Dehydroepiandrosterone sulfate and dehydroepiandrosterone sulfate/cortisol ratio in cirrhotic patients with septic shock: another sign of hepatoadrenal syndrome?

Abstract

Background: Cirrhotic patients are susceptible to sepsis and critical illness-related corticosteroid insufficiency (CIRCI). Dehydroepiandrosterone sulfate (DHEAS) is a corticotropin-dependent adrenal androgen, which has immunostimulating and antiglucocorticoid effects. Considering the synchronized synthesis of cortisol and DHEAS and their opposing effects to each other, investigators have proposed measuring these two hormones as a ratio. Severe sepsis has been associated with low DHEAS, especially relative to high cortisol. Despite growing interest in the role of adrenal androgen replacement in critical illness, there have been no data about DHEAS and the DHEAS/cortisol ratio in patients with liver cirrhosis. We studied whether low concentrations of DHEAS and decreased DHEAS/cortisol ratio are associated with poor outcome in patients with liver cirrhosis and septic shock.

Methods: We recruited 46 cirrhotic patients with septic shock, and 46 noncirrhotic counterparts matched by age and sex. We evaluated adrenal function using the short corticotropin stimulation test and analyzed the relation between DHEAS and cortisol.

Results: While the nonsurvivors in the cirrhotic group had significantly lower baseline DHEAS, lower baseline DHEAS/cortisol ratio, and reduced increments of both DHEAS and cortisol upon corticotropin stimulation, the survivors had lower baseline cortisol. Cirrhotic patients with lower DHEAS/cortisol ratio (<1.50) had higher levels of interleukin-6 and tumor necrosis factor alpha, higher Sequential Organ Failure Assessment scores, and higher rates of CIRCI and hospital mortality. Using the area under the receiver operating characteristic (AUROC) curve, both DHEAS and the DHEAS/cortisol ratio demonstrated a good discriminative power for predicting hospital survival (AUROC 0.807 and 0.925 respectively). The cirrhotic group had lower DHEAS and DHEAS/cortisol ratio but higher rates of CIRCI and hospital mortality, compared to the noncirrhotic group.

Conclusions: There is dissociation between cortisol (increased) and DHEAS (decreased) in those cirrhotic patients who succumb to septic shock. Low DHEAS/cortisol ratios are associated with more severe diseases, inflammation, and CIRCI and can serve as a prognostic marker. More investigations are needed to evaluate the role of adrenal androgen in this clinical setting.

Keywords: Adrenal androgen; Cirrhosis; Sepsis; Steroidogenesis.

Fig. 1

Results of SSTs. a Levels of baseline cortisol are significantly higher in nonsurvivors. b Levels of baseline DHEAS are significantly higher in survivors. c Baseline DHEAS/cortisol ratios are significantly higher in survivors. d Cortisol increments upon challenge of ACTH are significantly higher in survivors. e DHEAS increments upon challenge of ACTH are significantly higher in survivors. Results expressed as median, error bars representing the interquartile range, in a, b, d, e. Results expressed as mean, error bars representing the standard deviation, in c. *p < 0.05, **p < 0.01, ***p < 0.001. DHEAS dehydroepiandrosterone sulfate

Fig. 2

a Baseline DHEAS/cortisol ratio is negatively correlated to SOFA score (R = –0.440, p = 0.002). b Baseline DHEAS/cortisol ratio is negatively correlated to IL-6 (R = –0.503, p = 0.005). SOFA Sequential Organ Failure Assessment, DHEAS dehydroepiandrosterone sulfate, IL6 interleukin-6