Patients in critical care can learn more about steroidogenesis and its functional reserves by obtaining a steroid profile and then having their corticotropin levels tested. Here, researchers tested the hypothesis that comparing steroid levels before and after corticotropin stimulation could foretell hospital mortality in sepsis. The results of the randomized, double-blind HYPRESS (Hydrocortisone for Prevention of Septic Shock) experiment in sepsis were analyzed in an exploratory fashion. Patients over 18 with sepsis who were not in shock were enrolled in the study and randomly assigned to receive either a placebo or hydrocortisone. Prior to randomization, both patients and healthy volunteers had corticotropin testing.

The multi-analyte stable isotope dilution method (LC–MS/MS) was used to look at cortisol and the precursors of glucocorticoids (17-OH-progesterone, 11-desoxycortisol) and mineralocorticoids (11-desoxycorticosterone, corticosterone). The results of measurements done on healthy people were used to set reference ranges, and the results of measurements done on placebo patients were used to predict in-hospital mortality. There were corticotropin tests on 180 patients and 20 volunteers. Patients with sepsis had higher levels of 11-desoxycorticosterone and 11-desoxycortisol than healthy people, which shows that both the glucocorticoid and mineralocorticoid pathways were active. After corticotropin stimulation, the cortisol response in 12% of sepsis patients was below normal, and the corticosterone response was below normal in 50% of sepsis patients.

Predicting in-hospital mortality (AUC 0.8, CI 0.70-0.88; sensitivity 83%; specificity 78%) in 90 placebo patients (n=90) with a corticotropin-stimulated cortisol-to-corticosterone ratio greater than 32.2. The probability of developing a shock and the likelihood of dying within 90 days could both be predicted by this ratio. Based on this preliminary research shows that mineralocorticoid steroidogenesis is more commonly reduced in sepsis than glucocorticoid steroidogenesis. The risk of death while hospitalized can be estimated using the ratio of corticotropin-stimulated cortisol to corticosterone.