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Reduced cortisol in acute liver failure is not due to pituitary failure or reduced binding proteins

Reduced cortisol is common in patients with acute liver failure (ALF). The aetiology of this phenomenon is unclear, relating potentially to reduced levels of cortisol binding proteins, pituitary or adrenal dysfunction. We examined the relative importance of these factors.


Twenty patients with ALF, admitted to a 10 bedded specialist liver intensive care unit, were investigated. We sampled blood at 9:00 a.m. and measured total cortisol, ACTH and the two main binding proteins CBG and albumin as well as standard biochemistry. Cholesterol was measured as precursor of cortisol synthesis. From these data, the unbound cortisol was calculated. Normal ranges are: cortisol > 250 nmol/l, CBG 39.7 ± 6.3 μg/l for males and 42.2 ± 5.6 μg/l for females, ACTH 39 pg/ ml (range <25–65), albumin 35–50 g/l. Absolute values are given as median and interquartile range. Comparisons were performed using the Mann-Whitney U test and correlations using the Spearman Rank Correlation coefficient.


All patients had CBG below the normal range (BNR) and albumin was BNR in 19/20 patients. Fifty percent of patients had a total cortisol BNR all of whom also had a free cortisol BNR. All patients with normal cortisol had normal free cortisol. Cholesterol, albumin, and CBG were all significantly lower in patients with cortisol BNR (Table). The CBG was significantly correlated with total cortisol (R = 0.519, P < 0.05). ACTH is above normal range in 18/20 patients and was higher in those with cortisol above 250 nmol/l (Table).

Table 1


In ALF, reduced total cortisol is accompanied by reduced free cortisol despite reduced CBG and albumin. The ACTH results suggest adrenal dysfunction rather than pituitary failure as the cause of the reduction in total cortisol seen in these critically ill patients. The low cholesterol in those with suboptimal cortisol levels may suggest lack of this precursor is of importance and requires further study.

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Harry, R., Auzinger, G. & Wendon, J. Reduced cortisol in acute liver failure is not due to pituitary failure or reduced binding proteins. Crit Care 6 (Suppl 1), P221 (2002).

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