Journal of Clinical Endocrinology & Metabolism, Vol 78, 744-752, Copyright © 1994 by Endocrine Society

ARTICLES

Serum insulin-like growth factor-I in 1030 healthy children, adolescents, and adults: relation to age, sex, stage of puberty, testicular size, and body mass index

A Juul, P Bang, NT Hertel, K Main, P Dalgaard, K Jorgensen, J Muller, K Hall and NE Skakkebaek
Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark.

Serum levels of insulin-like growth factor-I (IGF-I) increase with age and pubertal development. The large variation in circulating IGF-I levels in adolescence makes it difficult to use the IGF-I value of a single child in the assessment of his growth status. In addition, the interference of IGF-binding proteins in many IGF-I assays contributes to this problem. We measured IGF-I in acid-ethanol-extracted serum from 1030 healthy children, adolescents, and adults, employing a RIA that reduces interference of IGF-binding proteins by using monoiodinated Tyr31-[125I]des-(1-3)IGF-I as radioligand. Mean serum IGF-I concentrations increased slowly in prepubertal children from 80-200 micrograms/L with a further steep increase during puberty to approximately 500 micrograms/L. After puberty, a subsequent continuous fall in circulating IGF-I levels was apparent throughout adulthood to a mean of 100 micrograms/L at the age of 80 yr (P < 0.0001). Girls had maximal IGF-I levels at 14.5 yr of age, whereas boys had peak IGF-I levels 1 yr later. This is almost 2 yr later than average peak height velocity. The large variation in serum IGF-I levels during puberty was diminished when data were separated according to sex and Tanner stage of puberty. Interestingly, we found a significant variation with age within the Tanner stages; there was an increase in serum IGF-I concentrations with age in the early pubertal stages and a decrease in the late stages (P < 0.05). Serum IGF-I increased concomitantly with increasing testicular volume. Multiple regression analysis revealed that serum IGF-I levels predicted height velocity in the following year (r = 0.33; P < 0.0001). Body mass index did not correlate significantly with serum IGF-I in prepubertal children in a multiple regression analysis. In conclusion, there was a significant variation in serum IGF- I levels with age within a given Tanner stage of puberty in addition to the well known increase with increasing age or pubertal stage. Accordingly, the effects of sex, age, and puberty on serum IGF-I cannot be separated into simple additive components when studying 1030 children in a cross-sectional design. Thus, the age-, sex-, and puberty- corrected IGF-I values may, in fact, improve the use of serum IGF-I as a diagnostic tool to distinguish between a child with retarded puberty and a GH-deficient individual.

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				R. Dall, S. Longobardi, C. Ehrnborg, N. Keay, T. Rosén, J. O. L. Jørgensen, R. C. Cuneo, M. A. Boroujerdi, A. Cittadini, R. Napoli, et al. The Effect of Four Weeks of Supraphysiological Growth Hormone Administration on the Insulin-Like Growth Factor Axis in Women and Men J. Clin. Endocrinol. Metab., November 1, 2000; 85(11): 4193 - 4200. [Abstract] [Full Text]

				K. H. W. Lange, F. Isaksson, A. Juul, M. H. Rasmussen, J. Bulow, and M. Kjar Growth hormone enhances effects of endurance training on oxidative muscle metabolism in elderly women Am J Physiol Endocrinol Metab, November 1, 2000; 279(5): E989 - E996. [Abstract] [Full Text] [PDF]

				G. D. Smith, D. Gunnell, and J. Holly Cancer and insulin-like growth factor-I BMJ, October 7, 2000; 321(7265): 847 - 848. [Full Text]

				H. Yu and T. Rohan Role of the Insulin-Like Growth Factor Family in Cancer Development and Progression J Natl Cancer Inst, September 20, 2000; 92(18): 1472 - 1489. [Abstract] [Full Text] [PDF]

				O. Akre, A. Ekbom, P. Sparen, and S. Tretli Body Size and Testicular Cancer J Natl Cancer Inst, July 5, 2000; 92(13): 1093 - 1096. [Full Text] [PDF]

