Abstract

Critical illness is hallmarked by major changes in all hypothalamic–pituitary–peripheral hormonal axes. Extensive animal and human studies have identified a biphasic pattern in circulating pituitary and peripheral hormone levels throughout critical illness by analogy with the fasting state. In the acute phase of critical illness, following a deleterious event, rapid neuroendocrine changes try to direct the human body toward a catabolic state to ensure provision of elementary energy sources, whereas costly anabolic processes are postponed. Thanks to new technologies and improvements in critical care, the majority of patients survive the acute insult and recover within a week. However, an important part of patients admitted to the ICU fail to recover sufficiently, and a prolonged phase of critical illness sets in. This prolonged phase of critical illness is characterized by a uniform suppression of the hypothalamic–pituitary–peripheral hormonal axes. Whereas the alterations in hormonal levels during the first hours and days after the onset of critical illness are evolutionary selected and are likely beneficial for survival, endocrine changes in prolonged critically ill patients could be harmful and may hamper recovery. Most studies investigating the substitution of peripheral hormones or strategies to overcome resistance to anabolic stimuli failed to show benefit for morbidity and mortality. Research on treatment with selected and combined hypothalamic hormones has shown promising results. Well-controlled RCTs to corroborate these findings are needed.

Highlights

  • Critical illness is defined as the presence of acute, lifethreatening organ dysfunction requiring vital organ support and can be evoked by major trauma, extensive surgery, large-scale burn injuries and severe medical diseases

  • A significant number of patients admitted to the ICU fail to recover sufficiently within a few days and enter a more prolonged phase of critical illness, known as ‘chronic critical illness’ [1]

  • Only for patients with a prolonged ICU stay, adrenal atrophy and suppressed adrenocorticotropic hormone (ACTH)-regulated gene expression was documented postmortem [58]. Whether these long stay patients would benefit from treatment with ACTH infusion, over exogenous glucocorticoids, in analogy with what has been described for the thyroidal axis should be investigated in future studies

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Summary

Introduction

Critical illness is defined as the presence of acute, lifethreatening organ dysfunction requiring vital organ support and can be evoked by major trauma, extensive surgery, large-scale burn injuries and severe medical diseases. A hallmark of critical illness, is the immediate initiation of multiple physiologic processes in an attempt to rebalance the complex dynamic equilibrium, commonly known as homeostasis This so-called ‘stress response’ comprises many tightly controlled neural and endocrine adaptations to provide sufficient energy and hemodynamic stability to survive and overcome the immediate phase after onset of critical illness. The hypothalamus, the major control center of the different neuroendocrine axes, gains a complex set of sensory input from a variety of internal and external stimuli This collection of information together with the input of endocrine feedback loops triggers the hypothalamus to produce and secrete tropic hormones in the hypophyseal portal system mainly targeting the anterior pituitary. We will review the anterior pituitary function and the five main neuroendocrine axes during health and critical illness, both in the acute and the chronic phase

The somatotropic axis during health
The somatotropic axis during critical illness
The thyroid axis during health
The thyroid axis during critical illness
The adrenal axis during health
The adrenal axis during critical illness
The lactotropic axis during health
The lactotropic axis during critical illness
The gonadal axis during health
The gonadal axis during critical illness
Central feedback inhibition
Nutritional signals
Average levels during health
Findings
Acute phase Prolonged phase Critical illness
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