Reduced cortisol metabolism during critical illness.
Reduced cortisol metabolism during critical illness.
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DOI：
10.1056/nejmoa1214969
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发表时间：
2013-04-18
期刊：
影响因子：
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通讯作者：
Van den Berghe G
中科院分区：
文献类型：
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作者：
Boonen E;Vervenne H;Meersseman P;Andrew R;Mortier L;Declercq PE;Vanwijngaerden YM;Spriet I;Wouters PJ;Vander Perre S;Langouche L;Vanhorebeek I;Walker BR;Van den Berghe G
危重病通常伴有高皮质醇血症，这是由于应激诱导的下丘脑-垂体-肾上腺轴激活。然而，在危重患者中也有低促肾上腺皮质激素水平的报道，这可能是由于皮质醇代谢降低。在重症监护病房的158名患者和64名对照组中，我们测试了皮质醇代谢的五个方面：促肾上腺皮质激素和皮质醇的每日水平;血浆皮质醇清除率，代谢和在输注氘标记的类固醇激素作为示踪剂期间的产生; 100 mg氢化可的松的血浆清除率;尿皮质醇代谢物水平;以及肝脏和脂肪组织中信使RNA和蛋白质的水平，以评估主要的皮质醇代谢酶。总的和游离的循环皮质醇水平在患者中始终高于对照组，而促肾上腺皮质激素水平则低于对照组（两组比较P<0.001）。皮质醇的产生在患者中高出83%（P=0.02）。在示踪剂输注期间和给予患者100 mg氢化可的松后，皮质醇清除率降低超过50%（两项比较均P≤0.03）。与对照组相比，所有这些因素导致患者血浆皮质醇水平增加3.5倍（P<0.001）。受损的皮质醇清除率也与对促肾上腺皮质激素刺激的皮质醇反应较低相关。皮质醇代谢降低与肝脏和肾脏中皮质醇失活减少相关，如尿类固醇比率、示踪剂动力学和肝脏活检样本评估所示（所有比较P≤0.004）。在危重病期间，皮质醇分解减少，与皮质醇代谢酶的表达和活性受到抑制有关，导致高皮质醇血症，从而导致促肾上腺皮质激素抑制。对重症患者的诊断和治疗意义尚不清楚。（由比利时科学研究基金会和其他机构资助; ClinicalTrials.gov编号，NCT 00512122和NCT 00115479;当前对照试验编号，ISRCTN 49433936，ISRCTN 49306926和ISRCTN 08083905。
Critical illness is often accompanied by hypercortisolemia, which has been attributed to stress-induced activation of the hypothalamic–pituitary–adrenal axis. However, low corticotropin levels have also been reported in critically ill patients, which may be due to reduced cortisol metabolism. In a total of 158 patients in the intensive care unit and 64 matched controls, we tested five aspects of cortisol metabolism: daily levels of corticotropin and cortisol; plasma cortisol clearance, metabolism, and production during infusion of deuterium-labeled steroid hormones as tracers; plasma clearance of 100 mg of hydrocortisone; levels of urinary cortisol metabolites; and levels of messenger RNA and protein in liver and adipose tissue, to assess major cortisol-metabolizing enzymes. Total and free circulating cortisol levels were consistently higher in the patients than in controls, whereas corticotropin levels were lower (P<0.001 for both comparisons). Cortisol production was 83% higher in the patients (P=0.02). There was a reduction of more than 50% in cortisol clearance during tracer infusion and after the administration of 100 mg of hydrocortisone in the patients (P≤0.03 for both comparisons). All these factors accounted for an increase by a factor of 3.5 in plasma cortisol levels in the patients, as compared with controls (P<0.001). Impaired cortisol clearance also correlated with a lower cortisol response to corticotropin stimulation. Reduced cortisol metabolism was associated with reduced inactivation of cortisol in the liver and kidney, as suggested by urinary steroid ratios, tracer kinetics, and assessment of liver-biopsy samples (P≤0.004 for all comparisons). During critical illness, reduced cortisol breakdown, related to suppressed expression and activity of cortisol-metabolizing enzymes, contributed to hypercortisolemia and hence corticotropin suppression. The diagnostic and therapeutic implications for critically ill patients are unknown. (Funded by the Belgian Fund for Scientific Research and others; ClinicalTrials.gov numbers, NCT00512122 and NCT00115479; and Current Controlled Trials numbers, ISRCTN49433936, ISRCTN49306926, and ISRCTN08083905.)