Journal of Clinical Endocrinology & Metabolism, Vol 81, 2957-2962, Copyright © 1996 by Endocrine Society

ARTICLES

Proteolysis of insulin-like growth factor-binding protein-3 in human immunodeficiency virus-positive children who fail to thrive

RA Frost, SA Nachman, CH Lang and MC Gelato
Department of Medicine, State University of New York, Stony Brook 11794, USA.

Failure to thrive is a common manifestation of human immunodeficiency virus (HIV) infection in children. Given the role of insulin-like growth factor I (IGF-I) in stimulating postnatal growth, we have examined whether HIV-infected pediatric patients with growth failure have lower serum concentrations of IGF-I than age-matched control subjects. IGF-I was measured in 16 HIV-infected children and 13 HIV- negative controls. Ten of the HIV-infected children failed to thrive based on height and linear growth that was below the National Center for Health Statistics 10th percentile. IGF-I levels were significantly lower in children who failed to thrive compared to those in age-matched controls (20 vs. 60 micrograms/L; P < 0.001). Children who failed to thrive also displayed lower IGF-I levels than HIV-positive children, who exhibited normal growth velocity (20 vs. 91 micrograms/L; P < 0.001). Failure to thrive was associated with a significant reduction in circulating levels of IGF-binding protein-3 (IGFBP-3), as determined by ligand and Western blotting (P < 0.001), enhanced IGFBP-3 proteolysis (P < 0.001), and a decrease in the serum concentration of the acid-labile subunit of the IGFBP-3 ternary complex (P < 0.005). IGFBP-3 proteolysis was negatively correlated with IGF-I (r = 0.78) and IGFBP-3 levels (r = 0.70). Failure to thrive was associated with a reduction in the formation of the ternary complex, but the ternary complex could be restored by the addition of an excess of IGFBP-3 to serum. These results indicate that low levels of IGF-I, IGFBP-3, and acid-labile subunit are associated with a failure to thrive in HIV- infected children.

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