Vascular endothelial growth factor (VEGF) levels in short, GH treated children: a distinct pattern of VEGF-C in Noonan syndrome.

CONTEXT

Noonan syndrome (NS) is characterized by short stature and elevated risk of lymphedema. The mechanism underlying lymphedema may be mediated by vascular endothelial growth factors (VEGFs).

OBJECTIVE

To assess the effect of growth hormone (GH) treatment on plasma insulin-like growth factor (IGF)-1, VEGF-A and VEGF-C levels in patients with NS as compared to short GH-sufficient children.

DESIGN

Retrospective, comparative.

SETTING

Endocrinology department of a tertiary pediatric medical center.

PATIENTS AND METHODS

Plasma IGF-1, VEGF-A and VEGF-C levels were measured before and during GH treatment in 6 patients with NS and 18 age-matched short subjects (Turner, idiopathic short stature and small for gestational age).

MAIN OUTCOME MEASURES

Changes in plasma VEGF and IGF-1 levels.

RESULTS

Baseline IGF-1 SDS levels were slightly lower in NS patients compared with controls; IGF-1 response to GH therapy was markedly lower in NS patients compared with controls (p = 0.017). Mean baseline VEGF-A levels were similar in NS patients and controls whilst mean baseline VEGF-C levels were significantly lower in the NS group as compared with controls (p = 0.022). Plasma VEGF-A and VEGF-C levels did not significantly change during GH treatment in the study cohort. No correlation was found between VEGF-C levels and levels of IGF-1, VEGF-A and auxological parameters, either before or during GH administration.

CONCLUSION

Children with NS have a distinct growth factor profile including low basal VEGF-C and flattened IGF-1 response to GH. Further studies are needed to confirm our findings and to elucidate the interaction between VEGF-C levels and lymphedema.