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The hypothalamic–pituitary–adrenal axis in critical illness

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Abstract

Hypothalamic-pituitary-adrenal (HPA) axis function is crucial to maintain and restore homeostasis. The HPA axis does not function in isolation. Rather, the HPA axis modulates and reacts to signals from endocrine, neural, and immune systems. Cortisol is the major glucocorticoid secreted by the human adrenal cortex. Its actions are largely mediated by the glucocorticoid receptor. The potent anti-inflammatory actions of glucocorticoids led to their use in critically ill patients. Metaanalyses of these early studies (before 1985) concluded that large glucocorticoid doses had no effect and were potentially detrimental. More recently, the pendulum has swung in the opposite direction based on the concept that critically ill patients may have relative adrenal insufficiency and/or acquired glucocorticoid resistance. However, inconsistent diagnostic criteria, heterogeneity of subjects, variable nutritional status, and pre-existing conditions preclude formulating definitive conclusions regarding glucocorticoid use among critically patients. Diagnosing adrenal insufficiency in the critically ill patient remains challenging. To resolve the issue, our challenge is to develop physiologically relevant tools to assess glucocorticoid action and GR function at the cellular level.

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Authors and Affiliations

  1. Department of Critical Care Medicine, Children’s Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA

    Shekhar Venkataraman & Ricardo Munoz

  2. Division of Pediatric Endocrinology, Department of Pediatrics, Children’s Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, 15213, USA

    Cristina Candido & Selma Feldman Witchel

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  1. Shekhar Venkataraman
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  2. Ricardo Munoz
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  4. Selma Feldman Witchel
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Correspondence to Selma Feldman Witchel.

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Venkataraman, S., Munoz, R., Candido, C. et al. The hypothalamic–pituitary–adrenal axis in critical illness. Rev Endocr Metab Disord 8, 365–373 (2007). https://doi.org/10.1007/s11154-007-9058-9

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