Adrenal insufficiency: Diagnosis in patients with liver cirrhosis is difficult
Authors: Arnaud Galbois, Dominique Thabut
Journal: Journal of Hepatology (2010)

Changes in the 24-h plasma cortisol rhythm in patients with cirrhosisJournal of HepatologyVol. 54Issue 3PreviewTo the Editor: Full-Text PDF Open Access We were very interested by the letter of Montagnese et al. published in this issue of the Journal of Hepatology [[1]Montagnese S. Middleton B. Mani A.R. Skene D.J. Morgan M.Y. Changes in the 24-hour rhythm of cortisol in patients with cirrhosis.J Hepatol. 2011; 54: 588-590Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar]. Many recent publications led us to believe that adrenal insufficiency, assessed by serum total cortisol assays, was very common in patients with liver cirrhosis [2Marik P.E. Gayowski T. Starzl T.E. The hepatoadrenal syndrome: a common yet unrecognized clinical condition.Crit Care Med. 2005; 33: 1254-1259Crossref PubMed Scopus (187) Google Scholar, 3Marik P.E. Adrenal-exhaustion syndrome in patients with liver disease.Inten Care Med. 2006; 32: 275-280Crossref PubMed Scopus (68) Google Scholar, 4Fernandez J. Escorsell A. Zabalza M. Felipe V. Navasa M. Mas A. et al.Adrenal insufficiency in patients with cirrhosis and septic shock: effect of treatment with hydrocortisone on survival.Hepatology. 2006; 44: 1288-1295Crossref PubMed Scopus (235) Google Scholar, 5Tsai M.H. Peng Y.S. Chen Y.C. Liu N.J. Ho Y.P. Fang J.T. et al.Adrenal insufficiency in patients with cirrhosis, severe sepsis and septic shock.Hepatology. 2006; 43: 673-681Crossref PubMed Scopus (235) Google Scholar, 6McDonald J.A. Handelsman D.J. Dilworth P. Conway A.J. McCaughan G.W. Hypothalamic–pituitary adrenal function in end-stage non-alcoholic liver disease.J Gastroenterol Hepatol. 1993; 8: 247-253Crossref PubMed Scopus (55) Google Scholar, 7Zietz B. Lock G. Plach B. Drobnik W. Grossmann J. Scholmerich J. et al.Dysfunction of the hypothalamic–pituitary–glandular axes and relation to child-pugh classification in male patients with alcoholic and virus-related cirrhosis.Eur J Gastroenterol Hepatol. 2003 May; 15: 495-501PubMed Google Scholar]. In fact, cortisol transport proteins (cortisol binding globulin and albumin) are often decreased in patients with cirrhosis, leading to a reduced bound fraction of cortisol, whereas free cortisol concentration, which is the active fraction of cortisol, remains unchanged. We recently showed that serum total cortisol assays (performed at 8 AM before and after a corticotropin injection) largely overestimate adrenal insufficiency prevalence in patients with cirrhosis, especially in those with serum albumin ⩽25 g/L [[8]Galbois A. Rudler M. Massard J. Fulla Y. Bennani A. Bonnefont-Rousselot D. et al.Assessment of adrenal function in cirrhotic patients: salivary cortisol should be preferred.J Hepatol. 2010 Jun; 52: 839-845Abstract Full Text Full Text PDF PubMed Scopus (94) Google Scholar]. Interestingly, Montagnese and colleagues assessed the 24-h rhythm of cortisol in patients with cirrhosis using plasma free cortisol assays, avoiding the bias of the reduced cortisol transport proteins. They report that patients with Child-Pugh B/C cirrhosis have significantly lower plasma free cortisol concentrations and that their rhythms onset and offset are (not significantly) delayed compared to patients with Child-Pugh A cirrhosis. This delay could make the diagnosis of adrenal insufficiency more complicated in patients with severe cirrhosis. In our study, we found that adrenal insufficiency assessed by salivary cortisol (an accurate reflection of free cortisol) was lower than previously reported with serum total cortisol but not rare (8/88: 9.1%) [[8]Galbois A. Rudler M. Massard J. Fulla Y. Bennani A. Bonnefont-Rousselot D. et al.Assessment of adrenal function in cirrhotic patients: salivary cortisol should be preferred.J Hepatol. 2010 Jun; 52: 839-845Abstract Full Text Full Text PDF PubMed Scopus (94) Google Scholar]. All eight patients with adrenal insufficiency were classified as Child-Pugh C. It is unlikely that our results are partly explained by the delayed cortisol rhythm of patients with Child-Pugh B/C cirrhosis highlighted by Montagnese and colleagues. In fact, the maximal plasma free cortisol concentration seems very close to 8 AM in the study of Montagnese, which is the moment when we collected saliva and blood samples to assess cortisol concentrations. These interesting results should be confirmed by a larger study (Montagnese and colleagues included 4 patients with Child-Pugh B and two patients with Child-Pugh C) to determine if this delay has reliable consequences on the diagnosis of adrenal insufficiency in patients with cirrhosis. The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.