The measurement of insulin-like growth factor I: clinical applications and significance.

Abstract

Of the somatomedins so far measured, the selective quantitation of insulin-like growth factor I (IGF-I) appears to have the greatest potential in clinical diagnosis. There have been two approaches to the development of immunoassay systems. One type uses antibodies raised against synthetic fragments of IGF-I which exhibit cross-reactivity with the whole hormone. Such assay systems may be adequate for measuring normal adult plasma IGF-I levels, but the potential for the higher sensitivity required for detecting sub-normal plasma levels in young children is apparent only in methods using antibodies raised against the complete hormone. IGF-I in plasma exists as part of a high molecular weight complex in which it is bound to carrier proteins. The binding proteins may interfere with plasma IGF-I measurements by radioligand assays. Direct analysis of untreated plasma samples is claimed to be possible using disequilibrium assay conditions but in order to maximise assay sensitivity it is necessary to employ an initial extraction stage in order to eliminate binding protein interference. Whether the measurement of plasma IGF-I can or should be used in addition to, or as a replacement for, plasma growth hormone (GH) measurement in the clinical assessment of growth disorders remains a controversial issue. Available evidence indicates that a single, random plasma IGF-I level provides an accurate reflection of GH secretion. Adequate discrimination between the elevated levels in acromegaly and normal reference values has been demonstrated. However, in the investigation of growth-retarded children available radioimmunoassay (RIA) methods have proved only partially successful because of the age-related nature of normal plasma IGF-I concentrations. Existing assays appear capable of identifying sub-normal plasma levels after the age of approximately 4 years. In younger subjects an improvement in assay sensitivity is required in order to establish with greater accuracy the relevant normal ranges. Improvements in the identification of the particular lesion responsible for retarded growth in a child can be achieved by measurement of both plasma GH and IGF-I concentrations. The predictive value of the acute plasma IGF-I response to single-dose GH therapy may identify patients who will respond to long-term GH therapy. Better, more informed decisions on subsequent treatment may therefore be made. Apart from GH control, several other factors influence circulating IGF-I levels. Nutritional status can be assessed through reference to IGF-I analysis, overall catabolic or anabolic processes being associated with decreasing or increasing plasma IGF-I levels respectively.