Distinctive dynamic adrenal steroid fingerprints in Liver Cirrhosis

초록

Introduction: Adrenal insufficiency is often overestimated when assessed by immunoassay in patients with liver cirrhosis (LC) due to reduced cortisol-binding globulin and hypoalbuminemia, which lower total serum cortisol concentration. Steroid profiling using liquid chromatography tandem mass spectrometry (LC-MS/MS) enables accurate and simultaneous quantification of multiple adrenal steroids. We aimed to characterize serum and salivary adrenal steroid phenotypes in patients with LC compared to non-LC controls using LC-MS/MS methods. Methods: Between 2023 and 2024, patients with LC (n=33) and controls (n=34) were prospectively enrolled, and serum and salivary samples were collected during short Synacthen tests at a single center. LC–MS/MS was applied for the analysis of serum and saliva samples. We measured a panel of 27 serum and 13 salivary steroids, including cortisol (F), cortisone (E), 11β-hydroxy androstenedione (11-OHA4), 11-ketoandrostenedione (11-KA4), and 18-hydroxycorticosterone (18-OHF). Results: Patients with LC had a higher percentage of male (72.7 vs 47.1%, P=.04) and were of similar age (58 vs 60 years, P=.12) than controls. Serum and salivary peak F/E were lower in patients with LC compared to control (serum F/E: 6.40 [5.37-8.11] vs 8.98 [7.25-10.31], P<.001; salivary F/E: 0.25 [0.20-0.34] vs 0.37 [0.24-0.43], P=.043), which indicated decreased 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in LC. In contrast, concentrations of 11-OHA4 (7.29 [5.34-10.02] vs 3.13 [2.18-5.88], P< .001) and 11-KA4 (1.05 [0.69-1.24] vs 0.45 [0.07-0.67], P<.001), which are metabolites of androgen pathways, were higher in patients with LC than in controls. Elevation of 18-OHF (1.08 [0.65-1.59] vs 0.65 [0.45-0.93], P=.001) was observed in patients with LC compared to controls, which may reflect renin-angiotensin-aldosterone system activation secondary to cirrhosis. Conclusions: Patients with LC exhibited a distinctive inactivation of cortisol to cortisone along with an elevation of 11-oxygenated and mineralocorticoid pathway metabolites, indicating cirrhosis -associated remodeling of adrenal steroidogenesis. Accurate diagnosis of adrenal insufficiency in LC requires consideration of cirrhosis-specific alterations of steroid metabolism.