However, low corticotropin levels have also been reported in critically ill patients, which may be due to reduced cortisol metabolism.
METHODS
In a total of 158 patients in the intensive care unit and 64 matched controls, we tested five aspects of cortisol metabolism: daily levels of corticotropin and cortisol; plasma cortisol clearance, metabolism, and production during infusion of deuterium-labeled steroid hormones as tracers; plasma clearance of 100 mg of hydrocortisone; levels of urinary cortisol metabolites; and levels
of messenger RNA and protein in liver and adipose tissue, to assess major cortisol-metabolizing enzymes.
RESULTS
Total and free circulating DNA/RNA Synthesis inhibitor cortisol levels were consistently higher in the patients than in controls, whereas corticotropin levels were lower (P<0.001 for both comparisons). Cortisol production was 83% higher in the patients (P=0.02). There was a reduction of more than 50% in cortisol clearance during tracer
infusion and after the administration of 100 mg of hydrocortisone in the patients (P <= 0.03 for both comparisons). All these factors accounted for an increase by a factor of 3.5 in plasma cortisol levels in the patients, as compared with controls (P<0.001). Impaired cortisol clearance also correlated with a lower cortisol response to corticotropin
stimulation. Reduced cortisol metabolism Z-IETD-FMK purchase was associated with reduced inactivation of cortisol in the liver and kidney, as suggested unless by urinary steroid ratios, tracer kinetics, and assessment of liver-biopsy samples (P <= 0.004 for all comparisons).
CONCLUSIONS
During critical illness, reduced cortisol breakdown, related to suppressed expression and activity of cortisol-metabolizing enzymes, contributed to hypercortisolemia and hence corticotropin suppression. The diagnostic and therapeutic implications for critically ill patients are unknown. (Funded by the Belgian Fund for Scientific Research and others; ClinicalTrials.gov numbers, NCT00512122 and NCT00115479; and Current Controlled Trials numbers, ISRCTN49433936, ISRCTN49306926, and ISRCTN08083905.)”
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