Normal values of circulating insulin-like growth factor-I bioactivity in the healthy population: comparison with five widely used IGF-I immunoassays.
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.


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


METHODS
Participants included 426 healthy individuals (310 males, 116 females; age range 18-79 yr).


METHODS
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 (beta = -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.
Brugts
Michael P
MP
Department of Internal Medicine, Erasmus MC, Dr. Molewaterplein 50, Rotterdam, The Netherlands. m.brugts@erasmusmc.nl
Ranke
Michael B
MB
Hofland
Leo J
LJ
van der Wansem
Katy
K
Weber
Karin
K
Frystyk
Jan
J
Lamberts
Steven W J
SW
Janssen
Joseph A M J L
JA
D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007118:Immunoassay; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D012016:Reference Values
D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1