Determination of functional states during sepsis-induced activation of the hypothalamic–pituitary–adrenal (HPA) axis using measurement of ACTH, cortisol, dehydroepiandrosterone-sulfate (DHEAS) and dehydroepiandrosterone (DHEA)

Introduction

Activation of the HPA axis occurs in order to control potentially deleterious effects of systemic inflammation during sepsis. Practically, it is difficult to determine different states of HPA activation since a differing dynamics and individual risk have to be considered.

Methods

Recently, we examined levels of cortisol, DHEAS, DHEA as well as ACTH in 30 patients with severe sepsis (15 survivors, 15 nonsurvivors) and correlated the time course during early and late sepsis to the clinical course and inflammatory markers [1]. Here, we demonstrate and describe different states of HPA activation in characteristic surviving (n = 3) and nonsurviving (n = 3) septic patients of this study by use of hormone and inflammatory profiles.

Results

Four functional states of HPA response with prognostic relevance could be differentiated. I) Activation: infection, systemic inflammation and activation of the HPA axis; high cytokine levels lead to release of ACTH and cortisol. II) Immunogenic stimulation: high cytokine levels maintain cortisol release whereas ACTH is suppressed by high glucocorticoid levels. III) Suppression of inflammation or exhaustion and hyperinflammation, respectively: suppression of inflammation by glucocorticoids or development of relative adrenal insufficiency by adrenal exhaustion resulting in relative hyperinflammation. IV) Recovery or insufficiency, respectively: normalisation of cytokine levels and regeneration of the adrenal driven by normalisation of ACTH. Reconstitution of physiologic ACTH-driven regulation or relative adrenal insufficiency with poor prognosis, respectively.

Discussion

The HPA axis reflects the individual prognostic risk of the patient. The clinical course rarely enables the detection of all time-dependent states of HPA response. For individual diagnostic benefit of hormone measurements in septic patients, rapid availability of hormone levels is necessary.