Evidence for Adrenocortical Adaptation to Severe Illness

During serious illness, there are characteristic increases in serum cortisol concentrations and urinary cortisol excretion. In the present studies, we investigated these changes in glucocorticoid metabolism in relation to adrenal androgen metabolism, as measured by RIA of dehydroepiandrosterone (DHA) and DHA sulfate (DHAS). A group of 23 seriously ill men with various disorders, ill for a week or longer, was age-matched to a control group of 25 men, and the following changes were found: 1) basal serum cortisol concentrations were elevated in the ill group (P less than 0.001), 2) basal serum DHA and DHAS concentrations tended to be lower in the ill group (P less than 0.1); 3) basal serum DHA to cortisol and DHAS to cortisol ratios were decreased in the ill group by 80.3% and 77.2%, respectively (P less than 0.001); 4) ACTH-stimulated serum cortisol concentrations increased by the same absolute amount in both groups, whereas the increase in stimulated DHA concentrations in the ill group was 57.2% less (P less than 0.05), indicating a defect in ACTH-stimulated DHA reserve in serious illness; 5) basal daily unconjugated DHA excretion was lower in the ill group (P less than 0.05); (6) basal daily cortisol excretion was higher in the ill group (P less than 0.05); and 7) the basal daily urinary unconjugated DHA to cortisol ratio was 85.4% lower in the ill group (P less than 0.001). Recently, Zipser et al. described the entity of hyperreninemic hypoaldosteronism in the seriously ill. Their findings combined with our own indicate a relative shift in the metabolism of adrenal pregnenolone in serious illness away from mineralocorticoids and adrenal androgens and toward glucocorticoids. The cause of this change is unknown. We speculate that this shift of relative biochemical pathway predominance may be a factor necessary for survival during chronic severe stress.