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Growth hormone has anabolic effects in glucocorticosteroid-dependent children with inflammatory bowel disease: a
Nelly Mauras1, Donald George, Jonathan Evans
1Nemours Children's Clinic, Jacksonville, FL, USA.
Insights
Recombinant human growth hormone (rhGH) improved body composition, bone metabolism, and linear growth in children with inflammatory bowel disease (IBD) on glucocorticosteroids. rhGH counteracted catabolic effects without worsening carbohydrate tolerance.
Area of Science:
- Pediatric Endocrinology
- Metabolic Disorders
- Inflammatory Bowel Disease
Background:
- Glucocorticosteroid therapy in children with inflammatory bowel disease (IBD) can cause catabolic effects, impairing growth.
- Recombinant human growth hormone (rhGH) is being investigated as a potential countermeasure to these side effects.
Purpose of the Study:
- To determine if rhGH can counteract glucocorticosteroid-induced catabolism in children with IBD.
- To assess the safety and efficacy of rhGH in improving linear growth.
- To evaluate the impact of rhGH on disease activity and metabolic parameters.
Main Methods:
- Ten children with IBD on prednisone were treated with rhGH (0.05 mg/kg/day) for 4-12 months.
- Measurements included body composition (DEXA), substrate oxidation, energy expenditure, and growth factors (IGF-I, IGFBP-3).
- Calcium kinetics and bone metabolism markers (bone-specific alkaline phosphatase) were assessed.
Main Results:
- rhGH treatment led to favorable changes in body composition, increasing fat-free mass and decreasing fat mass.
- Linear growth velocity significantly increased from 3.5 cm/yr to 7.7 cm/yr.
- Bone calcium accretion and bone formation markers improved, with no adverse effects on glucose metabolism or IBD activity.
Conclusions:
- rhGH treatment offers beneficial effects on body composition, bone metabolism, and linear growth in prednisone-dependent children with IBD.
- rhGH can counteract some catabolic effects of glucocorticosteroids without compromising carbohydrate tolerance.
- Further research is needed to confirm long-term safety and efficacy.
Abstract:
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.