Biochemical markers of individual response to growth hormone replacement in adults

Options for determining the response to growth hormone (GH) replacement in adults include symptomatic response, changes in body composition and measurement of biochemical markers of GH action. It has become apparent from various studies and during routine clinical practice that abnormal elevation of serum markers of GH action during GH therapy may not be associated with either adverse symptoms or abnormalities in body composition, thereby limiting the value of subjective assessment and physical characteristics as safety markers of over-treatment. Candidate biochemical markers include insulin-like growth factor I (IGF-I), IGF-binding protein 3 (IGFBP-3) and the acid-labile subunit (ALS), and markers of bone remodelling. No single measurement provides an ideal index of adequacy of GH replacement. Serum IGF-I has the greatest utility during GH dose titration as it is more sensitive to changes in GH status than IGFBP-3 and ALS, and is also more sensitive to excessive GH replacement. IGF-I, therefore, provides an important safety marker. Furthermore, changes in IGF-I correlate with improvements in body composition. Changes in circulating insulin and leptin occur during GH therapy, but are significantly influenced by changes in body fat and its distribution and do not provide useful information upon which to gauge responsiveness to GH. Markers of bone remodelling are an important indicator of GH action within individuals, but exhibit wide inter-individual variation which limits their usefulness in defining relative GH responsiveness.