Responsiveness of IGF-I and IGFBP-3 to Therapeutic Intervention in Children and Adolescents with Crohn's Disease

Objective: Abnormal linear growth is common in childhood and adolescent Crohn's disease. We have studied the concentrations of the inflammatory marker CRP and of serum IGF-I and IGFBP-3 in patients with active Crohn's disease and have assessed the changes in these parameters during therapeutic intervention with enteral nutrition or intestinal resection.

Design: Children and adolescents attending the inflammatory bowel disease clinic at our hospital underwent treatment either with enteral nutrition (Study A) or intestinal resection (Study B). These are two separate studies and the results cannot be compared. Serum concentrations of CRP, IGF-I and IGFBP-3 were determined at 0, 2, 8 and 16 weeks after start of enteral nutrition and in addition to height velocity, at 0 and 6 months after intestinal resection.

Subjects: Study A: 14 patients, 9 male, 5 female, median age 12.5 years (range 7.0-17.2), puberty stage 1 (n = 13), stage 3 (n = 1). All had active Crohn's disease. Study B: 9 patients, 7 male, 2 female, median age 13.5 years (range 7.8-16.5), puberty stage 1 (n = 5), stages 2-4 (n = 4). All had Crohn's disease resistant to medical therapy.

Methods: Crohn's disease was confirmed radiologically, endoscopically and histologically. Disease activity was scored using the Lloyd Still index (LSI). Study A: nutritional support was with a polymeric, casein-based formula feed AL 110. Study B: surgical procedures were small bowel resection (n = 2), right hemicolectomy (n = 5), subtotal colectomy (n = 2).

Measurements: Study A: weight SDS, CRP, IGF-1 and IGFBP-3 were measured at 0, 2, 8, 16 weeks after start of enteral feeding. Study B: height velocity, CRP, IGF-I and IGFBP-3 were measured 0, 6 months after intestinal resection.

Statistical Analysis: Medians and ranges were used. Significance of changes was calculated using the Wilcoxon rank test for the analysis of paired data.

Results: Study A: median LSI before treatment was 39 and increased after 8 weeks of enteral nutrition to 60 (P < 0.05). Weight SDS increased at 8 and 16 weeks (P < 0.05) compared to pretreatment. CRP was elevated at 0 weeks, falling during treatment. Median (range) values (normal < 5 mg/l) at 0 at 2, 8, 16 weeks were 53 mg/l (15-150), 8 mg/l (5-25), 7 mg/l (5-83) and 14 mg/l (5-39), all P < 0.001 compared with pretreatment. Median IGF-I-values increased during treatment. Median (range) values at 0, 2, 8, 16 weeks (all P < 0.005) compared to pretreatment, median (range) values at 0, 2, 8, 16 weeks were 78 micrograms/l (50-204), 131 micrograms/l (73-251), 119 micrograms/l (77-291) and 133 micrograms/l (67-497), all P < 0.005 compared to pre-treatment. IGFBP-3 levels increased during treatment. Median (range) values at 0, 2, 8, 16 weeks were 2.4 mg/l (1.4-3.1), 2.9 mg/l (1.8-4.6), 3.0 mg/l, 3.2 mg/l (1.8-4.5), all P < 0.01 compared to pretreatment. Study B: height velocity increased during 6 months after surgery. Median (range) values; 3.3 cm/year (0-8.3) before surgery, 8.4 cm/year (2-12.6) 6 months post-surgery, P < 0.01. Median (range) CRP values fell from 45 mg/l (5-150) to 8 mg/l (5-31) and IGF-I-values increased from 163 micrograms/l (64-286) to 226 micrograms/l (71-391). These changes were not statistically significant. IGFBP-3 values did not change.

Conclusion: The IGF system, as shown by serum IGF-I and IGFBP-3, is responsive to therapeutic intervention in active Crohn's disease. It is likely that a combination of decreased inflammatory activity and improved nutrition contributes to these changes.