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Serum levels of growth hormone (GH)-dependent peptides could provide important and valuable measures of GH sensitivity and, potentially, responsiveness. In normal individuals, serum insulin-like growth factor I (IGF-I) concentrations are dependent on the dose of GH given, with IGF-I responsiveness not decreasing with age. Individuals heterozygous for the E180 GH receptor (GHR) splice mutation have normal IGF-I generation, but those homozygous for the E180 splice mutation have very low basal and stimulated IGF-I concentrations. Similar results are observed for the serum IGF-binding protein 3 (IGFBP-3) response to GH, with a correlation between changes in serum concentrations of IGF-I and changes in IGFBP-3 in normal, heterozygotic, GH-insensitive and GH-deficient participants. In individuals with the E180 splice mutation, IGF-I and IGFBP-3 tests show sensitivity and specificity for detecting GH insensitivity (GHI). In children with idiopathic short stature, it appears that some individuals have selective resistance to GH, with their ability to generate IGF-I more impaired than their ability to generate other GH-dependent peptides. This heterogeneous group may require individualization of GH dosage. IGF generation tests remain the best short-term, in vivo test for classic GHI, although diagnostic tests will undoubtedly require further modification to identify milder pathophysiologic abnormalities., (Copyright 2004 S. Karger AG, Basel.)

The concept of growth hormone (GH) insensitivity has evolved since the condition was originally identified in 1966, and we now know that the primary defect involved is in the GH receptor. Cloning of the receptor molecule has led to great progress in our understanding of GH insensitivity (GHI) and its therapy, including the roles of GH and insulin-like growth factor I (IGF-I) in growth and development, and the relationships between height and serum levels of GH, IGF-I and their binding proteins. Despite the success of work on GHI and IGF-I, a number of opportunities have been missed in the past. The differences between the metabolic effects of GH and IGF-I are not fully understood, while measurements of IGF-I and IGF-binding protein 3 are perhaps not the ideal means of diagnosing GHI. Finally, the use of IGF-I to treat GHI has a number of limitations, and work is underway to develop alternative therapies., (Copyright 2001 S. Karger AG, Basel)