Background: Analysis of steroids by gas chromatography-mass spectrometry (GC-MS) defines a subjects steroidal fingerprint. Here, we compare the steroidal fingerprints of obese children with or without liver disease to identify the steroid metabolomic signature of childhood non-alcoholic fatty liver disease.
Methods: Urinary samples of 85 children (43 girls) age 8.518.0 with obesity (BMI >97%) were quantified for 31 steroid metabolites by GC-MS. The fingerprints of 22 children with liver disease (L1) as assessed by sonographic steatosis (S+) and/or elevated liver enzymes (ALT+), were compared to 63 obese children without markers of liver disease (L0: S− and ALT−). The steroidal signature of the liver disease was generated as a difference of median profiles of L1 and L0 groups.
Results: L1 and L0 children had similar age (mean 14.4 and 14.1 resp.) and z-scored BMI (2.82 and 2.67, resp.). Boys livers were affected more than girls (35.7% and 16.3%, resp.) The steroidal signature of the L1 group was characterized by high glucocorticoids and low androgens, higher 21OHase activity (THE+THF+αTHF)/PT and lower 11β-HSD-I activity (THF+αTHF)/THE (P=0.029, P=0.01, resp, ANOVA) (Fig). Patients with isolated ALT+ presented highest α-Cl concentrations compared to L0 group or patients with only S+ (P=0.03; ANOVA). An/Et ratio as a marker of 5 α-reductase was higher in children with ALT+ compared to ALT- patients (P=0.001, Students two sided t-test).
Conclusions: The steroidal metabolomic signature of liver disease in obese children is characterized by low androgens and highglucocorticoids, impaired 11β-HSD-type I activity, and high 21-hydroxylase and 5α-reductase activity. These findings suggest decreased hepatic degradation of cortisone in liver steatosis, which is compensated for by increased adrenal cortisol generation. It may provide ways for personalized medicine in obese children with liver disease.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology