Role of IGF-1 in the Treatment of Growth Failure

Insulin-like growth factor 1 (IGF-1) is a potent growth and differentiation factor. It stimulates the multiple processes leading to statural growth and is normally secreted in response to stimulation by growth hormone (GH). IGF-1 deficiency (IGFD) can be caused by abnormalities of either the GH receptor or the GH signaling pathway. Patients with severe primary IGF-1 deficiency (Primary IGFD) fail to produce adequate levels of IGF-1, due to disruption of the GH pathway used to promote IGF-1 release (possibly due to mutations in the GH receptor [GHR], post-GHR signaling pathway, and/or IGF-1 gene defects). Severe primary IGFD is defined by 1) height standard deviation score less than or equal to -3.0, 2) basal IGF-1 standard deviation score less than or equal to -3.0, and 3) normal or elevated GH The deficiency can lead to a range of other metabolic disorders, including lipid abnormalities, decreased bone density, obesity and insulin resistance.

Administering exogenous GH does not address all GH-related disorders, especially severe primary IGFD. Though GH exerts direct effects on target tissues, many of its physiologic effects are mediated indirectly through IGF-1. Resistance to GH is linked with various types of homozygous or heterozygous GH receptor (GHR) mutations, as well as molecular defects in the post-growth hormone receptor signaling cascade. Researchers are still trying to understand the impact and specific nature of these gene-based mutations. Because IGF-1 is a critical factor in the growth of children, the availability of recombinant IGF-1 (rhIGF-1) has dramatically changed the long-term prognosis for children with IGFD. When treatment is ongoing, exogenous rhIGF-1 exerts an anabolic effect that enhances protein synthesis and stimulates growth.

In this conversation, two pediatric endocrinology specialists, Dr. Naomi Neufeld and Dr. Paul Saenger, join Dr. Carlos Hamilton, Jr. to discuss current issues surrounding the role of IGF-1 in the treatment of growth failure.

Related References/Reading:

  1. Slides reprinted with permission of IGFDForum.com. “Growth Axis: The Primary Pathway” and “Short Stature Due to Severe Primary IGF Deficiency”. Available at http://www.igfdforum.com. Accessed December 6, 2007.
  2. Chernausek SD, Backeljauw PF, Frane J, et al. 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.
  3. Laron Z. Laron syndrome (primary growth hormone resistance or insensitivity): the personal experience 1958-2003. J Clin Endocrinol Metab. 2004;89(3):1031-44.
  4. Rosenbloom AL. The role of recombinant insulin-like growth factor I in the treatment of the short child. Current Opinion in Pediatrics 2007;19:458–464.