Increased IGFBP Proteolysis, IGF-I Bioavailability, and Pappalysin Levels in Children With Prader-Willi Syndrome.

CONTEXT

Prader-Willi syndrome (PWS) is associated with impaired growth hormone (GH) secretion and decreased insulin-like growth factor (IGF)-I levels. Pappalysins (PAPP-A, PAPP-A2) and stanniocalcins (STC-1, STC-2) regulate IGF binding-protein (IGFBP) cleavage and IGF bioavailability, but their implication in PWS is unknown.

OBJECTIVE

We determined serum levels of PAPP-As and STCs in association with IGF axis components in prepubertal and pubertal patients with PWS, also analyzing the effect of GH treatment.

METHODS

Forty children and adolescents with PWS and 120 sex- and age-matched controls were included. The effect of GH was evaluated at 6 months of treatment in 11 children.

RESULTS

Children with PWS had lower levels of total IGF-I, total and intact IGFBP-3, acid-labile subunit, intact IGFBP-4, and STC-1, and they had higher concentrations of free IGF-I, IGFBP-5, and PAPP-A. Patients with PWS after pubertal onset had decreased total IGF-I, total and intact IGFBP-3, and intact IGFBP-4 levels, and had increased total IGFBP-4, and STCs concentrations. GH treatment increased total IGF-I, total and intact IGFBP-3, and intact IGFBP-4, with no changes in PAPP-As, STCs, and free IGF-I levels. Standardized height correlated directly with intact IGFBP-3 and inversely with PAPP-As and the free/total IGF-I ratio.

CONCLUSION

The increase in PAPP-A could be involved in increased IGFBP proteolysis, promoting IGF-I bioavailability in children with PWS. Further studies are needed to establish the relationship between growth, GH resistance, and changes in the IGF axis during development and after GH treatment in these patients.