				E. Giovannucci, M. N. Pollak, E. A. Platz, W. C. Willett, M. J. Stampfer, N. Majeed, G. A. Colditz, F. E. Speizer, and S. E. Hankinson A Prospective Study of Plasma Insulin-like Growth Factor-1 and Binding Protein-3 and Risk of Colorectal Neoplasia in Women Cancer Epidemiol. Biomarkers Prev., April 1, 2000; 9(4): 345 - 349. [Abstract] [Full Text]

				A. Sehested, A. Juul, A. M. Andersson, J. H. Petersen, T. K. Jensen, J. Müller, and N. E. Skakkebaek Serum Inhibin A and Inhibin B in Healthy Prepubertal, Pubertal, and Adolescent Girls and Adult Women: Relation to Age, Stage of Puberty, Menstrual Cycle, Follicle-Stimulating Hormone, Luteinizing Hormone, and Estradiol Levels J. Clin. Endocrinol. Metab., April 1, 2000; 85(4): 1634 - 1640. [Abstract] [Full Text]

				W. L. Dees, G. A. Dissen, J. K. Hiney, F. Lara, and S. R. Ojeda Alcohol Ingestion Inhibits the Increased Secretion of Puberty-Related Hormones in the Developing Female Rhesus Monkey Endocrinology, April 1, 2000; 141(4): 1325 - 1331. [Abstract] [Full Text] [PDF]

				G. D. Smith, C. Hart, M. Upton, D. Hole, C. Gillis, G. Watt, and V. Hawthorne Height and risk of death among men and women: aetiological implications of associations with cardiorespiratory disease and cancer mortality J Epidemiol Community Health, February 1, 2000; 54(2): 97 - 103. [Abstract] [Full Text]

				E. Eugster Gigantism J. Clin. Endocrinol. Metab., December 1, 1999; 84(12): 4379 - 4384. [Full Text]

				M. H. Aguiar-Oliveira, M. S. Gill, E. S. de, A. Barretto, M. R. S. Alcântara, F. Miraki-Moud, C. A. Menezes, A. H. O. Souza, C. E. Martinelli, F. A. Pereira, et al. Effect of Severe Growth Hormone (GH) Deficiency due to a Mutation in the GH-Releasing Hormone Receptor on Insulin-Like Growth Factors (IGFs), IGF-Binding Proteins, and Ternary Complex Formation Throughout Life J. Clin. Endocrinol. Metab., November 1, 1999; 84(11): 4118 - 4126. [Abstract] [Full Text]

				L. Hansen, J. Bangsbo, J. Twisk, and K. Klausen Development of muscle strength in relation to training level and testosterone in young male soccer players J Appl Physiol, September 1, 1999; 87(3): 1141 - 1147. [Abstract] [Full Text] [PDF]

				D. Deplewski and R. L. Rosenfield Growth Hormone and Insulin-Like Growth Factors Have Different Effects on Sebaceous Cell Growth and Differentiation Endocrinology, September 1, 1999; 140(9): 4089 - 4094. [Abstract] [Full Text]

				S. Mora, P. Pitukcheewanont, J. C. Nelson, and V. Gilsanz Serum Levels of Insulin-Like Growth Factor I and the Density, Volume, and Cross-Sectional Area of Cortical Bone in Children J. Clin. Endocrinol. Metab., August 1, 1999; 84(8): 2780 - 2783. [Abstract] [Full Text]

				A. Bitar, N. Fellmann, J. Vernet, J. Coudert, and M. Vermorel Variations and determinants of energy expenditure as measured by whole-body indirect calorimetry during puberty and adolescence Am. J. Clinical Nutrition, June 1, 1999; 69(6): 1209 - 1216. [Abstract] [Full Text] [PDF]

				A. M Lund, J. Müller, and F. Skovby Anthropometry of patients with osteogenesis imperfecta Arch. Dis. Child., June 1, 1999; 80(6): 524 - 528. [Abstract] [Full Text]

