Adrenal insufficiency and liver disease – Re-search

Abstract

patients with end-stage liver disease and raised the quesTo the Editor: It is always a debatable point whether there is much difference between a paper rejected for publication versus the one published but rarely cited. In a recent review on ‘‘Adrenal insufficiency and Liver disease – what is the evidence?” [1] a relevant paper on the topic [2] was ignored by the reviewerswho claimonly 5papers have been published on the topic in the literature. Some 16 years ago, following clinical suspicion of functional adrenal insufficiency in occasional patients with end-stage cirrhosis, we embarked on a systematic study of adrenal function in 51 consecutive adult patients with end-stage non-alcoholic cirrhosis undergoing liver transplant work-up. The study was restricted to those having non-alcoholic liver disease in order to avoid the confounding effects of alcohol on adrenocortical function. Results were compared to 40 healthy controls. Compared with healthy controls, patients 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 the underlying liver disease as assessed by Child-Pugh scores and peak control response to ACTH (r = 0.647,P < 0.0001) and insulin-induced hypoglycaemia (r = 0.597, P < 0.0001). Baseline morning cortisol, free cortisol and dehydroepiandrosterone sulfate levels were unchanged compared with healthy controls. We concluded that hypothalamic–pituitary regulation of adrenal function was significantly blunted in end-stage non-alcoholic liver disease.We postulated that functional adrenal insufficiency might contribute to the mortality of tion of the need for controlled studies of adrenocortical replacement therapy during acute deteriorations (sepsis and haemorrhage) in severe hepatic disease. Thus, it would not seem unreasonable for future authors who tackle this subject to reference this publication. I also feel that the authors should have also have referenced even older studies going back as far as 1957 that seem somewhat relevant to the topic. (These studies are referenced in our paper.) The term ‘‘re-search” is sometimes most apt.