Journal of Clinical Endocrinology & Metabolism, Vol 81, 3902-3908, Copyright © 1996 by Endocrine Society

ARTICLES

Changes in serum insulin-like growth factor I (IGF-I) and IGF-binding protein-3 levels during growth hormone treatment in prepubertal short children born small for gestational age

M Boguszewski, C Jansson, S Rosberg and K Albertsson-Wikland
Department of Pediatrics, University of Goteborg, Sweden.

The aims of this study were to describe the basal serum levels of insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP- 3) and to evaluate their changes during daily GH treatment (0.1 IU/kg; 33 micrograms/kg) for up to 2 yr in prepubertal short children born small for gestational age (SGA) and to correlate these changes with the growth response to GH therapy. Seventy-two prepubertal short children (height SD score, -5.4 to -2.0; age, 2.0-12.9 yr) born SGA (54 boys and 18 girls), eight of whom (six boys and two girls) had signs of Silver- Russell syndrome, participated in the study. The serum concentrations of IGF-I and IGFBP-3 were converted into SDS using our reference values for prepubertal healthy children. The mean (+/-SD) change in height SDS during the year before the start of GH treatment was 0.1 (0.2) and increased to 0.8 (0.4) during the first year (P < 0.001) and to 0.6 (0.3) during the second year of therapy (P < 0.001). Basal levels of both IGF-I and IGFBP-3 were significantly reduced compared with the reference values. The mean (+/-SD) basal serum concentration of IGF-I was -0.6 (1.1) SD score, and 80% of the SGA children had IGF-I levels below the 50th percentile of the reference group. The corresponding values for IGFBP-3 were -0.4 (1.0) SD score and 63%. The mean IGF-I level increased significantly by 55% from baseline to day 10 of treatment, by 76% on day 90, by 90% after 1 yr, and by 123% after 2 yr of GH treatment. The mean increases in IGFBP-3 were not as great: 25%, 27%, 35%, and 43%, respectively. The 1-yr growth response, expressed as the change in height SD score, correlated negatively with both the basal serum concentration of IGF-I (r = -0.37; P < 0.001) and IGFBP-3 (r = -0.35; P < 0.01), whereas a positive correlation was found to the 10-day percent increase in IGF-I (r = 0.32; P < 0.05). No correlations were found with the initial changes in IGFBP-3. Using a multiple stepwise linear regression analysis, the model using chronological age at the start of GH therapy, the mother's height expressed as a SD score, and the short term percent increase in IGF-I accounted for 42% of the variance in the 1-yr growth response. With the inclusion of 24-h GH profiles, 59% of the variability of the growth response could be explained. It is concluded that short prepubertal children born SGA show an increased growth rate in response to GH therapy. Their mean IGF- I and IGFBP-3 levels before treatment were low and correlated negatively with the growth response to treatment, indicating GH insufficiency. Finally, up to 59% of the variability in the 1-yr growth response to GH treatment could be explained by models using auxological and biochemical variables.

This article has been cited by other articles:

				L. Audi, A. Carrascosa, C. Esteban, M. Fernandez-Cancio, P. Andaluz, D. Yeste, R. Espadero, M. L. Granada, H. Wollmann, L. Fryklund, et al. The exon 3-deleted/full-length Growth Hormone Receptor Polymorphism Does Not Influence the Effect of Puberty or Growth Hormone Therapy on Glucose Homeostasis in Short Non-Growth Hormone-Deficient Small-for-Gestational-Age Children: Results from a Two-Year Controlled Prospective Study J. Clin. Endocrinol. Metab., July 1, 2008; 93(7): 2709 - 2715. [Abstract] [Full Text] [PDF]

				G. Binder, A.-K. Seidel, D. D. Martin, R. Schweizer, C. P. Schwarze, H. A. Wollmann, T. Eggermann, and M. B. Ranke The Endocrine Phenotype in Silver-Russell Syndrome Is Defined by the Underlying Epigenetic Alteration J. Clin. Endocrinol. Metab., April 1, 2008; 93(4): 1402 - 1407. [Abstract] [Full Text] [PDF]

