Abnormal cholesterol metabolism underlies relative adrenal insufficiency in decompensated cirrhosis.

BACKGROUND & AIMS: Relative adrenal insufficiency (RAI) in patients with cirrhosis is associated with increased mortality. Although the pathogenesis of RAI remains unclear, disordered cholesterol metabolism may contribute.

METHODS: We performed a prospective cohort study of 96 non-critically ill subjects with decompensated cirrhosis at a tertiary care center. Subjects were administered 250µcg cosyntropin, with RAI defined as an increase in total cortisol < 9 µg/dL. High-density lipoprotein (HDL) levels and serum cholesterol esterification percentage (%CE), a validated surrogate marker of lecithin-cholesterol acyltransferase (LCAT) activity, were measured to assess the relationship between disordered cholesterol metabolism and the presence of RAI. Subjects were followed until death, liver transplantation, or a maximum of 6 months.

RESULTS: Subjects with RAI had decreased levels of HDL (18 vs. 29 mg/dL, p <0.01) and %CE (64% vs. 66%, p = 0.03). Correlation was seen between HDL and %CE (r = 0.7, R2 = 0.49; p < 0.01) and each integer decrease in %CE predicted an approximately 2% increase in the probability of RAI. Transplant-free survival was reduced in subjects with RAI at both 6 months (43% vs. 71%, p = 0.01) and 90 days (54% vs. 81%, p < 0.01).

CONCLUSIONS: Disruption in cholesterol metabolism contributes to the development of RAI in cirrhosis, as decreased LCAT activity leads to reduced HDL trafficking to the adrenal gland.