Background: Little information is available on the relevance of parameters representing the insulin-like growth factor (IGF) system with regard to growth hormone (GH) treatment during childhood. In adults, high IGF-I levels were found to be associated with side effects and long-term risks. Aim/Method: Our aim was to monitor the serum levels of IGF-I, IGF-binding protein (IGFBP) 3, and IGFBP-2 during long-term GH treatment of 156 patients with GH deficiency (GHD) and of 153 non-GHD patients. We determined the extent to which the IGF parameters exceed the normal ranges and identified those parameters which are predictive of 1st-year growth. Results: In prepubertal GHD children, the levels of IGF-I, IGFBP-3, and IGF-I/IGFBP-3 exceeded the 95th centile of the reference values for this age group in 2.3, 0.3, and 7.9% of the cases, respectively, whereas in prepubertal non-GHD children, the same parameters exceeded the 95th reference centile in 20.1, 3.5, and 32.2%, respectively. In pubertal GHD children IGF-I, IGFBP-3, and IGF-I/IGFBP-3 levels exceeded the 95th reference centile in 11.1, 1.5, and 15.4%, respectively. In pubertal non-GHD children, these levels also exceeded the 95th centile in 26.7, 7.0, and 41.4%, respectively. In both GHD and non-GHD groups, however, some patients had IGF parameters which were below the reference values. Our analysis showed that, in both groups, in addition to maximum GH, all IGF parameters (IGF-I, IGFBP-3, IGF-I/IGFBP-3 ratio, IGFBP-2 or derivatives) significantly extend the scope of a calculated model for predicting 1st-year height velocity. Conclusion: For reasons of safety and optimization of GH therapy, it is essential to follow up IGF-I, IGFBP-3, and IGFBP-2 levels regularly during childhood.

1.
Ranke MB, Lindberg A, Chatelain P, Wilton P, Cutfield W, Albertsson-Wikland KA, Price DA: Derivation and validation of a mathematical model for predicting the response to exogenous recombinant human growth hormone (GH) in prepubertal children with idiopathic GH deficiency. J Clin Endocrinol Metab 1999;84:1174–1183.
2.
Clayton PE: The role of insulin-like growth factors in the diagnosis of growth hormone deficiency; in Ranke MB, Wilton P (eds): Growth Hormone Therapy in KIGS: 10 Years’ Experience. Heidelberg, Johann Ambrosius Barth Verlag, 1999, pp 53–64.
3.
Rasat R, Livesey JL, Espiner EA, Abbott GD, Donald RA: IGF-1 and IGFBP-3 screening for disorders of growth hormone secretion. NZ Med J 1996;109:156–159.
4.
Ranke MB, Schweizer R, Elmlinger MW, Weber K, Binder G, Schwarze CP, Wollmann HA: Significance of basal IGF-I, IGFBP-3 and IGFBP-2 measurements in the diagnostics of short stature in children. Horm Res 2000;54:60–68.
5.
Prader A, Largo RH, Molinari L, Issler C: Physical growth of Swiss children from birth to 20 years of age: First Zürich longitudinal study of growth and development. Helv Paediatr Acta Suppl 1989;52:1–125.
6.
Niklasson A, Ericson A, Fryer JG, Karlberg J, Lawrence C, Karlberg P: An update in the Swedish reference standards for weight, length and head circumference at birth for given gestational age (1977–1981). Acta Paediatr Scand 1991;80:756–762.
7.
Tanner JM: A correction to the TW2 RUS-based tables for predicting adult height. Ann Hum Biol 1978;5:491–492.
8.
Blum WF, Breier BH: Radioimmunoassays for IGFs and IGFBPs. Growth Regul 1994;1 (suppl 1):11–19.
9.
Blum WF, Ranke MB, Kietzmann K, Gauggel E, Zeisel HJ, Bierich JR: A specific radioimmunoassay for the growth hormone (GH)-dependent somatomedin-binding protein: Its use for diagnosis of GH deficiency. J Clin Endocrinol Metab 1990;70:1292–1298.
10.
Elmlinger MW, Wimmer K, Biemer E, Blum WF, Ranke MB, Dannecker GE: Insulin-like growth factor binding protein 2 is differentially expressed in leukaemic B- and T-cell lines. Growth Regul 1996;6:152–157.
11.
Mayer EIE, Ranke MB: Non-compliance with growth hormone treatment. Monatsschr Kinderheilk 1997;145:502–505.
12.
Drake WM, Coyte D, Camacho-Hubner C, Jivanji NM, Kaltsas G, Wood DF, Trainer PJ, Grossman AB, Besser GM, Monson JP: Optimizing growth hormone replacement therapy by dose titration in hypopituitary adults. J Clin Endocrinol Metab 1998;83:3913–3919.
13.
de Boer H, Blok GJ, Popp SC, Snijders C, Stuurman L, Baxter RC, van der Veen: Monitoring of growth hormone replacement therapy in adults, based on measurement of serum markers. J Clin Endocrinol Metab 1996;81:1371–1377.
14.
