Dissociation of Serum Dehydroepiandrosterone and Dehydroepiandrosterone Sulfate in Septic Shock

Abstract

Context: Dehydroepiandrosterone (DHEA) replacement in sepsis has been advocated because of the sepsis-associated decrease in serum DHEA sulfate (DHEAS). However, experimental sepsis in rodents leads to down-regulation of DHEA sulfotransferase, which inactivates DHEA to DHEAS, theoretically resulting in higher DHEA levels.Objective: The objective of the study was to test whether serum DHEA and DHEAS are dissociated in septic shock and to determine their association with circulating cortisol in the context of severity of disease and mortality.Design, Setting, and Participants: This was a cross-sectional study consisting of 181 patients with septic shock, 31 patients with acute trauma, and 60 healthy controls.Main Outcome Measures: Serum cortisol, DHEA, and DHEAS were measured before and 60 min after ACTH stimulation.Results: Serum cortisol was increased and DHEAS was decreased in both septic shock and trauma patients (all P Ͻ 0.001). However, compared with healthy controls, DHEA was significantly increased in sepsis but decreased after trauma (all P Ͻ 0.001). In sepsis, neither cortisol nor DHEA increased significantly after ACTH. Most severely ill patients had higher cortisol (P ϭ 0.069) and lower DHEA (P ϭ 0.076) and a significantly higher cortisol to DHEA ratio (P ϭ 0.004). Similarly, the cortisol to DHEA ratio was significantly increased in nonsurvivors of septic shock (P ϭ 0.026), whereas survivors did not differ from controls (P ϭ 0.322). Conclusions:The observed dissociation of DHEA and DHEAS in septic shock contradicts the previous concept of sepsis-associated DHEA deficiency. Increased DHEA levels may maintain the balance between glucocorticoid-and DHEA-mediated immune and vascular effects. However, most severe disease and mortality is associated with an increased cortisol to DHEA ratio, which may represent a novel prognostic marker in septic shock.

Hormonal status in protracted critical illness and in-hospital mortality

“…Increased plasma cortisol level was associated with decreased plasma DHEA and DHEAS levels in men who subsequently died, suggesting adrenal exhaustion [22]. Although the association of mortality with adrenal exhaustion has also been reported previously in septic shock [1,2], we do not have any explanation for the fact that it was observed only in men in the present study. Interestingly, neither high circulating cortisol levels nor adrenal exhaustion were related to the administration of corticosteroids, suggesting that corticosteroid therapy has no deleterious effect on adrenal function.…”

“…Arlt et al . [1] previously showed a lack of association between DHEA (increased) and DHEAS (decreased) and that mortality was associated with an increased cortisol-to-DHEA ratio. However, these results were obtained when patients were in an early stage of septic shock.…”

“…and our study might result from differences in the populations studied, especially with regard to admission diagnosis (sepsis vs. critical illness) and male-to-female sex ratio. The immune system-activating properties of DHEA may account for the association of DHEA levels with mortality [1,2]. These findings would support an assessment of the benefit of DHEA treatment in the postacute phase of critical illness, notably in men [24].…”

“…Critical illness is associated with various endocrinological dysfunctions, which has also been linked to increased mortality, but this association has been reported primarily in acute rather than protracted (>7 days) critical illness [1-4]. As endocrine status changes with the course of critical illness [5], the prognostic value of a given hormone may differ between the acute and prolonged phases.…”

“…Therefore, we assessed the relationships between various endocrine markers and in-hospital mortality in a large population of patients with protracted critical illness [8]. The endocrine functions that we have assessed included the adrenal, thyrotropic, somatotropic and gonadotropic axes, as they have been shown to be impaired during and after critical illness [1-4] and play a major role not only in the response to stress [9,10] but also with regard to patient outcomes [2,3]. These endocrine markers were assessed in a study on ICU-acquired paresis [11] because they affect muscle metabolism.…”