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. 2018 May 21;16(3):e58928.
doi: 10.5812/ijem.58928. eCollection 2018 Jul.

Baseline IGFBP - 3 as the Key Element to Predict Growth Response to Growth Hormone and IGF - 1 Therapy in Subjects with Non - GH Deficient Short Stature and IGF - 1 Deficiency

Sheila Perez-Colon  1 , Oksana Lazareva  2 , Radhika Purushothaman  3 , Shahid Malik  4 , Svetlana Ten  5 , Amrit Bhangoo  6
Affiliations

Baseline IGFBP - 3 as the Key Element to Predict Growth Response to Growth Hormone and IGF - 1 Therapy in Subjects with Non - GH Deficient Short Stature and IGF - 1 Deficiency

Sheila Perez-Colon et al. Int J Endocrinol Metab. .

Abstract

Background: Short stature in children represents a heterogeneous group with different etiologies. Primary Insulin like growth factor 1 (IGF - 1) deficiency in short stature can present with normal or elevated growth hormone (GH) production. Currently there is no model that can reliably predict response to recombinant (r)GH therapy and/or rIGF - 1 therapy in children with non - GH deficient short stature.

Hypothesis: Baseline Insulin like growth factor binding protein 3 (IGFBP - 3) along with ∆ IGF - 1 in the first 3 months of GH therapy level can be a marker of growth response to the rGH and/or rIGF - 1 therapy in children with non - growth hormone deficiency short stature.

Objectives: To study the relationship between baseline IGFBP - 3 and IGF - 1 levels and the response to rGH and rIGF - 1 therapy in children with short stature, normal GH secretion and low IGF - 1 SDS.

Methods: 43 children, age 9.07 ± 2.75 years with height -2.72 ± 0.7 SD and baseline IGF - 1 of -2.76 ± 0.58 SD, who passed the growth hormone releasing hormone (GHRH) stimulation test were included in a retrospective chart review. They were treated with rGH therapy with a mean dose of 0.46 ± 0.1 mg/kg/week. Growth velocity (GV), IGF - 1 and IGFBP - 3 levels were done at 3 and 6 months of therapy. Subjects with poor response to rGH after 6 months of therapy were switched to rIGF - 1 therapy at 0.24 mg/kg/day for the next 6 months. Subjects were divided according to their growth rate into responders to rGH (N = 23); non - responders to rGH, responders to rIGF - 1 (N = 14) and non - responders to rGH and rIGF-1 (N = 6).

Results: There was no correlation between GV and peak GH level at GHRH test. Growth velocity positively correlated with ΔIGF - 1 SD among subjects treated with rGH therapy. Height SD positively correlated with IGFBP - 3 SD. Baseline IGFBP - 3 also inversely correlated with GH peak during GHRH test.

Conclusions: In subjects with short stature and low IGF - 1 level, baseline IGFBP - 3 levels can predict the growth response to rGH and/or rIGF - 1 therapy.

Keywords: Growth Hormone (GH); IGF - 1; IGFBP - 3; Short Stature; ΔIGF - 1.

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Figures

Figure 1.
Figure 1.. A: Correlation between Growth Velocity on r GH therapy and ΔIGF - 1 SDS. R as coefficient of Correlation. R = 0.37, P = 0.02. B: Correlation between growth velocity on rGH therapy and Baseline IGFBP - 3 SD. R = 0.47, P < 0.01. C: Correlation between height SD and baseline IGFBP - 3 SD. D: Correlation between baseline IGFBP - 3 SD with GH peak. R = 0.45, P = 0.02.
Figure 2.
Figure 2.. Algorithm for Management of Non - GH Deficient Short Stature with Low IGF - 1. Abbreviations: IGF-1, insulin-like growth factor-1; GH, growth hormone; IGFBP3, insulin-like growth factor binding protein 3; SDS, standard deviation score.
See this image and copyright information in PMC

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