Growth retardation in chronic diseases: possible mechanisms.

Multiple and complex mechanisms are likely to be involved in producing the growth retardation that occurs in children with chronic disease. The principal mechanisms in the pathway leading to growth arrest include too little substrate available to the child, excessive need for and over-consumption of substrate, and inefficient management of body components needed for growth. It is proposed that alterations in the growth hormone (GH)-insulin-like growth factor (IGF) system play a major role at each of the steps between insult from chronic disease and growth retardation. When substrate is insufficient, the production and action of IGF-I are attenuated at multiple points in the GH-IGF cascade. When over-consumption of substrate occurs, a situation of 'internal starvation' probably develops--leading to events similar to those that take place when substrate supply is inadequate. Finally, conditions that cause inefficient management of body components needed for growth, as characterized by increased proteolysis, appear to be attenuated by GH and IGF-I.