Reproducibility in Patterns of IGF Generation with Special Reference to Idiopathic Short Stature

Abstract

Background/Aim: Insulin-like growth factor I (IGF-I) and insulin-lke growth factor binding protein 3 (IGFBP-3) generation tests are both sensitive and specific measures of growth hormone (GH) sensitivity. Recently, the question of reproducibility of IGF generation tests has been raised. We report our analysis of the correlation of low- and high-dose GH IGF-I and IGFBP-3 generation tests among patients with GH deficiency, GH insensitivity, and idiopathic short stature. Methods: A total of 198 subjects were randomized to either high- or low-dose GH for 7 days; the alternate dose was received after a 2-week washout period. Samples were collected at baseline and on days 5 and 8 of GH administration. Results: The serum concentrations of IGF-I and IGFBP-3 correlated significantly from one test to the other, regardless of the diagnosis. In normal subjects and patients with GH insensitivity and GH deficiency, the delta over baseline in IGF-I and IGFBP-3 in the low-dose test was highly predictive of the delta values in the high-dose test. The delta correlation was greatly diminished, however, in the patient population having idiopathic short stature. Conclusions: These observations support partial GH insensitivity effecting IGF-I generation specifically, as a possible etiology for idiopathic short stature, and thus such patients may warrant appropriate biochemical and/or molecular evaluation for partial GH insensitivity.

The insulin-like growth factor-I (IGF-I) generation test as an indicator of growth hormone status

“…41,42 In contrast, another study showed that in 16 ISS patients with normal baseline IGF-I levels there was a lower than normal IGF-I response on days 5 and 8 of a 7-day IGF-I gen, pos-sibly indicating a partial GH insensitivity. 25 Another study showed that the IGF-I response 24 hours after a single injection of hGH (2 mg/m 2 ) given to 22 prepubertal ISS children was comparable to that of the control children whose mean height though was -1.2 SD. 43 The criteria for classifying the children as ISS in these studies was only that they were short (height < -2SD) and had a normal GH response to pharmacologic provocation.…”

“…[18][19][20][21][22][23][24] It is an invaluable test for diagnosing GHI with a high reproducibility in adults and children. 25 The IGF-I gen has also been used to investigate the relationship between the IGF-I gen response and the growth responses during hGH therapy in children with GH deficiency diagnosed by pharmacologic provocation testing. Rudman et al 26 first studied the IGF I response after a therapeutic trial of ten days with hGH in GHD patients and found a robust increase of IGF-I after a few days of hGH treatment.…”

GH responsiveness varies during the menstrual cycle

“…There is evidence of significant correlation in IGF-1 and IGFBP-3 responses in individuals undergoing sequential IGF-1 generation tests (12).…”

Profile of mecasermin for the long-term treatment of growth failure in children and adolescents with severe primary IGF-1 deficiency

“…22 However, a positive response to the test can be considered an increment of IGF-1 or IGFBP-3 more than twice the coefficient of variation of the assay used. 23 The test identifies almost all the forms of primary GHI.…”