IGF-I Bioactivity Better Reflects Growth Hormone Deficiency than Total IGF-I

Context: GH is considered the main regulator of circulating IGF-I. Total (extractable) IGF-I is therefore routinely used for diagnosis of GH deficiency (GHD) and for monitoring treatment. Methods currently used for measurement of circulating total IGF-I may be hampered by interferences of IGF-binding proteins. Recently a kinase receptor activation assay was developed to determine IGF-I bioactivity in human serum. The principle of this assay is based on quantification of IGF-I receptor activation after stimulation with serum in vitro. Objective: The objective of the study was to investigate the diagnostic potential of IGF-I bioactivity in adults with GHD. Design: This was a single-center observational study. Study Participants: Ninety-four GH-untreated patients diagnosed with GHD by GH-provocative tests were included. Main Outcome Measures: IGF-I bioactivity (determined by the IGF-I kinase receptor activation assay) and total IGF-I (determined by immunoassay) were measured in fasting blood samples. Results: IGF-I bioactivity was more frequently below the normal range (<- 2 SD) in untreated GH-deficient patients than total IGF-I levels (81.9 vs. 61.7%, respectively), especially in patients older than 40 years of age. IGF-I bioactivity decreased with the duration of GHD, whereas total IGF-I did not. With a decreasing number of additional pituitary deficits, total IGF-I levels more frequently remained within the normal range, whereas the percentage below the normal range was high for IGF-I bioactivity, independent of additional deficits. Conclusion: Determination of IGF-I bioactivity may offer advantages in the evaluation of adult GHD compared with total IGF-I as bioactivity better reflects GHD as defined by GH stimulation tests, especially in subjects older than 40 years of age. (J Clin Endocrinol Metab 96: 2248-2254, 2011)