IGF-I assays: current assay methodologies and their limitations.

The diagnosis of disorders of growth hormone (GH) is dependent upon accurate measurement of insulin-like growth factor-I (IGF-I) concentrations since serum IGF-I assays have been found to be useful as a screening tests for the presence of growth hormone deficiency (GHD) in children and in both children and adults they have been found very useful in establishing the diagnosis of acromegaly. IGF-I is also used extensively to monitor the response to GH treatment in children and adults and to monitor the response to treatment in acromegaly. Since IGF-I is influenced by several other hormones and physiologic factors as well as GH, a knowledge of its regulation is essential to understanding how to properly interpret the measurements. Several technical criteria are required for successful laboratory estimation of IGF-I values. These include elimination of interference of IGF-I-binding proteins (IGFBP), utilization of adequate numbers of normal subjects to define the normal ranges and importantly the use of high affinity, high specificity antisera that allow precise and reproducible measurements of the biologically active peptide. Cross comparisons of various commercial assays show that the results generally are similar when values are in the normal range. However, the assays have different performance characteristics when concentrations are either above or below the normal range. To obtain cross laboratory standardization for values outside the normal range requires utilization of similar, high-quality reagents and techniques that are reasonably comparable. Without this degree of standardization, cross comparisons among various reference laboratories are likely to continue to show wide divergence for values that are above or below the 95% confidence interval. A future goal should be the development of standard procedures and reagents that eliminate this degree of variability.