Insulin-like growth factors and their binding proteins in children born small for gestational age: implication for growth hormone therapy.
The insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are important regulators of growth and metabolism and are the key mediators of the actions of growth hormone (GH). Children born small for gestational age (SGA) have a host of medical problems including an increased risk of poor growth later in life, a tendency to develop metabolic abnormalities and a high incidence of learning disabilities. IGFs and related molecules may be linked to all of these concerns. Mouse models of IGF-I and IGF-II deficiencies have phenotypes reminiscent of human SGA, including slow growth, insulin resistance, and mental dysfunction. Humans with IGF-I mutations are born SGA and exhibit very poor subsequent growth, metabolic syndrome and mental retardation. Current management of children born SGA who present with growth failure during childhood includes treatment with GH. SGA children usually have growth factor levels within the normal range; however, as a group, they display lower IGFBP-3 levels in relation to their IGF-I levels. GH is effective in improving growth in children born SGA, but higher doses of GH are required to achieve optimal outcome, suggesting a component of GH insensitivity in SGA children. As in other indications for GH, a rational monitoring approach (focusing on maintaining IGF levels in the high normal range) is prudent.
Ali
Omar
O
Division of Endocrinology, Department of Pediatrics, Mattel Children's Hospital at UCLA, Los Angeles, Calif. 90095, USA. hassy@mednet.ucla.edu
Cohen
Pinchas
P
D000818:Animals; D002648:Child; D005317:Fetal Growth Retardation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006130:Growth Disorders / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019382:Human Growth Hormone / Q000172:deficiency / Q000627:therapeutic use*; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000502:physiology*; D007333:Insulin Resistance / Q000502:physiology; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics / Q000502:physiology*; D008607:Intellectual Disability / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013002:Somatomedins / Q000235:genetics / Q000502:physiology*
D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins; D019382:Human Growth Hormone