Mardh G, Lundin K, Borg G, Jonsson B, Lindeberg A: Growth hormone replacement therapy in adult hypopituitary patients with growth hormone deficiency: Combined data from 12 European placebo-controlled clinical trials. Endocrinol Metab Suppl A 1994;1:43–49.
15.
Hankinson SE, Willett WC, Colditz GA, Hunter DJ, Michaud DS, Deroo B, Rosner B, Speizer FE, Pollak M: Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet 1998;351:1393–1396.
16.
Giovannucci E: Insulin-like growth factor-I and binding protein-3 and risk of cancer. Horm Res 1999;51(suppl 3):34–41.
17.
Grimberg A, Cohen P: Role of insulin-like growth factors and their binding proteins in growth control and carcinogenesis. J Cell Physiol 2000;183:1–9.
18.
Attanasio A, Attie K, Baxter R, Bengtsson BA, Black A, Blethen S, Carlsson L, Casaneuva F, Chipman J, Christiansen JS, Clemmons D, Cuneo R, De Rijdt D, Ghigo E, Hartman M, Hernberg-Stahl E, Hintz R, Garvan KH, Hoffman D, Irie M, Jorgensen JO, Kappelgaard AM, Laron Z, Malozowski S, Russell-Jones D, Shalet S, Sizonenko P, Sonksen PH, Strasburger C, Takano K, Thorner M: Consensus guidelines for the diagnosis and treatment of adults with growth hormone deficiency: Summary statement of the Growth Hormone Research Society Workshop on Adult Growth Hormone Deficiency. J Clin Endocrinol Metab 1998;83:379–381.
19.
Hasegawa Y, Hasegawa T, Takada M, Tsuchiya Y: Plasma free insulin-like growth factor I concentrations in growth hormone deficiency in children and adolescents. Eur J Endocrinol 1996;134:184–189.
20.
Juul A, Holm K, Kastrup KW, Pedersen SA, Michaelsen KF, Scheike T, Rasmussen S, Muller J, Skakkebaek NE: Free insulin-like growth factor I serum levels in 1,430 healthy children and adults, and its diagnostic value in patients suspected of growth hormone deficiency. J Clin Endocrinol Metab 1997;82:2497–2502.
21.
Graves DA: Utility of the National Cooperative Growth Study database for safety reporting. J Pediatr 1996;128(suppl):1–3.
22.
Sas TCJ, de Muinck Keizer-Schrama SMPF, Drop SLS: Dose dependent growth response of long-term growth hormone (GH) treatment in girls with Turner syndrome. Horm Res 1998;50(suppl 3):50.
23.
Tillmann V, Patel L, Gill MS, Whatmore AJ, Price DA, Kibirige MS, Wales JK, Clayton PE: Monitoring serum insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3), IGF-I/IGFBP-3 molar ratio and leptin during growth hormone treatment for disordered growth. Clin Endocrinol 2000;53:329–336.
24.
Ranke MB, Schwarze CP, Mohnike K, von Mühlendahl KE, Keller E, Willgerodt H, Kiess W: Catch-up growth after childhood-onset substitution in primary hypothyroidism: Is it a guide towards optimal growth hormone treatment in idiopathic growth hormone deficiency? Horm Res 1998;50:264–270.
25.
Schwarze CP, Wollmann HA, Binder G, Ranke MB: Short-term increments of insulin-like growth factor I (IGF-I) and IGF-binding protein-3 predict the growth response to growth hormone (GH) therapy in GH-sensitive children. Acta Paediatr Suppl 1999;428:200–208.
26.
Kristrom B, Carlsson B, Rosberg S, Carlsson LM, Albertsson-Wikland K: Short-term changes in serum leptin levels provide a strong metabolic marker for the growth response to growth hormone treatment in children. Swedish Study Group for Growth Hormone Treatment. J Clin Endocrinol Metab 1998;83:2735–2741.
27.
Rosenfeld RG: An endocrinologist’s approach to the growth hormone insulin-like growth factor axis. Acta Paediatr Suppl 1997;423:17–19.
28.
Ranke MB, Orskov H, Bristow AF, Seth J, Baumann G: Consensus on how to measure growth hormone in serum. Horm Res 1999;51(suppl):27–29.
29.
Quarmby V, Quan C, Ling V, Compton P, Canova-Davis E: How much insulin-like growth factor I (IGF-I) circulates? Impact of standardization on IGF-I assay accuracy. J Clin Endocrinol Metabol 1998;83:1211–1216.
30.
Baxter RC: Insulin-like growth factor binding proteins in the human circulation: A review. Horm Res 1994;42:140–144.
31.
Rajaram S, Baylink DJ, Mohan S: Insulin-like growth factor-binding proteins in serum and other biological fluids: Regulation and functions. Endocr Rev 1997;18:801–831.
32.
Clemmons DR, Snyder DK, Busby-WH J: Variables controlling the secretion of insulin-like growth factor binding protein-2 in normal human subjects. J Clin Endocrinol Metab 1991;73:727–733.
33.
Frystyk J, Skjærbaek C, Dinesen B, Orskov H: Free insulin-like growth factors (IGF-I and IGF-II) in human serum. FEBS Lett 1994;348:185–191.
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