ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: J Clin Endocrinol Metab. 2017;102:4578-4587

In chronic inflammatory diseases, inflammatory cytokines and exogenous glucocorticoid exposure affect growth through systemic effects on the GH–IGF-1 axis and local effects on the growth plates. Low plasma IGF-1 levels are related to systemic GH insufficiency or to hepatic GH resistance. Changes in IGF binding proteins have also been reported. At the growth plates, cytokines and glucocorticoids suppress chondrocyte proliferation, increase apoptosis, decrease expression of cartilage matrix proteins, and may alter GH and/or IGF-1 signalling (1). Sustained exposure to inflammatory cytokines may have irreversible adverse effects on growth plate chondrogenesis that may explain the partial and inconsistent catch-up growth seen after remission achievement and the weaker growth response to rhGH therapy in patients with long-lasting disease. This study analyzed data collected by 3 prospective clinical trials of rhGH in 58 patients receiving glucocorticoid therapy for systemic or polyarticular Juvenile Idiopathic Arthritis (JIA). rhGH was effective in arresting the decrease in height SDS during the years preceding treatment. Height SDS increased from baseline by a median of 1.0 SD, but rhGH therapy failed to fully restore the genetic growth potential. Overall, the target height was missed by 9 cm and only half had an adult height within their target height. The main determinants of growth outcome were severity of inflammation and age and height at GH initiation. In the authors’ opinion, the disease-related loss of height observed in some forms of JIA, the unpredictable severity of the disease, and the limiting effects of chronic inflammation on the growth response to rhGH support the initiation of therapy as soon as growth deceleration appears, before the growth deficiency becomes severe.

Reference

1. Wong SC, MacRae VE, Gracie JA, McInnes IB, Galea P, Gardner- Medwin J, Ahmed SF. Inflammatory cytokines in juvenile idiopathic arthritis: effects on physical growth and the insulin-like-growth factor axis. Growth Horm IGF Res. 2008; 18: 369–378.