Determinants of circulating insulin-like growth factor-I

Total IGF-I level in serum is a sensitive index during growth hormone (GH) replacement therapy of adults, since GH stimulates the hepatic expressions of both insulin-like growth factor (IGF-I) and acid-labile subunit (ALS) and the major part of IGF-I in the circulation is found in a ternary complex together with ALS and IGFBP-3. However, other regulators of the proteins constituting the ternary complex may influence IGF-I levels. In healthy subjects the serum IGF-I levels are low at birth, rise during childhood, with peak levels during puberty, and decline with increasing age. This pattern has been attributed to the age-dependent GH production, but it is unknown whether the wide range of IGF-I levels within each age interval is due to GH production or GH sensitivity. In elderly twins approximately 60% of IGF-I levels are genetically determined. The remaining environmental dependency of IGF-I is partly due to nutrition. Both caloric and protein content of the diet is of importance. Thus, low IGF-I levels are found in GH deficient patients as well as in patients with GH resistance due to malnutrition or GH receptor defects. It is essential that IGF-I determination is performed by assays in which IGFBPs do not interfere, and that IGF-I concentration is evaluated in relation to age, i.e. expressed in SD score, and the number of individuals constituting the reference intervals improves the sensitivity and specificity. Although determination of IGF-I is recommended in assessing GH deficiency in children, its diagnostic value in patients with adult onset of GH deficiency is not agreed upon. In the age group above 40-80 years many patients with pituitary/hypothalamic disorders and GH peaks below 3 microg/l during provocation tests have normal IGF-I levels. It is not clarified, whether the IGF-I levels within normal range for age is due to endogenous basal GH production being sufficient or other factors stimulating IGF-I, IGFBP-3 or ALS expressions.