Abstract
Until recently, the only possible therapy available for treatment of children with significant short stature was recombinant human growth hormone (rhGH). However, recombinant human insulin-like growth factor-I (rhIGF-I) has now become commercially available as a therapeutic option to treat children of short stature caused by severe primary IGF-I deficiency, defined as: height standard deviation score (SDS) less than or equal to −3.0, basal IGF-I SDS less than or equal to −3.0, and normal or elevated levels of GH. Published data demonstrate that rhIGF-I therapy in patients with primary IGF-I deficiency accelerates growth significantly during the first year of treatment, but progressive attenuation is likely in subsequent years. The growth response to rhIGF-I is neither as intense nor as well sustained as the growth response to rhGH among children with GH deficiency. Despite increasing interest in the possibility for broader use of rhIGF-I for growth promotion, especially in children with idiopathic short stature (ISS), it is necessary to wait for studies assessing the efficacy and safety of rhIGF-I therapy in this condition. In this particular population (ISS patients), the combination of rhIGF-I and rhGH, compared with either hormone used alone, may have theoretical advantages. Hypoglycemia has been the most common side effect reported with use of rhIGF-I and is reasonably controlled with adequate food intake. Most of the other (long-term) adverse effects appear to be related to hyperstimulation of lymphoid tissue growth. Little is known about the long-term effects of IGF-I therapy in growing children, but caution and long-term, controlled, prospective trials of rhIGF-I-treated children and adolescents are needed.
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Lewis UJ, Singh RN, Tutwiler GF, Sigel MB, VanderLaan EF, VanderLaan WP. Human growth hormone: a complex of proteins. Recent Prog Horm Res. 1980;36:477–508.
Frohman LA. Neurotransmitters as regulators of endocrine function. In: Krieger DT, Hughes JC, eds. Neuroendocrinology. Sunderland, MA: Sinauer Associates; 1980:44–57.
Nilsson O, Marino R, De Luca F, Phillip M, Baron J. Endocrine regulation of the growth plate. Horm Res. 2005;64:157–165.
Ohlsson C, Bengtsson BA, Isaksson OG, Andreassen TT, Slootweg MC. Growth hormone and bone. Endocr Rev. 1998;19:55–79.
Rajaram S, Baylink DJ, Mohan S. Insulinlike growth factor-binding proteins in serum and other biological fluids: regulation and functions. Endocr Rev. 1997;18:801–831.
Baxter RC. Insulin-like growth factor binding proteins in the human circulation: a review. Horm Res. 1994;42:140–144.
Le Roith D. The insulin-like growth factor system. Experimental Diab Res. 2003;4:205–212.
Collett-Solberg PF, Cohen P. The role of the insulin-like growth factor binding proteins and the IGFBP proteases in modulating IGF action. Endocrinol Metab Clin North Am. 1996;25:591–614.
Ranke MB, Schweizer R, Lindberg A, et al Insulin-like growth factors as diagnostic tools in growth hormone deficiency during childhood and adolescence: the KIGS experience. Horm Res. 2004;62:17–25.
Jensen RB, Jeppesen KA, Vielwerth S, et al Insulin-like growth factor I (IGF-I) and IGF-binding protein 3 as diagnostic markers of growth hormone deficiency in infancy. Horm Res. 2005;63:15–21.
Hasegawa Y, Hasegawa T, Aso T, et al Usefulness and limitation of measurement of insulin-like growth factor binding protein-3 (IGFBP-3) for diagnosis of growth hormone deficiency. Eur J Endocrinol. 1992;39:585–591.
Smith WJ, Underwood LE, Busby WH, et al Use of insulin-like growth factor-binding protein-2 (IGFBP-2), IGFBP-3, and IGF-I for assessing growth hormone status in short children. J Clin Endocrinol Metab. 1993;77:1294–1299.
Buckway CK, Selva KA, Pratt KL, Tjoeng E, Guevara-Aguirre J, Rosenfeld RG. Insulinlike growth factor binding protein-3 generation as a measure of GH sensitivity. J Clin Endocrinol Metab. 2002;87:4754–4765.
Selva KA, Buckway CK, Sexton G, et al Reproducibility in patterns of IGF generation with special reference to idiopathic short stature. Horm Res. 2003;60:237–246.
Laron Z, Klinger B. Laron syndrome: clinical features, molecular pathology and treatment. Horm Res. 1994;42:198–202.
Increlex® (mecasermin) US prescribing information. Available at: www.tercica.com. Accessed October 14, 2008.
Iplex™ (mecasermin rinfabate) prescribing information. Available at: www.insmed.com. Accessed October 14, 2008.
