Corticosteroids Increase Protein Breakdown and Loss in Newly Diagnosed Pediatric Crohn Disease

Abstract

Children with Crohn disease have altered growth and body composition. Previous studies have demonstrated decreased protein breakdown after either corticosteroid or anti-TNF-␣ therapy. The aim of this study was to evaluate whole body protein metabolism during corticosteroid therapy in children with newly diagnosed Crohn disease. Children with suspected Crohn disease and children with abdominal symptoms not consistent with Crohn disease underwent outpatient metabolic assessment. Patients diagnosed with Crohn disease and prescribed corticosteroid therapy returned in 2 wk for repeat metabolic assessment. Using the stable isotopes [d5] phenylalanine, [1-13 C] leucine, and [ 15 N 2 ] urea, protein kinetics were determined in the fasting state. Thirty-one children (18 controls and 13 newly diagnosed with Crohn disease) completed the study. There were no significant differences in protein breakdown or loss between patients with Crohn disease at diagnosis and controls. After corticosteroid therapy in patients with Crohn disease, the rates of appearance of phenylalanine (32%) and leucine (26%) increased significantly, reflecting increased protein breakdown, and the rate of appearance of urea also increased significantly (273%), reflecting increased protein loss. Whole body protein breakdown and loss increased significantly after 2 wk of corticosteroid therapy in children with newly diagnosed Crohn disease, which may have profound effects on body composition. (Pediatr Res 70: 484-488, 2011) C hildren with Crohn disease suffer from growth impairment before diagnosis, and despite therapy, continue to have growth difficulties which may persist to altered adult growth outcomes. At diagnosis, these children suffer from not only linear growth impairment but also deficits in lean body mass (1) and bone mineral density (2). These deficits may result from altered nutritional intake, malabsorption, and inflammation. A prospective observational study demonstrated increases in BMI and fat mass in the 2 y after diagnosis of pediatric Crohn disease; however, no significant change in lean body mass and persistent deficits in bone mineral content were observed (2). Emerging evidence suggests gender differences in body composition may exist in pediatric patients with Crohn disease. Females with Crohn disease may have more persistent lean body mass deficits than males (3). Current therapeutic strategies may not be resulting in significant and important improvements in lean body mass in these patients.Both malnutrition and inflammation may be observed in pediatric patients with Crohn disease, and they may have opposing effects on substrate metabolism. In patients with chronic malnutrition, there are marked reductions in whole body protein turnover (4), including protein synthesis and breakdown, and in urea excretion, a marker of protein loss (5). In these patients, adaptations to reduction in protein intake result in minimization of protein loss. However, inflammation leads to increased whole body protein metabolism. Injection of T...

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