Effect of Recombinant Human Growth Hormone on Intestinal Absorption and Body Composition in Children With Short Bowel Syndrome

Abstract

This prospective study aimed to establish the effect of recombinant human growth hormone (rhGH) on intestinal function in children with short bowel syndrome (SBS). Eight children with neonatal SBS were included. All were dependent on parenteral nutrition (PN) for >3 years (range, 3.8-11.6 years), with PN providing >50% of recommended dietary allowance for age (range, 50%-65%). The subjects received rhGH (Humatrope) 0.13 mg/kg/d subcutaneously over a 12-week period. The follow-up was continued over a 12-month period after rhGH discontinuation. Clinical and biological assessments were performed at baseline, at the end of the treatment period, and 12 months after the end of treatment. No side effects related to rhGH were observed. PN requirements were decreased in all children during the course of rhGH treatment. Between baseline and the end of treatment, significant increases were observed in concentrations (mean ± standard deviation) of serum insulin-like growth factor 1 (103.1 ± 49.9 µg/L vs 153.5 ± 82.2 µg/L; P < .01), serum insulin-like growth factor-binding protein 3 (1.7 ± 0.6 mg/L vs 2.5 ± 0.9 mg/L; P < .001), and plasma citrulline (16.5 ± 14.8 µmol/L vs 25.2 ± 18.3 µmol/L; P < .05). A median 54% increase in enteral intake (range, 10%-244%) was observed (P < .001) and net energy balance improved significantly (P < .002). It was necessary for 6 children to be maintained on PN or restarted after discontinuation of rhGH treatment, and they remained on PN until the end of the follow-up period. A 12-week high-dose rhGH treatment allowed patients to decrease PN, but only 2 patients could be definitively weaned from PN. Indications and cost-effectiveness of rhGH treatment for SBS pediatric patients need further evaluation.

Growth Hormone to Improve Short Bowel Syndrome Intestinal Autonomy

“…[36][37][38] The same modifications of body composition were recently reported in children. 27 Despite weight loss during GH treatment, our patients did not develop clinical malnutrition or biological indicators of nutrition deficiency, as described in a previous adult study. 18 In children, the high rate of discontinuation of PN obtained by Goulet et al may be due in part to a more intensive weaning off of PN than in our study.…”

“…13,17 In children, Goulet et al obtained a high rate of successful PN weaning off (6 of 8 patients) after 12 weeks of highdose GH. 27 These discrepancies may be the consequence of cohort differences in the degree of PN dependence or differences in study designs, especially in treatments associated with the GH, such as the administration of glutamine, a special diet (eg, high-carborhydrate, low-fat diet; ad libitum diet), or increasing enteral support. It could be argued that the combination of GH with glutamine and a modified diet could be more effective in decreasing PN dependence than GH alone.…”

Short-Bowel Syndrome in Children — An Update in Management Strategies

“…Laboratory studies have shown that GH causes mucosal hyperplasia and increases the adaptive capacity after small resection [83,84]. Other actions of GH include enhancement of the villus height and crypt depth, positive nitrogen balance and bowel growth when rats were given GH combined with glutamine and/or a diet high in protein [85,86].Studies in children with PSBS showed a reduction in PN [87], but after cessation of GH the positive response could not be preserved [88)]. The results in adults are controversial.…”

Current Status of Intestinal Failure and Intestinal Transplantation

“…Cholestyramine often improves diarrhea associated with bile salt malabsorption. In parenteral nutrition dependent patients with SBS, the use of recombinant human growth hormone has led to variable results [34,35]. More recently, the focus has shifted to glucagon-like peptide 2 and its analogues (Teduglutide) as a strategy to regulate maintenance and adaptive growth of the small intestinal mucosa.…”