The Insulin-Like Growth Factor I Generation Test in Adults

Abstract

The insulin-like growth factor I (IGF-I) generation test has the potential to assess the ability of an individual to respond to an acute bolus of growth hormone (GH), in terms of IGF-I, IGF-binding protein 3 and acid-labile subunit responses. This article will discuss something of the history of the IGF-I generation test, and review some of the major studies to date. The IGF-I generation test was first used in adults by Lieberman et al., who studied the effects of ageing and oestrogen administration, and suggested that decreased responsiveness to GH occurs with increasing age and oral oestrogen administration. Our results, however, show that, while activity of the GH/IGF-I axis declines with age, peripheral responsiveness to GH is not affected. As in the Lieberman study, we found that oral oestrogen replacement reduces responses of GH-dependent peptides to GH stimulation in healthy post-menopausal women. Transdermal oestrogen administration also reduced responsiveness to GH, although to a lesser degree than orally administered oestrogen. In addition, utilizing a non-weight-based dose of GH we have demonstrated that obese individuals produce greater increases in IGF-I following an acute bolus of GH. In GH deficiency (GHD), data suggesting enhanced peripheral responsiveness should be interpreted with caution, and with awareness of differences between these groups in terms of age and obesity. The IGF-I generation test may allow a fresh approach to unanswered questions in the field of GHD, but as the IGF-I response to GH is not strictly associated with protein anabolism or clinical benefit, the question remains whether this test will predict the effect of longer-term GH administration.