The Royal Free Sheila Sherlock Liver Centre and University Department of Surgery, University College London and Royal Free Hospital, London, United Kingdom; Department of Clinical and Molecular Biomedicine, University of Catania, Garibaldi Hospital, Catania, Italy.
Department of Clinical and Molecular Biomedicine, University of Catania, Garibaldi Hospital, Catania, Italy.
Clin Gastroenterol Hepatol. 2014 Mar;12(3):504-12.e8; quiz e23-4. doi: 10.1016/j.cgh.2013.08.028. Epub 2013 Aug 24.
BACKGROUND & AIMS: Measurements of serum levels of total cortisol can overestimate the prevalence of adrenal dysfunction in patients with cirrhosis because they have low concentrations of corticosteroid-binding globulin and albumin. We used measurements of serum total cortisol and serum free cortisol after the low-dose short Synacthen test (LDSST) to assess adrenal dysfunction.
We studied 79 patients with stable cirrhosis; adrenal dysfunction was defined by peak concentrations of total cortisol ≤494 mmol/L and/or peak concentrations of free cortisol ≤33 nmol/L after the LDSST. We determined free cortisol index (FCI) scores and calculated free cortisol levels by using Coolens' equation. The Cox regression model was used to assess the relationship between adrenal dysfunction and outcomes (death or liver transplant).
On the basis of measurement of total cortisol, 34% of patients had adrenal dysfunction, and on the basis of measurement of free cortisol, 29% had adrenal dysfunction. There was agreement between total cortisol and free cortisol levels in 22% of patients; in 13%, adrenal dysfunction was diagnosed only on the basis of total cortisol and in 6% only on the basis of free cortisol (κ coefficient, 0.56; P < .01). Low concentrations of corticosteroid-binding globulin (21 vs 54 μg/mL, P < .01) led to an overestimation of adrenal dysfunction that was based on measurement of total cortisol. Measurements of calculated free cortisol constantly overestimated free cortisol concentrations, with variations as large as 87% for baseline values and up to 84% after stimulation. Adrenal insufficiency, defined by FCI scores <12, was detected in 30% of patients; among them, 23% also had subnormal peak levels of free cortisol (κ coefficient, 0.70; P < .001). Adrenal dysfunction was not significantly associated with patient outcomes, on the basis of Cox model analysis.
Adrenal insufficiency, defined by LDSST, is frequent in patients with stable cirrhosis, on the basis of measurements of total and free cortisol. FCI scores are better than measurement of total cortisol in assessing adrenal function in patients with cirrhosis. We did not associate adrenal dysfunction with outcome, but further studies are needed.
由于肝硬化患者皮质类固醇结合球蛋白和白蛋白浓度较低，血清总皮质醇水平的测量可能会高估肾上腺功能障碍的患病率。我们使用小剂量短 Synacthen 试验（LDSST）后血清总皮质醇和血清游离皮质醇的测量来评估肾上腺功能障碍。
我们研究了 79 例稳定的肝硬化患者；肾上腺功能障碍的定义为 LDSST 后总皮质醇峰值浓度≤494μmol/L 和/或游离皮质醇峰值浓度≤33nmol/L。我们测定了游离皮质醇指数（FCI）评分，并使用 Coolens 方程计算了游离皮质醇水平。Cox 回归模型用于评估肾上腺功能障碍与结局（死亡或肝移植）之间的关系。
根据总皮质醇测量，34%的患者存在肾上腺功能障碍，根据游离皮质醇测量，29%的患者存在肾上腺功能障碍。在 22%的患者中，总皮质醇和游离皮质醇水平之间存在一致性；在 13%的患者中，仅根据总皮质醇诊断出肾上腺功能障碍，在 6%的患者中仅根据游离皮质醇诊断出（κ 系数，0.56；P<.01）。皮质类固醇结合球蛋白浓度较低（21 与 54μg/ml，P<.01）导致基于总皮质醇测量的肾上腺功能障碍的高估。计算的游离皮质醇的测量始终高估了游离皮质醇浓度，基础值的变化高达 87%，刺激后高达 84%。FCI 评分<12 定义为肾上腺功能不全，在 30%的患者中检测到；其中，23%的患者游离皮质醇峰值水平也低于正常值（κ 系数，0.70；P<.001）。根据 Cox 模型分析，肾上腺功能障碍与患者结局无显著相关性。
根据 LDSST，在稳定的肝硬化患者中，基于总皮质醇和游离皮质醇的测量，肾上腺功能不全很常见。FCI 评分比测量皮质醇更能评估肝硬化患者的肾上腺功能。我们没有将肾上腺功能障碍与结局联系起来，但需要进一步研究。
