Liver International ISSN 1478-3223
Letters to the Editor DOI:10.1111/liv.12820 Liver Int. 2015; 35: 2202
Relative adrenal insufficiency in patients with cirrhosis and variceal bleeding To the Editor: We read with great interest this study by Graupera et al. (1). The authors prospectively assessed adrenal function in 36 cirrhotic patients with severe acute variceal bleeding (AVB) and 26 non-cirrhotic patients with peptic ulcer bleeding, using the standard-dose short synacthen test (SST) according to a consensus from an international task force of Critical Care (2). The prevalence of relative adrenal insufficiency (RAI) was similar between groups (22 vs. 24%). The major finding of this study was that the probability of survival without further bleeding at 45 days was significantly lower in patients with acute variceal bleeding and RAI than in patients without RAI (25 vs. 68%); however, in the group of patients with ulcer bleeding, RAI was not associated with bleeding outcomes. These interesting results deserve some comments considering that assessment of adrenal function in cirrhosis is difficult. There is no consensus to determine the most sensitive adrenocorticotropic hormone stimulation test in cirrhosis; however, low-dose SST (LDSST) seems to provide a more physiologically relevant stimulus and has greater sensitivity in AI diagnosis compared to SST (3). We have previously showed (4) that the prevalence of RAI in AVB was 60% when using LDSST, but significantly lower (30%) when using SST. The major concern is, however, the use of serum total cortisol to define RAI; in acute stress and cirrhosis the reduced levels of CBG and albumin lead to an overestimation of RAI. Thus, the unbound cortisol fragment or its surrogate, salivary cortisol, can more accurately assess adrenal function in cirrhosis but the diagnostic criteria based on these indices remain to be determined. As we have previously reported (4, 5), Graupera et al. (1) showed that during AVB there is an adrenocortical response to stress; however, this response is inappropriate for the degree of severity of illness (4) and might be related to the worse bleeding-related outcomes of cirrhotic patients with RAI compared to patients without RAI (1). In our previous study (4), which included patients with AVB regardless of the severity of bleeding, no correlation of RAI with bleeding outcomes was
2202
observed; this might reflect that patients with RAI have worse prognosis notably in the setting of severe AVB. Last, we agree with Graupera et al. (1) that the clinical significance of the abnormal adrenal function in AVB needs to be evaluated in a clinical trial using corticosteroid supplementation at least in patients with severe bleeding. Acknowledgements
Financial support: None to be declared. Conflict of interest: The authors do not have any disclosures to report.
Maria Kalafateli and Christos Triantos Department of Gastroenterology, University Hospital of Patras, Patras, Greece
References 1. Graupera I, Pavel O, Hernandez-Gea V, et al. Relative adrenal insufficiency in severe acute variceal and non-variceal bleeding: influence on outcomes. Liver Int 2015; 35: 1964–73. 2. Marik PE, Pastores SM, Annane D, et al. Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine. Crit Care Med 2008; 36: 1937–49. 3. Kazlauskaite R, Evans AT, Villabona CV, et al. Corticotropin tests for hypothalamic-pituitary- adrenal insufficiency: a metaanalysis. J Clin Endocrinol Metab 2008; 93: 4245–53. 4. Triantos CK, Marzigie M, Fede G, et al. Critical illnessrelated corticosteroid insufficiency in patients with cirrhosis and variceal bleeding. Clin Gastroenterol Hepatol 2011; 9: 595–601. 5. Triantos CK, Kalafateli M, Samonakis D, et al. Higher free serum cortisol is associated with worse survival in acute variceal bleeding because of cirrhosis: a prospective study. Eur J Gastro Hepatol 2014; 26: 1125–32.
Liver International (2015) © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Letters to the Editor DOI:10.1111/liv.12820 Liver Int. 2015; 35: 2202
Relative adrenal insufficiency in patients with cirrhosis and variceal bleeding To the Editor: We read with great interest this study by Graupera et al. (1). The authors prospectively assessed adrenal function in 36 cirrhotic patients with severe acute variceal bleeding (AVB) and 26 non-cirrhotic patients with peptic ulcer bleeding, using the standard-dose short synacthen test (SST) according to a consensus from an international task force of Critical Care (2). The prevalence of relative adrenal insufficiency (RAI) was similar between groups (22 vs. 24%). The major finding of this study was that the probability of survival without further bleeding at 45 days was significantly lower in patients with acute variceal bleeding and RAI than in patients without RAI (25 vs. 68%); however, in the group of patients with ulcer bleeding, RAI was not associated with bleeding outcomes. These interesting results deserve some comments considering that assessment of adrenal function in cirrhosis is difficult. There is no consensus to determine the most sensitive adrenocorticotropic hormone stimulation test in cirrhosis; however, low-dose SST (LDSST) seems to provide a more physiologically relevant stimulus and has greater sensitivity in AI diagnosis compared to SST (3). We have previously showed (4) that the prevalence of RAI in AVB was 60% when using LDSST, but significantly lower (30%) when using SST. The major concern is, however, the use of serum total cortisol to define RAI; in acute stress and cirrhosis the reduced levels of CBG and albumin lead to an overestimation of RAI. Thus, the unbound cortisol fragment or its surrogate, salivary cortisol, can more accurately assess adrenal function in cirrhosis but the diagnostic criteria based on these indices remain to be determined. As we have previously reported (4, 5), Graupera et al. (1) showed that during AVB there is an adrenocortical response to stress; however, this response is inappropriate for the degree of severity of illness (4) and might be related to the worse bleeding-related outcomes of cirrhotic patients with RAI compared to patients without RAI (1). In our previous study (4), which included patients with AVB regardless of the severity of bleeding, no correlation of RAI with bleeding outcomes was
2202
observed; this might reflect that patients with RAI have worse prognosis notably in the setting of severe AVB. Last, we agree with Graupera et al. (1) that the clinical significance of the abnormal adrenal function in AVB needs to be evaluated in a clinical trial using corticosteroid supplementation at least in patients with severe bleeding. Acknowledgements
Financial support: None to be declared. Conflict of interest: The authors do not have any disclosures to report.
Maria Kalafateli and Christos Triantos Department of Gastroenterology, University Hospital of Patras, Patras, Greece
References 1. Graupera I, Pavel O, Hernandez-Gea V, et al. Relative adrenal insufficiency in severe acute variceal and non-variceal bleeding: influence on outcomes. Liver Int 2015; 35: 1964–73. 2. Marik PE, Pastores SM, Annane D, et al. Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine. Crit Care Med 2008; 36: 1937–49. 3. Kazlauskaite R, Evans AT, Villabona CV, et al. Corticotropin tests for hypothalamic-pituitary- adrenal insufficiency: a metaanalysis. J Clin Endocrinol Metab 2008; 93: 4245–53. 4. Triantos CK, Marzigie M, Fede G, et al. Critical illnessrelated corticosteroid insufficiency in patients with cirrhosis and variceal bleeding. Clin Gastroenterol Hepatol 2011; 9: 595–601. 5. Triantos CK, Kalafateli M, Samonakis D, et al. Higher free serum cortisol is associated with worse survival in acute variceal bleeding because of cirrhosis: a prospective study. Eur J Gastro Hepatol 2014; 26: 1125–32.
Liver International (2015) © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
