The effect of 11β-HSD activity on glucocorticoid replacement therapy in secondary adrenal insufficiency with GHD: Based on LC-MS/MS method

Abstract

Abstract Purpose The prognosis of patients with secondary adrenal insufficiency (SAI) receiving long-term glucocorticoid (GC) replacement therapy varies greatly. The reasons behind the phenomenon remain unclear. This study aims to explore whether the heterogeneity of SAI patients’ prognosis was related to change of 11β-HSD activity and the relationship between 11β-HSD1 activity and growth hormone deficiency (GHD).Methods The case-control study included 30 SAI patients with GHD, 20 patients with primary adrenal insufficiency (PAI) and 20 healthy controls (HC). Urinary cortisol/cortisone and their metabolites were analyzed by LC-MS/MS to evaluate the 11β-HSD activity. The 11β-HSD1 activity was evaluated by calculating 5-αTHF + THF/ THE, with a higher ratio, representing a better activity and the 11β-HSD2 activity was evaluated by calculating urinary cortisol/cortisone ratio, which was higher, representing a weaker activity. The differences of 11β-HSD activity were compared among three groups and between different types of GC replacement. The relationship between the activity of 11β-HSD1 and GH/ insulin-like growth factor 1(IGF-1) was analyzed.Results Compared to PAI group, patients in SAI group had lower GC replacement dose(P < 0.001) and higher triceps skinfold thickness and abdominal skinfold thickness (P < 0.01). (5-αTHF + THF) /THE in SAI group was higher than that in PAI and HC groups (P < 0.001). Urinary F/E in PAI group was significantly higher than that in HC group (P < 0.01). There was no linear correlation between 11β-HSD1 activity and GH/IGF-1 levels (r2 =-0.191/0.060, P > 0.05).Conclusion The dose of GC replacement might decrease in SAI patients with GHD based on the augmenting 11β-HSD1 activity.