title: IGF-I generation test in prepubertal children with Noonan syndrome due to mutations in the PTPN11 gene.
abstract: BACKGROUND
  Short stature represents one of the main features of children with Noonan syndrome. The reason for impaired growth remains largely unknown.
  
  
  OBJECTIVE
  To assess GH and IGF1 secretion in children with Noonan syndrome.
  
  
  METHODS
  12 prepubertal children with Noonan syndrome due to mutations in the PTPN11 gene [7 males, 6 females; median age, years: 8.6 (range 5.1-13.4)] were studied; 12 prepubertal children with short stature (SS) [7 males, 5 females; median age, years: 8.1 (range 4.8-13.1)] served as the control group.
  
  
  METHODS
  GH secretion after arginine stimulation test; IGF1 generation test by measurement of IGF1 levels before and after recombinant GH (rGH) administration (0.05 mg/kg/day for 4 days).
  
  
  RESULTS
  Baseline and stimulated peak values of GH were not significantly different between the two groups. At +120 minutes, GH levels remained significantly higher (p = 0.0121) in comparison with baseline values in children with Noonan syndrome. Baseline IGFI levels in patients and in SS controls were not significantly different, in contrast to values after the rGH generation test [205 ng/mL (interquartiles 138.2-252.5 ng/mL) and 284.5 ng/mL (interquartiles 172-476 ng/mL), respectively; p = 0.0248]. IGF1 values were significantly related to height (baseline: r = 773, p = 0.0320; peak: r = 0.591, p = 0.0428) in children with Noonan syndrome.
  
  
  CONCLUSIONS
  Blunted increase of IGF1 after the rGH generation test was present in children with Noonan syndrome due to mutations in the PTPN11 gene in comparison with SS children. This finding may be due to partial GH resistance in the former likely related to altered Ras-MAPK signaling pathway.
authors.affiliation: Adolescent Medicine, I Pediatric Division, Department of Obstetrics, Gynaecology and Pediatrics, University Hospital, Pisa, Italy. s.bertelloni@ao-pisa.toscana.it
authors.forename: Silvano
authors.initials: S
authors.lastname: Bertelloni
authors.forename: Giampiero I
authors.initials: GI
authors.lastname: Baroncelli
authors.forename: Eleonora
authors.initials: E
authors.lastname: Dati
authors.forename: Silvia
authors.initials: S
authors.lastname: Ghione
authors.forename: Fulvia
authors.initials: F
authors.lastname: Baldinotti
authors.forename: Benedetta
authors.initials: B
authors.lastname: Toschi
authors.forename: Paolo
authors.initials: P
authors.lastname: Simi
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D001827:Body Height / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D003940:Diagnostic Techniques, Endocrine; D005260:Female; D020022:Genetic Predisposition to Disease; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D009154:Mutation; D009634:Noonan Syndrome / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D010641:Phenotype; D011237:Predictive Value of Tests; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics*; D046468:Sexual Development; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C583557:IGF1 protein, human; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11