Growth hormone has anabolic effects in glucocorticosteroid-dependent children with inflammatory bowel disease: a pilot study.
The present studies were designed to determine whether recombinant human growth hormone (rhGH) can counteract some of the catabolic effects of glucocorticosteroid therapy in children chronically treated with glucocorticosteroids. Whether rhGH can safely improve short-term linear growth was also investigated. The effect of rhGH on disease activity was also assessed. Ten children (6 boys, 4 girls) with inflammatory bowel disease (IBD) on oral prednisone for at least 4 months prior to these studies were recruited (mean +/- SE, 11.9 +/- 0.9 years). Leucine and glucose isotope studies, body composition, substrate oxidation and energy expenditure rates, and growth factors were measured at baseline (D1) and at 4 months after treatment with rhGH (0.05 mg/ kg. d subcutaneously [SC]) while continuing oral prednisone. Dual-emission x-ray absorptiometry (DEXA) and calcium kinetic analysis ((42)Ca/(46)Ca) were performed also. rhGH was continued for 6 months to assess linear growth in all 10 subjects, 7 of whom continued rhGH for 12 months. Body composition changed favorably with increased fat free mass (+3 kg, P =.001) and decreased percent fat mass (-3.5%, P =.001) after 4 months of treatment. Rates of whole body protein turnover, oxidation, and synthesis remained invariant, with no changes in substrate oxidation or resting energy expenditure rates. Linear growth velocity increased from 3.5 +/- 0.4 cm/yr when the patients were treated with prednisone only, to 7.7 +/- 0.9 after 6 months of combined prednisone/rhGH (P =.001). The growth velocity was sustained in the 7 patients treated with rhGH for 12 months. Plasma insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) concentrations also increased significantly while on rhGH treatment. No changes in calcium absorption were observed but there was a significant increase in kinetic rates of bone calcium accretion (P =.045) as well as in bone-specific alkaline phosphatase concentrations, a measure of bone formation (P =.03). Fasting and 2-hour postprandial glucose concentrations, fasting insulin levels, and HbA(1C) were invariant during combined rhGH/prednisone treatment. The Crohn's disease activity score was unchanged with rhGH therapy. In summary, rhGH treatment of corticosteroid-dependent patients with IBD was associated with positive changes in body composition, bone metabolism, and linear growth, without deterioration of carbohydrate tolerance or intermediate metabolism of substrates. We conclude that treatment with rhGH has beneficial effects in prednisone-dependent growing children. Larger studies will be needed to assess the long-term safety and efficacy of this approach.
Mauras
Nelly
N
Nemours Children's Clinic, Jacksonville, FL, USA.
George
Donald
D
Evans
Jonathan
J
Milov
David
D
Abrams
Steven
S
Rini
Annie
A
Welch
Susan
S
Haymond
Morey W
MW
D000293:Adolescent; D000596:Amino Acids / Q000097:blood; D001823:Body Composition; D001842:Bone and Bones / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D050260:Carbohydrate Metabolism; D002648:Child; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006128:Growth / Q000187:drug effects; D006133:Growth Substances / Q000097:blood; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D007700:Kinetics; D008297:Male; D010084:Oxidation-Reduction; D010865:Pilot Projects; D011241:Prednisone / Q000627:therapeutic use*; D014176:Protein Biosynthesis; D011994:Recombinant Proteins / Q000627:therapeutic use; D012449:Safety; D012720:Severity of Illness Index
D000596:Amino Acids; D005938:Glucocorticoids; D006133:Growth Substances; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D002118:Calcium; D011241:Prednisone