				C. Lotton, D. Rodrigue, C. Elie, A. Rothenbuhler, N. Lahlou, C. Le Stunff, and P. Bougneres Akt Phosphorylation in Lymphocytes Provides an Index of in Vitro Insulin-Like Growth Factor I Sensitivity Associated with Growth Hormone-Induced Growth J. Clin. Endocrinol. Metab., April 1, 2008; 93(4): 1458 - 1463. [Abstract] [Full Text] [PDF]

				E. M. N. Bannink, J. van Doorn, P. G. H. Mulder, and A. C. S. Hokken-Koelega Free/Dissociable Insulin-Like Growth Factor (IGF)-I, Not Total IGF-I, Correlates with Growth Response during Growth Hormone Treatment in Children Born Small for Gestational Age J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 2992 - 3000. [Abstract] [Full Text] [PDF]

				J. Argente, R. Gracia, L. Ibanez, A. Oliver, E. Borrajo, A. Vela, J. P. Lopez-Siguero, M. L. Moreno, F. Rodriguez-Hierro, and on behalf of the Spanish SGA Working Group Improvement in Growth after Two Years of Growth Hormone Therapy in Very Young Children Born Small for Gestational Age and without Spontaneous Catch-Up Growth: Results of a Multicenter, Controlled, Randomized, Open Clinical Trial J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 3095 - 3101. [Abstract] [Full Text] [PDF]

				P. Cohen, A. D. Rogol, C. P. Howard, G. M. Bright, A.-M. Kappelgaard, R. G. Rosenfeld, and on behalf of the American Norditropin Study Group Insulin Growth Factor-Based Dosing of Growth Hormone Therapy in Children: A Randomized, Controlled Study J. Clin. Endocrinol. Metab., July 1, 2007; 92(7): 2480 - 2486. [Abstract] [Full Text] [PDF]

				P. Saenger, P. Czernichow, I. Hughes, and E. O. Reiter Small for Gestational Age: Short Stature and Beyond Endocr. Rev., April 1, 2007; 28(2): 219 - 251. [Abstract] [Full Text] [PDF]

				M. van Dijk, E. M. N. Bannink, Y. K. van Pareren, P. G. H. Mulder, and A. C. S. Hokken-Koelega Risk Factors for Diabetes Mellitus Type 2 and Metabolic Syndrome Are Comparable for Previously Growth Hormone-Treated Young Adults Born Small for Gestational Age (SGA) and Untreated Short SGA Controls J. Clin. Endocrinol. Metab., January 1, 2007; 92(1): 160 - 165. [Abstract] [Full Text] [PDF]

				M. van Dijk, P. Mulder, M. Houdijk, J. Mulder, K. Noordam, R. J. Odink, C. Rongen-Westerlaken, P. Voorhoeve, J. Waelkens, J. Stokvis-Brantsma, et al. High Serum Levels of Growth Hormone (GH) and Insulin-Like Growth Factor-I (IGF-I) during High-Dose GH Treatment in Short Children Born Small for Gestational Age J. Clin. Endocrinol. Metab., April 1, 2006; 91(4): 1390 - 1396. [Abstract] [Full Text] [PDF]

				R. Verkauskiene, D. Jaquet, S. Deghmoun, D. Chevenne, P. Czernichow, and C. Levy-Marchal Smallness for Gestational Age Is Associated with Persistent Change in Insulin-Like Growth Factor I (IGF-I) and the Ratio of IGF-I/IGF-Binding Protein-3 in Adulthood J. Clin. Endocrinol. Metab., October 1, 2005; 90(10): 5672 - 5676. [Abstract] [Full Text] [PDF]

				Y. K. van Pareren, H. J. Duivenvoorden, F. S. M. Slijper, H. M. Koot, and A. C. S. Hokken-Koelega Intelligence and Psychosocial Functioning during Long-Term Growth Hormone Therapy in Children Born Small for Gestational Age J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5295 - 5302. [Abstract] [Full Text] [PDF]

				R. Bjarnason, B. Andersson, H. S. Kim, B. Olsson, D. Swolin-Eide, R. Wickelgren, B. Kristrom, B. Carlsson, K. Albertsson-Wikland, L. M. S. Carlsson, et al. Cartilage Oligomeric Matrix Protein Increases in Serum after the Start of Growth Hormone Treatment in Prepubertal Children J. Clin. Endocrinol. Metab., October 1, 2004; 89(10): 5156 - 5160. [Abstract] [Full Text] [PDF]

