Abstract：
OBJECTIVE: This study aims to identify susceptibility markers for adrenal crises (AC) in educated patients with chronic adrenal insufficiency (AI).
METHODS: 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.
CONCLUSIONS: 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.
METHODS: 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.
CONCLUSIONS: 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.
摘要：
目的：本研究旨在确定受过教育的慢性肾上腺功能不全（AI）患者肾上腺危象（AC）的易感标志物。
方法：一项涉及66例AI患者的病例对照研究，分析糖皮质激素和盐皮质激素暴露的影响，肾上腺髓质功能,炎症参数，以及交流频率的教育状况。根据AC发生率将患者分为低（n=32）和高（n=34）AC频率组（低于或高于先前前瞻性研究中报告的8.3AC/100患者年的平均AC频率2倍）。
方法：参数，包括早晨糖皮质激素剂量给药后的皮质醇血浆概况和尿类固醇排泄，24小时尿类固醇分析，唾液皮质醇分析,和头发皮质醇，估计皮质醇暴露量。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。通过血清和尿电解质和渗透压评估盐皮质激素替代，血浆肾素浓度，和动态血压水平。我们还测量了血浆和尿儿茶酚胺，血清IL6和hsCRP水平，以及IL6和TNF-α的SNP。通过问卷调查评估患者对AC预防知识的了解。
结果：频繁的AC患者每天的糖皮质激素剂量和头发皮质醇水平较高，研究的其他参数没有显着差异。AC频率与自我报告的糖皮质激素替代调整的频率成反比。
结论：高危患者的糖皮质激素剂量较高，尽管皮质醇代谢没有受到影响,可能与皮质醇敏感性降低或糖皮质激素吸收受损有关。预发剂量调整显示出对AC的保护作用，不管生物的脆弱性。
方法：一项涉及66例AI患者的病例对照研究，分析糖皮质激素和盐皮质激素暴露的影响，肾上腺髓质功能,炎症参数，以及交流频率的教育状况。根据AC发生率将患者分为低（n=32）和高（n=34）AC频率组（低于或高于先前前瞻性研究中报告的8.3AC/100患者年的平均AC频率2倍）。
方法：参数，包括早晨糖皮质激素剂量给药后的皮质醇血浆概况和尿类固醇排泄，24小时尿类固醇分析，唾液皮质醇分析,和头发皮质醇，估计皮质醇暴露量。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。通过血清和尿电解质和渗透压评估盐皮质激素替代，血浆肾素浓度，和动态血压水平。我们还测量了血浆和尿儿茶酚胺，血清IL6和hsCRP水平，以及IL6和TNF-α的SNP。通过问卷调查评估患者对AC预防知识的了解。
结果：频繁的AC患者每天的糖皮质激素剂量和头发皮质醇水平较高，研究的其他参数没有显着差异。AC频率与自我报告的糖皮质激素替代调整的频率成反比。
结论：高危患者的糖皮质激素剂量较高，尽管皮质醇代谢没有受到影响,可能与皮质醇敏感性降低或糖皮质激素吸收受损有关。预发剂量调整显示出对AC的保护作用，不管生物的脆弱性。
