Berghe G Van den
Acta Clin Belg. 2014 Dec;69(6):397-406. doi: 10.1179/2295333714Y.0000000093.
Critical illness represents a major challenge for the human body, implicating that an adequate stress response is indispensable for survival. Therefore, for a long time, activation of the hypothalamic pituitary adrenal axis was assumed to be increased to respond to this stressful situation. Recent novel insights, however, provided evidence that the HPA-axis is regulated differently during critical illness. Cortisol metabolism was shown to be reduced which contributed to hypercortisolism in an energy efficient way without increasing cortisol production dramatically. Yet, the concomitant low ACTH levels, explained by negative feedback inhibition, could lead to an understimulation of the adrenal gland and affect adrenal structure and function, given the crucial role of ACTH for adrenal gland maintenance. This side-effect could negatively affect outcome predominantly in the prolonged phase of critical illness and could explain the increased incidence of adrenal failure in these patients. Altogether, novel findings represent a paradigm shift in our current understanding of HPA-axis regulation during critical illness and redirect future research perspectives with an urgent need to well-designed clinical trials to further explore HPA-axis functioning during critical illness.
危重病对人体来说是一项重大挑战，这意味着适当的应激反应对生存至关重要。因此，长期以来，人们认为下丘脑-垂体-肾上腺轴的激活会增加，以应对这种应激情况。然而，最近的新见解表明，危重病期间下丘脑-垂体-肾上腺轴的调节方式有所不同。研究表明，皮质醇代谢降低，这以一种节能的方式导致皮质醇增多症，而不会大幅增加皮质醇的产生。然而，由于负反馈抑制导致的促肾上腺皮质激素水平同时降低，鉴于促肾上腺皮质激素对肾上腺维持的关键作用，可能会导致肾上腺刺激不足，并影响肾上腺的结构和功能。这种副作用主要在危重病的延长阶段可能对预后产生负面影响，并可以解释这些患者肾上腺功能不全发生率的增加。总之，新发现代表了我们目前对危重病期间下丘脑-垂体-肾上腺轴调节理解的范式转变，并重新引导未来的研究方向，迫切需要精心设计的临床试验来进一步探索危重病期间下丘脑-垂体-肾上腺轴的功能。
