The role of recombinant insulin-like growth factor I in the treatment of the short child

Abstract

Commercial preparations of recombinant human insulin-like growth factor I became available in 2005. Off-label use has been promoted because of the paucity of patients having approved indications; I review the background and rationale for such use. Attempts to identify growth hormone unresponsiveness in children with idiopathic short stature have been nonproductive. Treatment with insulin-like growth factor I for unequivocal growth hormone insensitivity improves but does not correct growth failure, in contrast to the typical experience with growth hormone replacement of growth hormone deficiency. This emphasizes the importance of direct effects of growth hormone at the growth plate, which cannot be duplicated by administration of recombinant insulin-like growth factor I. Adverse effects testify to the more than adequate delivery of administered recombinant human insulin-like growth factor I to other tissues, including lymphoid hyperplasia, coarsening of the facies, and increased body fat. In view of the risk profile, the limited ability of endocrine insulin-like growth factor I to restore normal growth, and the suppression of endogenous growth hormone (and therefore local effects on growth) that occurs with insulin-like growth factor I administration, the use of recombinant insulin-like growth factor I should be limited to those with well-documented growth hormone unresponsiveness and severe short stature.