The authors concluded that Primary IGFD should be recognized as a diagnostic subset separate from idiopathic short stature.
"As knowledge of the molecular basis of growth improves, new categories for classifying short stature are needed, especially with the advent of new therapeutic strategies for growth disorders," said Cohen, director of pediatric endocrinology at Mattel Children's Hospital at UCLA.
Short stature is a relatively common condition estimated to affect 2 percent of the population. These children undergo a series of tests to evaluate the etiology of their growth problem, including testing of their growth hormone secretion using growth hormone stimulation tests and recently, measurement of the critical growth-promoting hormone, IGF-1. Children with growth hormone deficiency typically have low blood levels of IGF-1.
IGF-1 plays a principal role in stimulating growth and its deficiency can lead to short stature. Primary IGF-1 deficiency is characterized by abnormally low levels of IGF-1 in the presence of normal or elevated growth hormone levels. Most children with short stature are currently diagnosed as growth hormone deficient or idiopathic short stature and, irrespective of their diagnosis, are treated with recombinant human growth hormone replacement therapy.
Cohen presented data on the frequency of IGF-1 deficiency (IGFD) among patients currently classified as idiopathic short stature in a prospective, observational study of children referred for growth failure. The analysis was based on data from 6,447 children referred to 197 pediatric endocrine centers in the United States for evaluation of the hormonal basis of their short stature. Of these, 4,663 children were diagnosed with short stature.
The study, known as Sub-study 6 of the National Cooperative Growth Study, found that among IGF-1 deficient short stature patients, non-growth hormone deficient Primary IGFD was approximately as frequent as growth hormone deficiency itself. This relative prevalence suggests that approximately 30,000 children in the United States have short stature due to non-growth hormone deficiency, Primary IGFD. It also suggests that approximately one-third to one-half of idiopathic short stature children can be re-classified as Primary IGFD.
"We now know by using current diagnostic tools that IGF-1 deficiency is much more than an indicator of growth hormone deficiency and should be considered as a distinct diagnostic category," Cohen said. "In the future, studies should determine how the new diagnostic entity of IGFD should be approached with the expanding array of growth-promoting therapeutic agents and strategies."
Co-authors included Dr. Stephen Kemp, Arkansas Children's Hospital, Little Rock; Dr. Michael Kappy, The Children's Hospital, Denver; and Dr. David Wyatt, Medical College of Wisconsin, Milwaukee.
Cohen has served as a consultant for, and received honoraria from, Tercica, who sponsored the analysis of this study and received grant support from Genentech, who conducted the study.
UCLA's Mattel Children's Hospital is dedicated to the research, education and treatment of childhood diseases. The hospital's mission is to provide state-of-the-science treatment for children in a compassionate, family-oriented environment, as well as to conduct research to improve the understanding and treatment of pediatric diseases.