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Insulin-like growth factor-I deficiency in children with growth hormone insensitivity: current and future treatment options.
BioDrugs. 2009; 23(3):155-63.B

Abstract

Growth hormone (GH) acts directly at the growth plate and through the production of insulin-like growth factor (IGF)-I. At least 50% of the hormone circulates bound to GH binding protein, and its secretion is controlled by growth hormone-releasing hormone and somatostatin. Once GH binds to two GH receptors, the janus activated kinase/signal transducers and activators of transcription (JAK/STAT) protein pathway is activated, resulting in the production of IGF-I. Serum IGF-I is produced predominantly in the liver and circulates in a 140 kDa complex, along with its binding protein, IGF binding protein 3, and acid-labile protein. Recombinant human (rh) IGF-I (mecasermin) is approved by the US FDA and the European Medicines Agency for the treatment of patients with severe primary IGF deficiency or for patients with GH1 gene deletion who have developed neutralizing antibodies to GH. It has been shown to increase growth velocity in children with either condition. In the past, there have been adverse events, particularly hypoglycemia, reported with the administration of mecasermin. However, a recent report of long-term therapy with mescasermin in children with severe IGF-I deficiency has concluded that although adverse events are common, they are rarely severe enough to interrupt or modify treatment. The serum half-life of mecasermin is shorter in patients with GH insensitivity syndrome and low serum levels of its binding protein, the insulin-like growth factor binding protein (IGFBP)-3 and acid-labile subunit, compared with the serum half-life in normal volunteers or in patients with an IGF1 gene deletion who have normal levels of IGFBP-3. Mecasermin rinfabate, a complex of rhIGF-I and rhIGFBP-3, appears to prolong the serum half-life and might counteract acute adverse events, particularly hypoglycemia, associated with the administration of mescasermin. Mecasermin rinfabate, however, is no longer available in the USA or Europe for treating conditions involving short stature, because of a legal requirement. Mecasermin has been shown to be effective in increasing height velocity and adult height in patients with severe GH resistance and in IGF1 gene deletion. There has been some interest in using mecasermin to treat patients with partial GH resistance or idiopathic short stature. At the present time, the data are insufficient to make this recommendation.

Authors+Show Affiliations

Section of Endocrinology, University of Arkansas for Medical Sciences at Arkansas Children's Hospital, Little Rock, AR 72202, USA. KempStephenF@uams.edu

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

19627167

Citation

Kemp, Stephen F.. "Insulin-like Growth factor-I Deficiency in Children With Growth Hormone Insensitivity: Current and Future Treatment Options." BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy, vol. 23, no. 3, 2009, pp. 155-63.
Kemp SF. Insulin-like growth factor-I deficiency in children with growth hormone insensitivity: current and future treatment options. BioDrugs. 2009;23(3):155-63.
Kemp, S. F. (2009). Insulin-like growth factor-I deficiency in children with growth hormone insensitivity: current and future treatment options. BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy, 23(3), 155-63. https://doi.org/10.2165/00063030-200923030-00002
Kemp SF. Insulin-like Growth factor-I Deficiency in Children With Growth Hormone Insensitivity: Current and Future Treatment Options. BioDrugs. 2009;23(3):155-63. PubMed PMID: 19627167.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Insulin-like growth factor-I deficiency in children with growth hormone insensitivity: current and future treatment options. A1 - Kemp,Stephen F, PY - 2009/7/25/entrez PY - 2009/7/25/pubmed PY - 2009/10/17/medline SP - 155 EP - 63 JF - BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy JO - BioDrugs VL - 23 IS - 3 N2 - Growth hormone (GH) acts directly at the growth plate and through the production of insulin-like growth factor (IGF)-I. At least 50% of the hormone circulates bound to GH binding protein, and its secretion is controlled by growth hormone-releasing hormone and somatostatin. Once GH binds to two GH receptors, the janus activated kinase/signal transducers and activators of transcription (JAK/STAT) protein pathway is activated, resulting in the production of IGF-I. Serum IGF-I is produced predominantly in the liver and circulates in a 140 kDa complex, along with its binding protein, IGF binding protein 3, and acid-labile protein. Recombinant human (rh) IGF-I (mecasermin) is approved by the US FDA and the European Medicines Agency for the treatment of patients with severe primary IGF deficiency or for patients with GH1 gene deletion who have developed neutralizing antibodies to GH. It has been shown to increase growth velocity in children with either condition. In the past, there have been adverse events, particularly hypoglycemia, reported with the administration of mecasermin. However, a recent report of long-term therapy with mescasermin in children with severe IGF-I deficiency has concluded that although adverse events are common, they are rarely severe enough to interrupt or modify treatment. The serum half-life of mecasermin is shorter in patients with GH insensitivity syndrome and low serum levels of its binding protein, the insulin-like growth factor binding protein (IGFBP)-3 and acid-labile subunit, compared with the serum half-life in normal volunteers or in patients with an IGF1 gene deletion who have normal levels of IGFBP-3. Mecasermin rinfabate, a complex of rhIGF-I and rhIGFBP-3, appears to prolong the serum half-life and might counteract acute adverse events, particularly hypoglycemia, associated with the administration of mescasermin. Mecasermin rinfabate, however, is no longer available in the USA or Europe for treating conditions involving short stature, because of a legal requirement. Mecasermin has been shown to be effective in increasing height velocity and adult height in patients with severe GH resistance and in IGF1 gene deletion. There has been some interest in using mecasermin to treat patients with partial GH resistance or idiopathic short stature. At the present time, the data are insufficient to make this recommendation. SN - 1179-190X UR - https://www.unboundmedicine.com/medline/citation/19627167/Insulin_like_growth_factor_I_deficiency_in_children_with_growth_hormone_insensitivity:_current_and_future_treatment_options_ L2 - https://dx.doi.org/10.2165/00063030-200923030-00002 DB - PRIME DP - Unbound Medicine ER -