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Normal Values of Circulating Insulin-Like Growth Factor-I Bioactivity in the Healthy Population: Comparison with Five Widely Used IGF-I Immunoassays

Division of Endocrinology (M.P.B., L.J.H., K.v.d.W., S.W.J.L., J.A.M.J.L.J.), Department of Internal Medicine, Erasmus Medical Center, 3015 GE Rotterdam, The Netherlands; Pediatric Endocrinology Section (M.B.R., K.W.), University Children’s Hospital, D-72074 Tuebingen, Germany; and Medical Research Laboratories (J.F.), Clinical Institute and Medical Department M, Aarhus University Hospital, DK-8000 Aarhus C, Denmark

Address all correspondence and requests for reprints to: Michael Pascal Brugts, Department of Internal Medicine, Erasmus MC, Room Ee569, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands, E-mail: m.brugts{at}erasmusmc.nl.

Background: IGF-I immunoassays are primarily used to estimate IGF-I bioactivity. Recently an IGF-I-specific kinase receptor activation assay (KIRA) has been developed as an alternative method. However, no normative values have been established for the IGF-I KIRA.

Objective: The objective of the study was to establish normative values for the IGF-I KIRA in healthy adults.

Design: This was a cross-sectional study in healthy nonfasting blood donors.

Study Participants: Participants included 426 healthy individuals (310 males, 116 females; age range 18–79 yr).

Main Outcome Measures: IGF-I bioactivity determined by the KIRA was measured. Results were compared with total IGF-I, measured by five different IGF-I immunoassays.

Results: Mean (± SD) IGF-I bioactivity was 423 (± 131) pmol/liter and decreased with age (β = –3.4 pmol/liter·yr, P < 0.001). In subjects younger than 55 yr, mean IGF-I bioactivity was significantly higher in women than men. Above this age this relationship was inverse, suggesting a drop in IGF-I bioactivity after menopause. This drop was not reflected in total IGF-I levels. IGF-I bioactivity was significantly related to total IGF-I (r_s varied between 0.46 and 0.52; P < 0.001).

Conclusions: We established age-specific normative values for the IGF-I KIRA. We observed a significant drop in IGF-I bioactivity in women between 50 and 60 yr, which was not perceived by IGF-I immunoassays. The IGF-I KIRA, when compared with IGF-I immunoassays, theoretically has the advantage that it measures net effects of IGF-binding proteins on IGF-I receptor activation. However, it has to be proven whether information obtained by the IGF-I KIRA is clinically more relevant than measurements obtained by IGF-I immunoassays.