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Vascular endothelial growth factor (VEGF) levels in short, GH treated children: a distinct pattern of VEGF-C in
S Fuchs1,2, G Gat-Yablonski1,3,4, B Shtaif3,4
1The Jesse Z. and Sara Lea Shafer Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes, Schneider Children's Medical Center of Israel, 14 Kaplan Street, 49202, Petah Tikva, Israel.
Insights
Children with Noonan syndrome (NS) exhibit low baseline vascular endothelial growth factor-C (VEGF-C) and a diminished insulin-like growth factor-1 (IGF-1) response to growth hormone (GH) therapy. These findings suggest a unique growth factor profile in NS patients.
Area of Science:
- Pediatric Endocrinology
- Genetics and Rare Diseases
- Vascular Biology
Background:
- Noonan syndrome (NS) is a genetic disorder associated with short stature and an increased risk of lymphedema.
- Vascular endothelial growth factors (VEGFs) are implicated in the pathogenesis of lymphedema.
Observation:
- This study compared plasma insulin-like growth factor-1 (IGF-1), VEGF-A, and VEGF-C levels in children with NS versus short, GH-sufficient children.
- Measurements were taken before and during growth hormone (GH) treatment.
Findings:
- Noonan syndrome patients had lower baseline VEGF-C levels and a significantly blunted IGF-1 response to GH compared to controls.
- VEGF-A levels were similar at baseline, and neither VEGF-A nor VEGF-C levels changed significantly during GH treatment.
- No correlation was observed between VEGF-C and IGF-1, VEGF-A, or auxological parameters.
Implications:
- Children with NS present with a distinct endocrine and growth factor profile, characterized by low basal VEGF-C and impaired IGF-1 response to GH.
- Further research is warranted to explore the relationship between VEGF-C levels and lymphedema in Noonan syndrome.
- These findings may inform future therapeutic strategies for managing growth and potential vascular complications in NS.
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.
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