Plasma levels of insulin-like binding protein-2 in prepubertal short children and its diagnostic value in the evaluation of growth hormone deficiency.
OBJECTIVE
This study was designed to investigate whether determination of plasma insulin-like growth factor (IGF)-binding protein-2 (IGFBP-2) levels could be of benefit in the evaluation of childhood growth hormone (GH) deficiency (GHD).


METHODS
A retrospective analysis was performed on 91 prepubertal children referred for investigation of short stature. Maximal GH levels in plasma after provocative stimuli were between 1.0 and 93.0 mU/l, 6 subjects exhibiting peak values of <5 mU/l. Initially a GH peak of 20 mU/l was used as a cutoff limit to define GHD and idiopathic short stature (ISS) patients. The results of GH provocative tests were compared to age- and gender-based standard deviation scores (SDS) of plasma IGFBP-2, IGF-I, IGFBP-3 and the molar ratios of the latter two to IGFBP-2. The respective normative range values for these parameters were determined in plasma samples from 353 healthy children (i.e. 171 girls, 182 boys).


RESULTS
Circulating IGFBP-2 levels did not correlate with height SDS, height velocity SDS or the peak GH levels after provocative stimuli. A weak negative relationship was found between IGFBP-2 and IGF-I. Plasma levels of IGFBP-2 in GHD patients were higher than those of ISS children, who had normal levels. Although at the optimal cutoff point of -0.71 SDS 91.5% of the GHD patients were identified correctly, a substantial proportion (71.9%) of the ISS subjects also had IGFBP-2 levels above this limit. The use of various combinations of IGFBP-2, IGF-I, IGFBP-3 and the derived ratios only slightly improved the diagnostic efficiency as compared to the results of the individual tests. Neither IGFBP-2 nor the IGFBP-3/IGFBP-2 and IGF-I/IGFBP-2 ratios were found to be related to the short- (1 year) or long-term (3 years) growth response to GH therapy.


CONCLUSIONS
It is concluded that none of the tests investigated, either alone or in various combinations, are reliable in either predicting the peak GH level after provocative stimuli in prepubertal short children or in predicting their growth response to GH.
van Doorn
J
J
Department of Pediatrics, Laboratory of Endocrinology, Wilhelmina Children's Hospital/University Medical Center Utrecht, NL-3508 AB Utrecht, The Netherlands. J.vanDoorn@lab.azu.nl
Ringeling
A M
AM
Rikken
B
B
van Buul-Offers
S C
SC
D000293:Adolescent; D001827:Body Height; D002648:Child; D002675:Child, Preschool; D005260:Female; D006130:Growth Disorders / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy; D013006:Growth Hormone / Q000172:deficiency*; D019382:Human Growth Hormone / Q000627:therapeutic use; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D011237:Predictive Value of Tests; D011627:Puberty / Q000097:blood; D012189:Retrospective Studies
D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone