Intensive Care Medicine

, Volume 41, Issue 1, pp 131–133 | Cite as

Understanding the HPA response to critical illness: novel insights with clinical implications

  • Eva Boonen
  • Greet Van den Berghe
Understanding the Disease

The stress response, essential for life during health and disease, is governed by the hypothalamus–pituitary–adrenal (HPA) axis. It starts by hypothalamic CRH release which, via the hypophyseal portal system, activates the corticotrophs in the anterior pituitary gland to secrete ACTH. ACTH stimulates steroidogenesis by binding to the melanocortin-2 receptor on adrenocortical cells. ACTH upregulates expression of this receptor and mediates cholesterol release from lipid droplets while activating expression of genes encoding proteins for cholesterol uptake and synthesis [1, 2, 3, 4, 5]. ACTH also increases expression of genes encoding key steroidogenic enzymes [1, 2, 3, 4, 5]. Besides this feedforward activation of cortisol secretion, feedback inhibition of CRH and ACTH by cortisol occurs at the pituitary and hypothalamic level.

Within this classical stress response concept, the hypercortisolemia of critical illness is thought to be brought about by elevated circulating ACTH which...


Critical Illness Cortisol Production Plasma Cortisol Concentration Relative Adrenal Insufficiency Plasma ACTH Level 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Supported by the Fund for Scientific Research Flanders, Belgium (FWO G.0417.12 to GVdB); by the Methusalem Program of the Flemish Government to GVdB via the KU Leuven University (METH/08/07) and by an ERC Advanced grant (AdvG-2012-321670) to GVdB from the Ideas Program of the European Union 7th framework program.

Conflicts of interest

Nothing to declare.


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Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2014

Authors and Affiliations

  1. 1.Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular MedicineKU Leuven UniversityLeuvenBelgium

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