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Endocrine aspects of acute and prolonged critical illness

Nature Clinical Practice Endocrinology & Metabolism volume 2, pages 20–31 (2006)Cite this article

Abstract

Critical illness is characterized by striking alterations in the hypothalamic–anterior-pituitary–peripheral-hormone axes, the severity of which is associated with a high risk of morbidity and mortality. Most attempts to correct hormone balance have been shown ineffective or even harmful because of a lack of pathophysiologic insight. There is a biphasic (neuro)endocrine response to critical illness. The acute phase is characterized by an actively secreting pituitary, but the concentrations of most peripheral effector hormones are low, partly due to the development of target-organ resistance. In contrast, in prolonged critical illness, uniform (predominantly hypothalamic) suppression of the (neuro)endocrine axes contributes to the low serum levels of the respective target-organ hormones. The adaptations in the acute phase are considered to be beneficial for short-term survival. In the chronic phase, however, the observed (neuro)endocrine alterations appear to contribute to the general wasting syndrome. With the exception of intensive insulin therapy, and perhaps hydrocortisone administration for a subgroup of patients, no hormonal intervention has proven to beneficially affect outcome. The combined administration of hypothalamic releasing factors does, however, hold promise as a safe therapy to reverse the (neuro)endocrine and metabolic abnormalities of prolonged critical illness by concomitant reactivation of the different anterior-pituitary axes.

Key Points

  • The (neuro)endocrine responses to acute and prolonged critical illness are substantially different; in the acute phase, the adaptations are probably beneficial in the struggle for short-term survival, whereas the chronic alterations participate in the wasting syndrome of prolonged critical illness and can be maladaptive

  • Thorough understanding of the pathophysiology underlying endocrine disturbances in critical illness is of vital importance when considering new therapeutic strategies to correct these abnormalities; indeed, the choice of hormone and corresponding dosage are crucial and lack of insight has been shown to be dangerous.

  • In contrast to the classic dogma that stress-induced hyperglycemia is beneficial to organs that largely rely on glucose for energy supply but do not require insulin for glucose uptake, it is now clear that the development of hyperglycemia is an important risk factor in terms of mortality and morbidity of critically ill patients; importantly, strict blood glucose control with intensive insulin therapy improves survival and largely prevents several critical-illness-induced complications

  • A remarkable interaction has been demonstrated among the different (neuro)endocrine axes; the concomitant administration of several hypothalamic releasing factors holds promise as an effective and safe intervention to jointly restore the corresponding axes and to counteract the hypercatabolic state of prolonged critical illness

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Figure 1: Response of the somatotropic axis to critical illness.
Figure 2: Effects of a growth-hormone secretagogue on the somatotropic axis in prolonged critical illness.
Figure 3: Response of the thyroid axis to critical illness.
Figure 4: Effects of thyrotropin-releasing hormone and a growth-hormone secretagogue on the thyroid axis in prolonged critical illness.
Figure 5: Simplified concept of the pituitary-dependent changes during the course of critical illness.

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Acknowledgements

The work was supported by research grants from the Catholic University of Leuven (OT/03/56) and the Fund for Scientific Research (FWO), Flanders, Belgium (G.0278.03). Ilse Vanhorebeek and Lies Langouche are Postdoctoral Fellows of the FWO, Flanders, Belgium.

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  1. Ilse Vanhorebeek, Lies Langouche & Greet Van den Berghe

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  1. Ilse Vanhorebeek
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Correspondence to Greet Van den Berghe.

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G Van den Berghe holds an unrestrictive Catholic University of Leuven Novo Nordisk Chair of Research.

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Vanhorebeek, I., Langouche, L. & Van den Berghe, G. Endocrine aspects of acute and prolonged critical illness. Nat Rev Endocrinol 2, 20–31 (2006). https://doi.org/10.1038/ncpendmet0071

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