Growth and Chronic Disease

Abstract

Growth impairment occurs with many chronic conditions. Cystic fibrosis, Crohn’s disease and juvenile idiopathic arthritis are relatively common chronic diseases in childhood associated with substantial growth impairment. While growth failure may be the initial presenting feature of pathology, the pattern of growth is also a useful measure of disease severity and response to treatment. In addition to its diagnostic value, the resulting short stature cannot only be unacceptable to patients but can also have detrimental effects on the physical health of patients with conditions such as cystic fibrosis. Growth impairment in children with chronic disease is associated with disruption of the growth hormone (GH)–insulin-like growth factor (IGF) axis, and predominantly results from undernutrition, chronic inflammation and prolonged corticosteroid treatment. Undernutrition leads to major adaptations in the endocrine system geared towards conserving energy, diverting substrates away from growth and reproduction, and providing alternative sources of energy for critical body homeostasis. Although chronic inflammatory processes exacerbate undernutrition, proinflammatory cytokines such as interleukin-6, tumor necrosis factor-α and interleukin-1β also adversely affect growth, independent of nutrition, by disrupting the integrity of the GH–IGF axis and by direct local effects on growth plate chondrogenesis. These growth-regulating mechanisms are disturbed further by corticosteroids used in some chronic conditions for their anti-inflammatory and immunosuppressive properties. It is likely that the growth-suppressing processes slow growth plate senescence, and this in turn enables catch-up growth on recovery from chronic disease and withdrawal of corticosteroid treatment. Trials of recombinant human GH (rhGH) in patients with growth failure suggest improvement in linear growth as well as beneficial effects on body composition and clinical course. These have been of relatively short duration, and long-term benefits as well as the safety of rhGH need to be evaluated particularly when given concomitantly with corticosteroids.