Cortisol metabolism in chronic liver disease.
Impairment of cortisol metabolism, evidence of endogenous hypercortism and sensitivity to oral corticosteroids are known to occur in patients with chronic liver disease. Measurements were made of plasma 11-OHCS and urinary cortisol levels and other parameters of adrenal function in a group of such patients. The mean plasma total 11-OHCS was lower in patients than in control subjects, although this difference was not statistically significant and the normal circadian rhythm was maintained. However, in patients with chronic liver disease a greater proportion of the 11-OHCS was in the non-protein bound state resulting in an elevation of this fraction. This elevation of non-protein bound 11-OHCS must represent a resetting of the pituitary-adrenal feedback mechanism in these patients. Corticosteroid binding globulin was lower in patients than in control subjects, although the difference was not statistically significant. Urinary cortisol excretion was significantly reduced as was excretion of 17-ketosteroids. Cortisol secretion rate was found to be normal. It is suggested that elevation of plasma non-protein bound 11-OHCS, resulting from impaired metabolism and reduced protein binding of cortisol in patients with hepatic disease, may explain the features of endogenous hypercorticism seen in such patients. Moreover, in the presence of impaired steroid metabolism and reduced protein binding, these patients may exhibit an increased sensitivity to corticosteroid therapy, and therefore administration of a reduced dosage may be advisable.
D015062:11-Hydroxycorticosteroids / Q000097:blood; D015065:17-Hydroxycorticosteroids / Q000652:urine; D015068:17-Ketosteroids / Q000652:urine; D000293:Adolescent; D000328:Adult; D000368:Aged; D002908:Chronic Disease; D002940:Circadian Rhythm; D005260:Female; D006505:Hepatitis / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism* / Q000652:urine; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D014156:Transcortin / Q000378:metabolism
D015062:11-Hydroxycorticosteroids; D015065:17-Hydroxycorticosteroids; D015068:17-Ketosteroids; D014156:Transcortin; D006854:Hydrocortisone