Growth Hormone Therapy in the Glucocorticosteroid-Dependent Child: Metabolic and Linear Growth Effects

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.

A Potent Human C5a Receptor Antagonist Protects against Disease Pathology in a Rat Model of Inflammatory Bowel Disease

“…These drugs, with nonspecific actions, possess numerous side effects, and their chronic use must be used with caution in patients (36,37). In our study, prednisolone pretreatment was effective at reducing the majority of parameters measured, consistent with previous findings (38 -40), although treated rats lost considerable body weight attributed to catabolism, a major side effect with steroid therapy (41,42). Although steroids are widely used in colitis therapy, it is of interest that rats treated with steroid 24 h after the induction of colitis showed no appreciable therapeutic effects.…”

“…This may be explained by the delayed time it takes for steroids to become effective, which may have been too late for any appreciable activity of prednisolone on disease pathology. Alternatively, steroid treatments tend to inhibit natural healing processes associated with disease pathology (41,43).…”

Distinct growth hormone receptor signaling modes regulate skeletal muscle development and insulin sensitivity in mice

“…GH is one of the most important factors that regulates postnatal longitudinal growth, body weight, and body composition in mammals (18,(41)(42)(43)(44)(45). GH exerts anabolic actions in skeletal muscle by both promoting muscle development and facilitating nutrient uptake and utilization in the muscle, thereby coordinating global energy expenditure and body composition (46,47).…”

Growth Hormone Cannot Enhance the Recovery of Dexamethasone-Induced Osteopenia after Withdrawal in Young Female Wistar Rats

“…GH treatment on the GCs-induced osteopenia may increase bone formation and bone mass or density, with a wide range of therapeutic dose (0.1 U/day to 0.5 U/day or more) and duration (1 week to 3 months) Eriksen et al 1993;Slootweg 1993;Vandeweghe et al 1993;Inzucchi and Robbins 1994;Ørtoft et al 1999). Several studies have shown that GH improved the body composition, bone metabolism, and linear growth in the GCs-dependent children (Mauras 2001(Mauras , 2002. Therefore GH has been expected to prevent, treat, or even facilitate the recovery of the GCs-induced osteopenia.…”