Failure of IGF-I and IGFBP-3 to diagnose growth hormone insufficiency.
BACKGROUND
Growth hormone insufficiency (GHI) is diagnosed conventionally by short stature and slow growth, and is confirmed by diminished peak GH response to a provocation test. Insulin-like growth factor I (IGF-I) and IGF binding protein 3 (IGFBP-3) have previously been considered individually


OBJECTIVE
To test the hypothesis that the combined analysis of IGF-I and IGFBP-3 could act as a surrogate marker for the diagnosis of GHI.


METHODS
Reference ranges for IGF-I and IGFBP-3 were calculated using 521 normal individuals. A retrospective analysis was performed on 318 children referred for investigation of short stature.


RESULTS
No significant difference was found between either the IGF-I or IGFBP-3 standard deviation scores (SDSs) in children with and without GHI. If the requirement were for both tests to be positive (< -2 SDS) for a diagnosis of GHI, then 99% of children without GHI would be correctly identified; however, the sensitivity of the test was only 15%.


CONCLUSIONS
Neither IGF-I nor IGFBP-3 alone is a marker for GHI. In addition, they cannot be used as an effective screening test in combination.
Mitchell
H
H
London Centre for Paediatric Endocrinology, Great Ormond Street and The Middlesex Hospitals, London W1H 8AA, UK.
Dattani
M T
MT
Nanduri
V
V
Hindmarsh
P C
PC
Preece
M A
MA
Brook
C G
CG
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001827:Body Height; D002648:Child; D002675:Child, Preschool; D005260:Female; D006130:Growth Disorders / Q000175:diagnosis*; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D007223:Infant; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
D015415:Biomarkers; D018972:Insulin-Like Growth Factor Binding Protein 3; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I