Relative adrenal insufficiency in cirrhotic patients with ascites (hepatoadrenal syndrome)

Abnormal cholesterol metabolism underlies relative adrenal insufficiency in decompensated cirrhosis

“…Some authors have utilized peak cortisol levels or response to low-dose short synacthen test (instead of delta cortisol levels or SD-SST respectively) and showed a similar prevalence of RAI to our study, yet the prognostic significance of these alternative measures remains unknown. [18][19][20]23,25,31,32 We selected delta cortisol in response to a SD-SST as our definition for RAI a priori for several reasons, including its common use in the literature, the ubiquity of SD-SST administration in clinical practice (including in both the inpatient and outpatient setting) and ease of interpretation. 7,24,28 Furthermore, using a rate of change instead of an absolute baseline or peak cortisol level mitigates some of the underlying impairment in hepatic protein and lipid synthesis seen in subjects with decompensated cirrhosis.…”

“…7,24,28 Furthermore, using a rate of change instead of an absolute baseline or peak cortisol level mitigates some of the underlying impairment in hepatic protein and lipid synthesis seen in subjects with decompensated cirrhosis. [21][22][23][24] Alternative measures of HPA adequacy, such as free cortisol or salivary cortisol levels, have been proposed yet these neither correlate well with serum total cortisol nor have they definitively shown prognostic significance. 20,22,32 Reinforcing this point, free cortisol levels were similar between patients with and without RAI in our study.…”

“…However, approximately 95% of cortisol is bound to hepatically synthesized proteins (primarily, cortisol-binding globulin and albumin), leading to the assumption that total cortisol levels may be falsely low in cirrhosis. [21][22][23][24] Alternative measures of adrenal function, such as serum free cortisol or salivary cortisol, have been proposed, although slow turn-around times and lack of widespread availability have limited their adoption. [22][23][24][25] Furthermore, patient outcomes such as mortality have not yet been shown to correlate with these alternative assays.…”

“…[21][22][23][24] Alternative measures of adrenal function, such as serum free cortisol or salivary cortisol, have been proposed, although slow turn-around times and lack of widespread availability have limited their adoption. [22][23][24][25] Furthermore, patient outcomes such as mortality have not yet been shown to correlate with these alternative assays. 22 Based on the methodological and mechanistic uncertainty surrounding the measurement and development of RAI in decompensated cirrhosis, we sought to provide a more comprehensive framework for clinicians to understand this condition.…”

Liver and Steroid Hormones—Can a Touch of p53 Make a Difference?

“…This is mainly due to their low cholesterol levels and to increased cytokines production such as TNF α, IL-6, IL-1, and endotoxin like lipopolysaccharide, that over stimulate and exhaust the HPA axis (50–53). The accumulating observations of the high prevalence (40–60%) of AI (54) in various stages of cirrhosis suggests that this disease may have a predisposition to AI, which may be a feature of liver disease per se (55–58). Indeed, using “conservative” diagnostic criteria, Marik et al (59) reported a surprisingly high incidence of AI in a large cohort of critically ill patients with liver disease and coined the term “hepatoadrenal syndrome” to describe the association between adrenal dysfunction and liver disease.…”