Hypothalamic-pituitary adrenal function in end-stage non-alcoholic liver disease.
Patients with end-stage liver disease have significant mortality often associated with intercurrent episodes of bleeding or sepsis. Intact adrenal function is essential in such situations. In order to test the hypothesis that adrenal insufficiency might be present in severe liver disease, hypothalamic-pituitary adrenal function was evaluated in patients with end-stage liver disease awaiting transplantation. The study had a prospective, open comparative design with patients restricted to those having non-alcoholic liver disease in order to avoid the confounding direct effects of alcohol on adrenocortical function. Fifty-one consecutive patients with end-stage, non-alcoholic liver disease undergoing evaluation for liver transplantation and 40 healthy controls were studied. Patients who had used corticosteroids (n = 8) or who were unable to complete the investigations (n = 5) were excluded leaving 38 patients eligible for analysis. Adrenal function was evaluated under basal conditions by single morning measurements of plasma total and free cortisol, corticosteroid-binding globulin, dehydroepiandrosterone sulfate and by adrenal stimulation indirectly using insulin-induced (0.1 U/kg, i.v.) hypoglycaemia and/or directly by adrenocorticotrophic hormone (ACTH); 250 micrograms tetracosactrin, i.v.) stimulation. Compared with healthy controls, patients with liver disease had a 64% reduction in maximal increments of plasma cortisol to indirect adrenal stimulation via insulin-induced hypoglycaemia and a 39% reduction to direct adrenal stimulation by ACTH (all P < 0.001). There was a significant negative correlation between the severity of underlying liver disease as assessed by Child-Pugh scores and peak control responses to ACTH (r = -0.647, P < 0.0001) and insulin-induced hypoglycaemia (r = -0.597, P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
McDonald
J A
JA
A. W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
Handelsman
D J
DJ
Dilworth
P
P
Conway
A J
AJ
McCaughan
G W
GW
D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002908:Chronic Disease; D003687:Dehydroepiandrosterone / Q000097:blood; D005260:Female; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D007328:Insulin / Q000494:pharmacology; D008107:Liver Diseases / Q000097:blood / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D013148:Spironolactone / Q000494:pharmacology; D014156:Transcortin / Q000032:analysis
D001786:Blood Glucose; D007328:Insulin; D013148:Spironolactone; D003687:Dehydroepiandrosterone; D000324:Adrenocorticotropic Hormone; D013006:Growth Hormone; D014156:Transcortin; D006854:Hydrocortisone