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Abstract

Pharmacological doses of glucocorticosteroids given chronically are associated with a variety of negative side effects which impact the prolonged use of these potent anti-inflammatory agents. They have catabolic effects on protein, resulting in poor tissue healing, an increased incidence of infections and accelerated bone loss. Insulin resistance to both hepatic and peripheral tissues is a common consequence of chronic steroid use, leading at times to impaired carbohydrate metabolism. Steroids affect both the release and the effects of growth hormone (GH) at the target sites, hence becoming functional GH antagonists. When administered to growing children the side effects of glucocorticosteroid treatment are further compounded by a potent and significant suppression of linear growth. Ample experimental and clinical data support a role for GH therapy in counteracting some of the effects of glucocorticosteroids. Using isotope dilution methods we have previously shown that both GH and insulin-like growth factor (IGF)-I can decrease the protein wasting effects of prednisone administration in man. IGF-I has also been shown to enhance type I collagen formation in hydrocortisone-treated human osteoblasts. GH (through IGF-I) significantly enhances linear growth; thus, in states of "functional" GH deficiency, such as that observed in chronic steroid use, GH may also have a potentially beneficial effect. Studies in children on chronic prednisone doses with cystic fibrosis, chronic renal failure or juvenile rheumatoid arthritis have all shown beneficial effects on linear growth after prolonged GH therapy. Data from a recent study of ours using GH in children with steroid-dependent inflammatory bowel disease showed that GH treatment was associated with increased lean body mass, decreased adiposity and increased linear growth. Marked increases in IGF-I concentrations and in kinetic measures of bone calcium accretion (using calcium tracers) were also observed, without any deterioration of disease activity scores or carbohydrate tolerance. In conclusion, GH therapy may play a role in the treatment of children on chronic steroids both as a growth promoting agent and as an anabolic agent on whole body protein and bone. Longer term studies will be needed to better define the safety and efficacy of this approach. Copyright 2001 S. Karger AG, Basel

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Risk of persistent growth impairment after alternate-day prednisone treatment in children with cystic fibrosis.

Nicholas D Allen, James S Fitzsimmons, Anthony P. Farrell … (2000)

It is uncertain whether the growth impairment that occurs in children during long-term treatment with glucocorticoids persists after the medication is discontinued and ultimately affects adult height. We evaluated growth six to seven years after alternate-day treatment with prednisone had been discontinued in 224 children 6 to 14 years of age with cystic fibrosis who had participated in a multicenter trial of this therapy from 1986 through 1991. Of the children, 151 had been randomly assigned to receive prednisone (either 1 or 2 mg per kilogram of body weight) and 73 to receive placebo. We obtained data on growth up to 1997 from the Cystic Fibrosis Foundation Patient Registry and standardized the data to sex- and age-specific norms from the National Center for Health Statistics. We used z scores to compare growth patterns among treatment groups. In 1997, 68 percent of the patients were 18 years of age or older. The z scores for height declined during prednisone therapy; catch-up growth began two years after treatment with prednisone was discontinued. Among the boys, the z scores for height in those treated with prednisone remained lower than the scores for those who received placebo (P=0.02). The mean heights for boys 18 years of age or older were 4 cm less in the prednisone groups than in the placebo group, an equivalent of 13 percentile points (P=0.03). Among the girls, differences in height between those who were treated with prednisone and those who received placebo were no longer present two to three years after prednisone therapy was discontinued. Among children with cystic fibrosis who have received alternate-day treatment with prednisone, boys, but not girls, have persistent growth impairment after treatment is discontinued.