Growth hormone (GH) and glutamine (GLN) therapy in children with refractory short bowel syndrome (SBS) who underwent intestinal lenghening procedures (ILP)

Abstract

INTRODUCTION: SBS in children is characterized by severe malabsorption following massive small intestinal resection. ILP has been performed in children who fail to wean from Parenteral Nutrition (PN). Although ILP is associated with increased intestinal tolerance, most patients remain PN-dependent. Intestinal absorption has improved in adults with refractory SBS utilizing GH and the gut-trophic amino acid GLN. Some adults have discontinued PN with this therapy. GH may act via insulin-like growth factorI(IGF-I) to stimulate morphologic and functional adaptation. GLN is the primary fuel for small intestinal cells and may become depleted in catabolic states. GLN supplementation attenuates PN-induced mucosal atrophy in rats. PURPOSE: This feasibility study assessed whether the combination of GH and GLN modifies nutrient absorption in children who underwent intestinal resections in infancy followed by ILP. PATIENTS AND METHODS: Pt#1 was an 8yo with SBS secondary to gastroschisis and volvulus. He had 30 cm of residual duodenum following ILP. He required PN daily for normal growth despite gastrostomy-tube feedings of 1440 calories/day. Pt#2 was a 7 yo who had SBS secondary to multiple atresias. She had ajejuno-ileal segment of 80 cm. following ILP. She had been PN-dependent, but the central line was removed following an episode of candidal sepsis 4 months prior to enrollment. G-tube was placed for enteral feedings. Baseline absorption studies were obtained at entry. Children were then treated with GH (0.1 mg/kg/day sc) and GLN (0.5 gm/kg/day enterally) for 3 months. Enteral feedings were not modified. Absorption studies were repeated at 1 and 3 months after initiating therapy. Laboratory evaluation included fat and protein absorption, and plasma IGF-I levels. Body composition was measured by DEXA. RESULTS: The percent of fat absorption was 90% in Pt#1 and 80% in Pt#2 prior to treatment. This decreased to 78% in Pt#1 and was maintained at 84% in Pt#2 following treatment. The percent of intestinal nitrogen absorption did not improve in Pt #1 whereas Pt#2 demonstrated a gradual improvement during the treatment period (0-time=34%, I-month=45%, and 3-months=49%). Treatment resulted in an increase in proportion of lean body mass from 70 to 86% in pt#1 and 92 to 94% in pt#2. Additionally, serum IGF-I levels increased 3-fold in pt#1 and 10-fold in pt#2. CONCLUSION: Combined GH and GLN treatment was well tolerated in children with SBS. Variable effects on gut nutrient absorption and body composition may be a function of the length and type of residual bowel and/or IGF-I response to treatment. Further studies using this treatment in children are suggested. This research was funded by Genentech Foundation for Growth and Development, Charlottesville, VA.