TNF-alpha. Patient knowledge of AC prevention was assessed by questionnaires. RESULTS Frequent AC patients had higher daily glucocorticoid doses and hair cortisol levels, with no significant differences in other parameters investigated. AC frequency is inversely correlated with the frequency of self-reported adjustments of the glucocorticoid replacement. CONCLUSION Higher glucocorticoid dosages in high-risk patients, despite unaffected cortisol metabolism, may be linked to decreased cortisol sensitivity or impaired glucocorticoid absorption. Proactive dose adjustments show a protective effect against AC, regardless of biological vulnerability.

中文翻译：

---

慢性肾上腺皮质功能减退症中肾上腺危象的诱发因素：病例对照研究。

目的 本研究旨在确定受过教育的慢性肾上腺功能不全 (AI) 患者的肾上腺危象 (AC) 易感性标志物。设计一项病例对照研究，涉及 66 名 AI 患者，分析糖皮质激素和盐皮质激素暴露、肾上腺髓质功能、炎症参数和教育状况对 AC 频率的影响。根据 AC 发生率，将患者分为低 AC 频率组 (n = 32) 和高 AC 频率组 (n = 34)（低于或高于先前前瞻性研究中报告的 AC 频率 8.3 AC/100 患者年的平均值的 2 倍） ）。方法参数，包括早晨给予糖皮质激素剂量后的皮质醇血浆谱和尿类固醇排泄量、24小时尿类固醇谱、唾液皮质醇谱和头发皮质醇、估计的皮质醇暴露。与个体类固醇敏感性相关的糖皮质激素受体 (NR3C1) 和盐皮质激素受体 (NR3C2) 的多态性（单核苷酸多态性 [SNP]）与 11β-羟基类固醇脱氢酶 1 (HSD11B1) 和 11β-羟基类固醇脱氢酶 2 (HSD11B2) 的 SNP 一起评估。通过血清和尿液电解质和渗透压、血浆肾素浓度和动态血压水平来评估盐皮质激素替代。我们还测量了血浆和尿儿茶酚胺、IL6 和 hsCRP 的血清水平以及 IL6 和 TNF-α 的 SNP。通过问卷调查评估患者对 AC 预防的了解。结果 频繁发生 AC 的患者每日糖皮质激素剂量和头发皮质醇水平较高，而其他研究参数没有显着差异。AC 频率与自我报告的糖皮质激素替代调整的频率呈负相关。结论 尽管皮质醇代谢未受影响，但高危患者较高的糖皮质激素剂量可能与皮质醇敏感性降低或糖皮质激素吸收受损有关。无论生物脆弱性如何，主动剂量调整都显示出对 AC 的保护作用。