IGF-1 and IGFBP 3 in Growth Hormone Deficiency Role of Insulin Like Growth Factor-1 (IGF-1) and IGF Binding Protein 3 in the Diagnosis of Growth Hormone Deficiency: Changing Paradigm

K Gayatri,Kd Modi,Pr Tripathy,S Jammula,Sk Kota

doi:10.3126/jnps.v32i2.5342

Abstract

GH stimulation tests are widely used in the diagnosis of GH deficiency (GHD), although they are associated with a high false positive rate. Serum IGF-I levels are monitored during GH replacement treatment in subjects with GH deficiency (GHD) to guide GH dose adjustment and to minimize occurrence of GHrelated side-effects. The need for reliance on provocative testing is based on evidence that the evaluation of spontaneous growth hormone (GH) secretion over 24 hours and the measurement of IGF-I and IGFBP-3 levels do not distinguish between normal and GHD subjects. Regarding IGF-I, it has been demonstrated that very low levels in patients highly suspected for GHD (i.e., patients with childhood-onset, severe GHD, or with multiple hypopituitarism acquired in adulthood) may be considered definitive evidence for severe GHD obviating the need for provocative tests. However, normal IGF-I levels do not rule out severe GHD and therefore adults suspected for GHD and with normal IGF-I levels must undergo a provocative test of GH secretion. We hereby review the various literatures at disposal justifying the use of IGF-1 and IGBP3 for diagnosis of growth hormone deficiency.Data Source: We searched PUBMED and MEDLINE database for relevant articles including key words. References of each article were further reviewed for final synthesis of the manuscript.J Nepal Paediatr Soc 2012;32(2):154-162 doi: http://dx.doi.org/10.3126/jnps.v32i2.5342

Highlights

Diagnosis of growth hormone (GH) deficiency (GHD) is still a matter of debate
Juul and Skakkebaek[31] concluded that measurement of Insulin-like growth factors (IGFs)-I was useful in the diagnosis of childhood GH deficiency (GHD) but, unlike the findings reported by Blum[30], more so in younger than older children
Low IGF-I and IGF-binding proteins (IGFBPs)-3 concentrations are reliable guides to the diagnosis of severe GHD, provided the investigator considers the alternative possibilities of malnutrition, hypothyroidism, liver disease, and GH insensitivity (GHI)

Summary

Introduction

Diagnosis of growth hormone (GH) deficiency (GHD) is still a matter of debate. Assuming that no clinical feature can be relied on as a guide, the approach to diagnosis must include a high index of suspicion of hypothalamic–pituitary disease. The use of IGF-l or IGF-BP3 in the diagnosis of GHD in children is a matter of controversy[5,6] because of variable sensitivity and specificity of these tests[5,7,8]. IGFBP3 is considered a good marker for the GH-IGF axis Both IGF-1 and IGF BP 3 are GH-regulated, but ageand nutrition-dependency often renders interpretation of results difficult, making it desirable for each laboratory to have its own normative data matched for age and body mass index (BMI). The percentage of children with normal stature who failed to attain a GH level greater than 7 μg/L in response to arginine, insulin and standardized treadmill exercise declined from 61% at pubertal stage 1 to 44% at stage 2, 11% at stage 3, and 0% at stages 4 and 5. The sensitivity and specificity of IGF-I in the diagnosis of GH deficiency in children is a matter of controversy because: 1. The liver is the principal source of IGF-I in the circulation

Hepatic production of IGF-I is highly influenced by nutritional factors

Findings

Conclusion