				K. D. Burroughs, S. E. Dunn, J. C. Barrett, and J. A. Taylor Insulin-Like Growth Factor-I: a Key Regulator of Human Cancer Risk? J Natl Cancer Inst, April 7, 1999; 91(7): 579 - 581. [Full Text] [PDF]

				J. Ma, M. N. Pollak, E. Giovannucci, J. M. Chan, Y. Tao, C. H. Hennekens, and M. J. Stampfer Prospective Study of Colorectal Cancer Risk in Men and Plasma Levels of Insulin-Like Growth Factor (IGF)-I and IGF-Binding Protein-3 J Natl Cancer Inst, April 7, 1999; 91(7): 620 - 625. [Abstract] [Full Text] [PDF]

				G Annerén, T Tuvemo, C Carlsson-Skwirut, T Lönnerholm, P Bang, V R Sara, and J Gustafsson Growth hormone treatment in young children with Down's syndrome: effects on growth and psychomotor development Arch. Dis. Child., April 1, 1999; 80(4): 334 - 338. [Abstract] [Full Text]

				H. Yu, M. R. Spitz, J. Mistry, J. Gu, W. K. Hong, and X. Wu Plasma Levels of Insulin-Like Growth Factor-I and Lung Cancer Risk: a Case-Control Analysis J Natl Cancer Inst, January 20, 1999; 91(2): 151 - 156. [Abstract] [Full Text] [PDF]

				N. Kawai, S. Kanzaki, S. Takano-Watou, C. Tada, Y. Yamanaka, T. Miyata, M. Oka, and Y. Seino Serum Free Insulin-Like Growth Factor I (IGF-I), Total IGF-I, and IGF-Binding Protein-3 Concentrations in Normal Children and Children with Growth Hormone Deficiency J. Clin. Endocrinol. Metab., January 1, 1999; 84(1): 82 - 89. [Abstract] [Full Text]

				A. Juul, S. Møller, E. Mosfeldt-Laursen, M. H. Rasmussen, T. Scheike, S. A. Pedersen, K. W. Kastrup, H. Yu, J. Mistry, S. Rasmussen, et al. The Acid-Labile Subunit of Human Ternary Insulin-Like Growth Factor Binding Protein Complex in Serum: Hepatosplanchnic Release, Diurnal Variation, Circulating Concentrations in Healthy Subjects, and Diagnostic Use in Patients with Growth Hormone Deficiency J. Clin. Endocrinol. Metab., December 1, 1998; 83(12): 4408 - 4415. [Abstract] [Full Text]

				S. L. S. Drop, W. J. de Waal, and S. M. P. F. de Muinck Keizer-Schrama Sex Steroid Treatment of Constitutionally Tall Stature Endocr. Rev., October 1, 1998; 19(5): 540 - 558. [Abstract] [Full Text]

				J. Frystyk, H. Gronbak, C. Skjarbak, A. Flyvbjerg, H. Orskov, and R. C. Baxter Developmental Changes in Serum Levels of Free and Total Insulin-Like Growth Factor I (IGF-I), IGF-Binding Protein-1 and -3, and the Acid-Labile Subunit in Rats Endocrinology, October 1, 1998; 139(10): 4286 - 4292. [Abstract] [Full Text] [PDF]

				B. E. Engstrom, F. A. Karlsson, and L. Wide Marked gender differences in ambulatory morning growth hormone values in young adults Clin. Chem., June 1, 1998; 44(6): 1289 - 1295. [Abstract] [Full Text] [PDF]

				M. Christopher, F. L. Hew, M. Oakley, C. Rantzau, and F. Alford Defects of Insulin Action and Skeletal Muscle Glucose Metabolism in Growth Hormone-Deficient Adults Persist after 24 Months of Recombinant Human Growth Hormone Therapy J. Clin. Endocrinol. Metab., May 1, 1998; 83(5): 1668 - 1681. [Abstract] [Full Text]

				S. M. Shalet, A. Toogood, A. Rahim, and B. M. D. Brennan The Diagnosis of Growth Hormone Deficiency in Children and Adults Endocr. Rev., April 1, 1998; 19(2): 203 - 223. [Abstract] [Full Text]