Dehydroepiandrosterone, dehydroepiandrosterone-sulfate, and cortisol concentrations in intensive care unit patients.

STUDY OBJECTIVE: This purpose of this study was to determine whether severity of illness, as defined by the intensive care unit (ICU) admission APACHE II (updated Acute Physiology and Chronic Health Evaluation) score, is correlated with early morning cortisol, dehydroepiandrosterone (DHEA), and/or dehydroepiandrosterone-sulfate (DHEA-S) concentrations. DESIGN: Early morning concentrations of DHEA, DHEA-S, and cortisol were determined within 24 hrs of admission and compared with admission APACHE II scores. SETTING: Medical (MICU), neurologic (NICU), and surgical (SICU) intensive care units of the University of Pittsburgh Medical Center. PATIENTS: A total of 191 men and women ranging in age from 16 to 93 yrs. All had been admitted to an ICU. MEASUREMENTS AND MAIN RESULTS: Statistically significant correlations between APACHE II scores and cortisol were observed for women in the MICU and SICU (r = .68, p = .0001; r = .35 p = .017, respectively) and for men in the NICU (r = .55, p = .003) and the SICU (r = .29, p = .036). The correlations between APACHE II scores and DHEA concentration data were statistically significant for women in the MICU (r = .37, p = .047) and SICU (r = .43, p = .002), as was the correlation between APACHE II and DHEA-S concentrations among women in the SICU (r = .38, p = .008). Although not statistically significant, a similar relationship was observed in the smaller group of NICU women (r = .40, p = .099). Each correlation was essentially unchanged when adjusted for age. CONCLUSION: These data show a positive correlation between APACHE II and cortisol concentrations in all groups except the MICU men. Also evident is the positive correlation between APACHE II scores and DHEA and DHEA-S concentrations in women, but not in men.

DHEA and DHEA-S: a review.

Dehydroepiandrosterone (DHEA) and its sulfated metabolite DHEA-S are endogenous hormones secreted by the adrenal cortex in response to adrenocorticotrophin (ACTH). Much has been published regarding potential effects on various systems. Despite the identification of DHEA and DHEA-S more than 50 years ago, there is still considerable controversy as to their biological significance. This article reviews the metabolism and physiology of DHEA and DHEA-S, the influence of age and gender on concentrations, and changes in endogenous concentrations associated with disease states and other factors, including diet and exercise. This article is unique in that it also summarizes the influence of drugs on DHEA and DHEA-S concentrations, as well as concentrations of DHEA and DHEA-S observed after the administration of DHEA by various routes. Sections of the article specifically address DHEA and DHEA-S concentrations as they relate to stress, central nervous system function and psychiatric disorders, insulin sensitivity, immunological function, and cardiovascular disorders.

Pharmacokinetics and pharmacodynamics of triazolam after two intermittent doses in obese and normal-weight men.

This study was designed to determine whether differences in alpha-1 acid glycoprotein and free drug concentrations result in an altered response to triazolam. Twelve normal-weight and 12 obese adult male subjects received intravenous doses of triazolam, 0.5 mg, on two occasions separated by 1 week. There was a small difference in the alpha-1 acid glycoprotein concentrations between groups but no difference in free fraction of triazolam. There was a longer terminal half-life (t1/2 beta) in the obese subjects (3.16 +/- 0.87 vs. 3.83 +/- 1.24, p = 0.0098). Overall, week 1 data revealed no difference in effect between normal and obese subjects. However, response data reveal a pattern of increased sensitivity with the second exposure to triazolam. For example, area under the effect curve (AUEC) on all tests was significantly greater in week 2 for both groups of subjects. For a memory test and sedation from 0 to 12 hours, AUEC/free AUC ratios were significantly greater in week 2 for all subjects. The obese had a higher ratio on week 2 than on week 1 for all psychomotor tests and sedation (0 to 4.5 hours; p < 0.05). The results of modeling psychomotor impairment-concentration data pooled by group for each week continue the pattern: week 1 data are similar between the obese and normal-weight subjects. Although EC50 values are up to 15% lower in week 2 for the normal-weight subjects, EC50 values are as much as 66% lower in week 2 for the obese, where a lower EC50 indicates greater sensitivity. Logistic regression of the recognition data is consistent with these results.(ABSTRACT TRUNCATED AT 250 WORDS)