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Growth and the Growth Hormone-Insulin Like Growth Factor 1 Axis in Children With Chronic Inflammation: Current
S C Wong1, R Dobie1, M A Altowati1
1Developmental Endocrinology Research Group (S.C.W., M.A.A., S.F.A.), University of Glasgow, Royal Hospital for Children, Glasgow G51 4TF, United Kingdom; Division of Developmental Biology (R.D., C.F.), Roslin Institute, University of Edinburgh, Midlothian EH25 9RG, United Kingdom; and Hormone Research (G.A.W.), Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia.
Insights
Children with chronic inflammatory diseases often experience growth failure. Recombinant human growth hormone (GH) shows promise for improving growth, but more long-term data are needed.
Area of Science:
- Pediatric Endocrinology
- Inflammatory Diseases
- Growth Disorders
Background:
- Chronic inflammatory conditions like juvenile idiopathic arthritis, inflammatory bowel disease, and cystic fibrosis frequently cause growth failure and delayed puberty in children.
- Proinflammatory cytokines, glucocorticoid use, and poor nutrition disrupt the GH-IGF axis and growth plate function, impairing linear growth.
- Understanding cytokine and glucocorticoid effects on the growth plate is crucial for developing effective growth promotion strategies.
Purpose of the Study:
- To comprehensively review growth abnormalities in children with juvenile idiopathic arthritis, inflammatory bowel disease, and cystic fibrosis.
- To examine systemic abnormalities of the GH-IGF axis and growth plate perturbations in these conditions.
- To systematically review studies on recombinant human GH and discuss the role of recombinant human IGF-1 in managing growth failure.
Main Methods:
- Literature review of growth abnormalities in specific chronic inflammatory conditions.
- Systematic review of published studies on recombinant human GH therapy.
- Discussion of the role of recombinant human IGF-1 in growth promotion.
Main Results:
- Children with chronic inflammatory diseases exhibit significant growth failure and pubertal abnormalities.
- Biological therapies targeting cytokines may improve growth in some children, but approximately one-third show limited response.
- Recombinant human GH demonstrates potential for partial catch-up growth, though long-term outcomes require further investigation.
Conclusions:
- Growth failure in chronic inflammatory conditions is multifactorial, involving hormonal axes and local growth plate mechanisms.
- While biological therapies offer some benefit, recombinant human GH presents a promising therapeutic option for improving growth.
- Further long-term studies are essential to fully elucidate the efficacy and safety of GH and IGF-1 therapies in these pediatric populations.
Abstract:
Growth failure is frequently encountered in children with chronic inflammatory conditions like juvenile idiopathic arthritis, inflammatory bowel disease, and cystic fibrosis. Delayed puberty and attenuated pubertal growth spurt are often seen during adolescence. The underlying inflammatory state mediated by proinflammatory cytokines, prolonged use of glucocorticoid, and suboptimal nutrition contribute to growth failure and pubertal abnormalities. These factors can impair growth by their effects on the GH-IGF axis and also directly at the level of the growth plate via alterations in chondrogenesis and local growth factor signaling. Recent studies on the impact of cytokines and glucocorticoid on the growth plate further advanced our understanding of growth failure in chronic disease and provided a biological rationale of growth promotion. Targeting cytokines using biological therapy may lead to improvement of growth in some of these children, but approximately one-third continue to grow slowly. There is increasing evidence that the use of relatively high-dose recombinant human GH may lead to partial catch-up growth in chronic inflammatory conditions, although long-term follow-up data are currently limited. In this review, we comprehensively review the growth abnormalities in children with juvenile idiopathic arthritis, inflammatory bowel disease, and cystic fibrosis, systemic abnormalities of the GH-IGF axis, and growth plate perturbations. We also systematically reviewed all the current published studies of recombinant human GH in these conditions and discussed the role of recombinant human IGF-1.
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