ESPE Abstracts (2016) 86 P-P2-56

The Effect of Anti-TNF on the Metabolism of Adrenal Hormones; A Steroid Metabolomic Approach

Ariel Keinana, Michaela F. Hartmannc, Yonatan Butbula,b, Stefan A. Wudyc & Dov Tiosanoa,b

aRambam Medical Center, Haifa, Israel; bThe Technion – Israel Institute of Technology, Haifa, Israel; cSteroid Research and Mass Spectrometry Unit, Division of Pediatric Endocrinology and Diabetology, Center of Child and Adolescent Medicine, Justus-Liebig University, Giessen, Germany

Background: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease seen in children. The systemic features of JIA are mediated by cytokine products of an activated immune system. Recent studies showed that the median level of urine cortisol in active JIA patients is significantly lower than remission period and control groups.

Objective and hypotheses: One of the najor drugs in JIA is TNFα blocker (Enbrel). The aim of the study was to evaluate adrenal metabolaites production and adrenal enzymatic activity by using urine GC-MS analysis before and after Enbrel.

Method: Eleven JIA patients were enrolled into the study, eight female and three male, age 12±6.2 years (range 3–21 years). The average disease duration was 6.3±5.2 years (range 1.6–18 years) and the duration of Enbrel reatment was 3±2.8 years (range 6 months to 10 years). The patients were treated once weekly with Enbrel injection (0.8 mg/kg). Age and sex-matched healthy controls were matched to each patient. Patients were not treated with corticosteroids in the preceding 3 months.

Results: Of the 35 metabolites measured, 23 were significantly lower in JIA patients before Enbrel treatment compared to healthy control group. One day after the injection 30 metabolites normalized and were similar to the control group. only five metabolites were lower in the JIA patients. We did not fined significant differences in the metabolites ratios that reflects changes in the enzymatic activity. The most significant reduction in JIA patients were 17OH pregnenolone metamolites.

Conclusion: Perior to Enbral treatment almost all adrenal metabolites in the urine are significatly low mainly due to the active inflamatory proces. Immidiatly after the treatment many matabolaites raised to normal valalues as found in the contol group. We could not fined differences in metabolites ratios that reflects changes in adrenal enzymes activity. Blocking TNFα imidiatly restors adrenal function in JIA.

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