Ranke MB, Savage MO, Chatelain PG, Preece MA, Rosenfeld RG, Wilton P. Long-term treatment of growth hormone insensitivity syndrome with IGF-I. Results of the European Multicentre Study. The Working Group on Growth Hormone Insensitivity Syndromes. Horm Res. 1999;51:128–134.
Chernausek SD, Backeljauw PF, Frane J, Kuntze J, Underwood LE. GH Insensitivity Syndrome Collaborative Group. Long-term treatment with recombinant insulin-like growth factor (IGF)-I in children with severe IGF-I deficiency due to growth hormone insensitivity. J Clin Endocrinol Metab. 2007;92:902–910.
Backeljauw PF, Underwood LE. Therapy for 6.5-7.5 years with recombinant insulin-like growth factor-I in children with growth hormone insensitivity syndrome: a clinical research center study. J Clin Endocrinol Metab. 2001;86:1504–1510.
Guevara-Aguirre J, Rosenbloom AL, Vasconez O, et al Two-year treatment of growth hormone (GH) receptor deficiency with recombinant insulin-like growth factor I in 22 children: comparison of two dosage levels and to GH-treated GH deficiency. J Clin Endocrinol Metab. 1997;82:629–633.
Klinger B, Laron Z. Three year IGF-I treatment of children with Laron syndrome. J Pediatr Endocrinol Metab. 1995;8:149–158.
Midyett LK, Rogol A, Frane J, Bright G. Efficacy and safety of twice-daily rhIGF-I treatment in prepubertal children with primary IGF-I deficiency: results from a randomized clinical trial. Abstract presented at: International Congress of Endocrinology; November 8–12, 2008; Rio de Janerio.
Guevara-Aguirre J, Guevara-Aguirre M, Rosenbloom AL. Absence of hypoglycemia in response to varying doses of recombinant human insulin-like growth factor-I (rhIGF-I) in children and adolescents with low serum concentrations of IGF-I. Acta Paediatr. 2006;95:199–202.
Guevara-Aguirre J, Vasconez O, Martinez V, et al A randomized, double blind, placebocontrolled trial on safety and efficacy of recombinant human insulin-like growth factor-I in children with growth hormone receptor deficiency. J Clin Endocrinol Metab. 1995;80:1393–1398.
Laron Z, Ginsberg S, Lilos P, Arbiv M, Vaisman N. Long-term IGF-I treatment of children with Laron syndrome increases adiposity. Growth Horm IGF Res. 2006;16:61–64.
Vasconez O, Martinez V, Martinez AL, et al Heart rate increases in patients with growth hormone receptor deficiency treated with insulin-like growth factor I. Acta Paediatr Suppl. 1994;399:137–139.
Camacho-Hübner C, Rose S, Preece MA, et al Pharmacokinetic studies of recombinant human insulin-like growth factor I (rhIGF-I)/rhIGF-binding protein-3 complex administered to patients with growth hormone insensitivity syndrome. J Clin Endocrinol Metab. 2006;91: 1246–1253.
Camacho-Hübner C, Underwood LE, Yordam N, et al Once daily rhIGF-I/rhIGFBP-3 treatment improves growth velocity in children with severe primary IGF-I deficiency: result of a multi-center clinical trial. Abstract presented at: 88th Annual Meeting of The Endocrine Society; June 24–28, 2006; Boston, MA, USA. Abstract OR 40-1.
Rosenfeld RG, Hwa V. New molecular mechanisms of GH resistance. Eur J Endocrinol. 2004;151(suppl. 1):S11–S15.
Limal JM, Parfait B, Cabrol S, et al Noonan syndrome: relationships between genotype, growth, and growth factors. J Clin Endocrinol Metab. 2006;91:300–306.
Clark RG. Recombinant insulin-like growth factor-1 as a therapy for IGF-1 deficiency in renal failure. Pediatr Nephrol. 2005;20: 290–294.
Park P, Cohen P. Insulin-like growth factor I (IGF-I) measurements in growth hormone (GH) therapy of idiopathic short stature (ISS). Growth Horm IGF Res. 2005;15(suppl. A):S13–S20.
Riedl S, Frisch H. Effects of growth hormone (GH) and insulin-like growth factor I in patients with gene defects in the GH axis. J Pediatr Endocrinol Metab. 2006;19: 229–236.
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Richmond, E.J., Rogol, A.D. Recombinant human insulin-like growth factor-I therapy for children with growth disorders. Adv Therapy 25, 1276–1287 (2008). https://doi.org/10.1007/s12325-008-0124-9
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DOI: https://doi.org/10.1007/s12325-008-0124-9