A large percentage of patients with cirrhosis and variceal bleeding will mount an inadequate adrenal response with respect to their condition, and may be classified as having critical illness–related corticosteroid insufficiency, reported Dr. Christos Triantos and his colleagues in the July issue of Clinical Gastroenterology and Hepatology.
Dr. Triantos, of the department of gastroenterology at the University Hospital of Patras, Greece, and his colleagues evaluated 20 patients with cirrhosis and bleeding varices and compared them with 74 controls: 14 healthy volunteers and 60 patients who had stable cirrhosis and no bleeding (Clin. Gastroenterol. Hepatol. 2011 [doi:10.1016/j.cgh.2011.03.033]).
The participants were divided into five groups. Group 1 included 10 with variceal bleeding, who underwent a conventional-dose short synacthen test (SST), administered by injecting a 250-mcg dose of the synthetic adrenocorticotropin hormone synacthen. Serum cortisol concentration was measured at baseline, 30 minutes, and 60 minutes.
Group 2 comprised the remaining 10 patients with variceal bleeding, who underwent the low-dose short synacthen test (LDSST), in which a 1-mcg dose of synacthen was administered. Again, serum cortisol levels were measured at baseline, 30 minutes, and 60 minutes. Two hours later, these patients underwent the SST as well.
Group 3 consisted of the 14 healthy volunteers, who also underwent both tests. Group 4 comprised 50 stable (nonbleeding) cirrhosis patients who underwent the LDSST, and the fifth group comprised the remaining 10 stable cirrhotics, who underwent the SST.
Among nonstressed (nonbleeding) patients who underwent the LDSST, adrenal insufficiency was diagnosed when a peak cortisol level was 18 mcg/dL or less. In stressed (bleeding) patients, the definition of adrenal insufficiency was a peak cortisol level of less than 25 mcg/dL, or a maximum change of less than 9 mcg/dL from baseline.
On the SST, adrenal insufficiency was defined as a peak cortisol level of 18 mcg/dL or less in nonstressed patients. In patients with bleeding, it was a maximum difference between peak and basal levels of less than 9 mcg/dL, or a random total cortisol level of less than 10 mcg/dL.
The authors found that patients with variceal bleeding had higher median basal cortisol levels (15.4 mcg/dL) compared with stable cirrhotic patients (8.7 mcg/dL, P = .001) or healthy volunteers (10.1 mcg/dL, P = .01).
Looking at peak cortisol, patients with bleeding varices also had higher median levels than did nonbleeding cirrhotic patients, both on the SST (32.7 mcg/dL vs. 21 mcg/dL, P = .0001) and on the LDSST (28 mcg/dL vs. 18.5 mcg/dL), although the difference on the latter test did not reach statistical significance.
However, the change between peak and basal values was not significantly different between patients with and without bleeding, either on the SST (15.4 mcg/dL vs. 12.7 mcg/dL, respectively) or the LDSST (9.3 mcg/dL vs. 8.1 mcg/dL).
Overall, "among patients analyzed by SST, 6/20 with variceal bleeding had adrenal insufficiency (AI) (30%), compared with 3/10 controls with [stable] cirrhosis (30%)," wrote the authors.
And on the more sensitive LDSST, "6/10 patients with variceal bleeding had AI (60%) vs. 24/50 controls with cirrhosis (48%)," they added.
The lack of a significant difference between patients with and without bleeding, with regard to the change between peak and basal levels, shows that many of those with bleeding meet the criteria for "critical illness–related corticosteroid insufficiency" with respect to their severity of illness, wrote the authors. None of the healthy volunteers was found to have adrenal insufficiency.
According to the researchers, a large proportion of those with variceal bleeding showed a dysfunctional response on both the SST assay and the more sensitive LDSST test, thought to be a better mimic of physiologic adrenocorticotropic hormone secretion.
"Although better methods of assessing adrenal function in cirrhosis are needed, the clinical significance of the abnormal ACTH tests and [critical illness–related corticosteroid insufficiency] may only be resolved by a clinical trial of corticosteroid supplementation in variceal bleeding as is used in sepsis."
The authors declared no conflicts of interest related to this study.