Endocrine Abstracts

In severe sepsis circulating DHEA sulfate (DHEAS) has been shown to decrease whilst serum cortisol increases. This has led to the suggestion of an intraadrenal shift from adrenal androgen towards glucocorticoid synthesis in severe stress. Patients with sepsis are therefore assumed to be DHEA deficient and have been suggested to benefit from DHEA replacement. However, only desulfated DHEA is biologically active and DHEAS and DHEA may not freely interconvert as previously thought. Therefore, we have measured serum cortisol, DHEA and DHEAS at baseline and after ACTH stimulation in 184 patients with severe sepsis (121 men, 63 women) and 78 healthy controls (26 men, 52 women). As expected, serum DHEAS was significantly lower in healthy women than men (5.20plus/minus0.37 vs 9.37plus/minus0.86 micromol/l, p<0.001). However, this difference was less pronounced regarding baseline DHEA (31.2plus/minus2.6 vs. 41.9plus/minus4.8 nmol/l, p<0.05) and stimulated DHEA levels did not differ significantly (77.9plus/minus5.5 vs. 82.6plus/minus5.7 nmol/l). Sex-specific differences were conserved in sepsis. Serum cortisol was significantly increased in sepsis (1432plus/minus90 vs. 370plus/minus30 nmol/l, p<0.001) while DHEAS was low. However, desulfated DHEA was significantly increased when compared to healthy controls (m: 97.7plus/minus9.2 vs. 41.9plus/minus4.8 nmol/l, p<0.01; f: 88.2plus/minus10.5 vs. 31.2plus/minus2.6 nmol/l, p<0.001). There was no further increase after ACTH in sepsis whilst controls increased to levels similar to those in sepsis at baseline. This striking discordance between serum DHEA and DHEAS in sepsis resulted in significantly increased DHEA/DHEAS ratios (sepsis vs. normals; m: 45.2plus/minus7.2 vs. 4.7plus/minus0.4; f: 49.2plus/minus8.5 vs. 6.8plus/minus0.5; all p<0.001). Our findings indicate a functional downregulation of DHEA sulfotransferase activity in sepsis, further documenting that circulating DHEAS does not properly reflect the biologically active DHEA pool. These results modify our understanding of adrenal steroid biosynthesis in severe stress and suggest that there is no intraadrenal shift in adrenal steroidogenesis and no need for DHEA replacement in sepsis.