Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, 40138 Bologna, Italy.
Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy.
Eur J Endocrinol. 2024 Mar 30;190(4):327-337. doi: 10.1093/ejendo/lvae037.
Various glucocorticoid replacement therapies (GRTs) are available for adrenal insufficiency (AI). However, their effectiveness in restoring glucocorticoid rhythm and exposure lacks adequate biochemical markers. We described the diurnal salivary cortisol (SalF) and cortisone (SalE) rhythm among different GRTs and analysed the associations between saliva-derived parameters and life quality questionnaires.
Control subjects (CSs, n = 28) and AI patients receiving hydrocortisone (HC, n = 9), cortisone acetate (CA, n = 23), and dual-release hydrocortisone once (DRHC-od, n = 10) and twice a day (DRHC-td, n = 6) collected 9 saliva samples from 07:00 to 23:00. Patients compiled Pittsburgh Sleep Quality Index, Hospital Anxiety and Depression Scale, and Addison disease-specific quality-of-life questionnaires. SalE and SalF were measured by liquid chromatography-mass spectrometry. Exposure was monitored using SalE for HC and DRHC and SalF for CA. Area under the curve (AUC) was computed. Different GRTs were compared by Z-scores calculated from saliva-derived parameters. Questionnaire results predictors were evaluated with multiple regression analysis.
Compared with controls, all GRTs resulted in glucocorticoid overexposure in the morning. Hydrocortisone, CA, and DRHC-td caused overexposure also in afternoon and evening. Compared with other treatments, CA determined increased Z-score-07:00 (P < .001), DRHC-td determined increased Z-score-AUC07:00→14:00 (P = .007), and DRHC-od induced lower Z-score-AUC14:00→23:00 (P = .015). Z-scores-AUC14:00→16:00 ≥ .619 best predicted questionnaire scores.
None of the GRTs mimics normal glucocorticoid rhythmicity and exposure. SalE, SalF, and Z-score may be useful markers for monitoring and comparing different GRTs. Excess glucocorticoid in early afternoon best associated with depressive symptoms and worse life and sleep quality.
各种糖皮质激素替代疗法（GRT）可用于治疗肾上腺功能不全（AI）。然而，它们在恢复糖皮质激素节律和暴露方面的有效性缺乏足够的生化标志物。我们描述了不同 GRT 下的日间唾液皮质醇（SalF）和皮质酮（SalE）节律，并分析了唾液衍生参数与生活质量问卷之间的关系。
对照组（CSs，n = 28）和接受氢化可的松（HC，n = 9）、醋酸可的松（CA，n = 23）、每日一次双释放氢化可的松（DRHC-od，n = 10）和每日两次双释放氢化可的松（DRHC-td，n = 6）的 AI 患者，从 07:00 到 23:00 采集 9 份唾液样本。患者填写匹兹堡睡眠质量指数、医院焦虑抑郁量表和艾迪生病生活质量问卷。通过液相色谱-质谱法测量 SalE 和 SalF。使用 SalE 监测 HC 和 DRHC 的暴露情况，使用 SalF 监测 CA 的暴露情况。计算曲线下面积（AUC）。通过从唾液衍生参数计算的 Z 分数比较不同的 GRT。使用多元回归分析评估问卷结果预测因子。
与对照组相比，所有 GRT 均导致糖皮质激素在早上过度暴露。HC、CA 和 DRHC-td 也导致下午和晚上过度暴露。与其他治疗相比，CA 导致 07:00 的 Z 分数增加（P <.001），DRHC-td 导致 07:00→14:00 的 AUC07:00 的 Z 分数增加（P =.007），而 DRHC-od 导致 14:00→23:00 的 AUC 降低（P =.015）。Z 分数-AUC14:00→16:00 ≥.619 最佳预测问卷评分。
没有一种 GRT 能模拟正常的糖皮质激素节律和暴露。SalE、SalF 和 Z 分数可能是监测和比较不同 GRT 的有用标志物。下午早些时候的糖皮质激素过多与抑郁症状以及较差的生活和睡眠质量最相关。
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