				L B Johnston and M O Savage Should recombinant human growth hormone therapy be used in short small for gestational age children? Arch. Dis. Child., August 1, 2004; 89(8): 740 - 744. [Abstract] [Full Text] [PDF]

				A. Fjellestad-Paulsen, D. Simon, and P. Czernichow Short Children Born Small for Gestational Age and Treated with Growth Hormone for Three Years Have an Important Catch-Down Five Years after Discontinuation of Treatment J. Clin. Endocrinol. Metab., March 1, 2004; 89(3): 1234 - 1239. [Abstract] [Full Text] [PDF]

				P. A. Lee, J. W. Kendig, and J. R. Kerrigan Persistent Short Stature, Other Potential Outcomes, and the Effect of Growth Hormone Treatment in Children Who Are Born Small for Gestational Age Pediatrics, July 1, 2003; 112(1): 150 - 162. [Full Text] [PDF]

				W. S. Cutfield, P. L. Hofman, M. Vickers, B. Breier, W. F. Blum, and E. M. Robinson IGFs and Binding Proteins in Short Children with Intrauterine Growth Retardation J. Clin. Endocrinol. Metab., January 1, 2002; 87(1): 235 - 239. [Abstract] [Full Text] [PDF]

				T. Sas, P. Mulder, and A. Hokken-Koelega Body Composition, Blood Pressure, and Lipid Metabolism before and during Long-Term Growth Hormone (GH) Treatment in Children with Short Stature Born Small for Gestational Age Either with or without GH Deficiency J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3786 - 3792. [Abstract] [Full Text]

				T. Sas, W. de Waal, P. Mulder, M. Houdijk, M. Jansen, M. Reeser, and A. Hokken-Koelega Growth Hormone Treatment in Children with Short Stature Born Small for Gestational Age: 5-Year Results of a Randomized, Double-Blind, Dose-Response Trial J. Clin. Endocrinol. Metab., September 1, 1999; 84(9): 3064 - 3070. [Abstract] [Full Text]

				A. Hellström, E. Svensson, B. Carlsson, A. Niklasson, and K. Albertsson-Wikland Reduced Retinal Vascularization in Children with Growth Hormone Deficiency J. Clin. Endocrinol. Metab., February 1, 1999; 84(2): 795 - 798. [Abstract] [Full Text]

				B. Kriström, B. Carlsson, S. Rosberg, L. M. S. Carlsson, and K. Albertsson-Wikland Short-Term Changes in Serum Leptin Levels Provide a Strong Metabolic Marker for the Growth Response to Growth Hormone Treatment in Children J. Clin. Endocrinol. Metab., August 1, 1998; 83(8): 2735 - 2741. [Abstract] [Full Text]

				J. C. Achermann, K. Hamdani, P. C. Hindmarsh, and C. G. D. Brook Birth Weight Influences the Initial Response to Growth Hormone Treatment in Growth Hormone-insufficient Children Pediatrics, August 1, 1998; 102(2): 342 - 345. [Abstract] [Full Text] [PDF]

				C. L. Boguszewski, C. Jansson, M. C. S. Boguszewski, S. Rosberg, B. Carlsson, K. Albertsson-Wikland, and L. M. S. Carlsson Increased Proportion of Circulating Non-22-Kilodalton Growth Hormone Isoforms in Short Children: A Possible Mechanism for Growth Failure J. Clin. Endocrinol. Metab., September 1, 1997; 82(9): 2944 - 2949. [Abstract] [Full Text] [PDF]

				F. d. Zegher, I. Francois, m. van helvoirt, and g. van den berghe Small as Fetus and Short as Child: From Endogenous to Exogenous Growth Hormone J. Clin. Endocrinol. Metab., July 1, 1997; 82(7): 2021 - 2026. [Full Text] [PDF]

				M. Boguszewski, R. Bjarnason, S. Rosberg, L. M. S. Carlsson, and K. Albertsson-Wikland Growth Hormone (GH)-Binding Protein in Prepubertal Short Children Born Small for Gestational Age: Effects of Growth Hormone Treatment J. Clin. Endocrinol. Metab., April 1, 1997; 82(4): 1014 - 1019. [Abstract] [Full Text] [PDF]