ESPE Abstracts (2016) 86 RFC4.5

aDepartment of Pediatrics & Pediatric Endocrinology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland; bBioinformatics Knowledge Unit, Lorry I. Lokey Interdisciplinary Center for Life Sciences and Engineering, Technion – Israel Institute of Technology, Haifa, Israel; cSteroid Research & Mass Spectrometry Unit, Division of Pediatric Endocrinology and Diabetology, Center of Child and Adolescent Medicine, Justus Liebig University, Giessen, Germany; dFaculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel

Background: Analysis of steroids by gas chromatography-mass spectrometry (GC-MS) defines a subject’s 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 8.5–18.0 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, Student’s 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.


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