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IGF-I generation test in prepubertal children with Noonan syndrome due to mutations in the PTPN11 gene

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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. Patients: 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. Measurements: 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 (inter-quartiles 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.

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Authors and Affiliations

  1. Adolescent Medicine, I Pediatric Division, Department of Obstetrics, Gynecology and Pediatrics, Santa Chiara University Hospital, Via Roma, 67, 56126, Pisa, Italy

    Silvano Bertelloni MD, Giampiero I. Baroncelli & Silvia Ghione

  2. Division of Pediatric Oncology, Department of Obstetrics, Gynecology and Pediatrics, University Hospital, Pisa, Italy

    Eleonora Dati

  3. Laboratory of Medical Genetics, Department of Laboratory Medicine, University Hospital, Pisa, Italy

    Fulvia Baldinotti, Benedetta Toschi & Paolo Simi

Authors
  1. Silvano Bertelloni MD
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  2. Giampiero I. Baroncelli
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  3. Eleonora Dati
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  4. Silvia Ghione
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  5. Fulvia Baldinotti
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  6. Benedetta Toschi
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  7. Paolo Simi
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Correspondence to Silvano Bertelloni MD.

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Bertelloni, S., Baroncelli, G.I., Dati, E. et al. IGF-I generation test in prepubertal children with Noonan syndrome due to mutations in the PTPN11 gene. Hormones 12, 86–92 (2013). https://doi.org/10.1007/BF03401289

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  • DOI: https://doi.org/10.1007/BF03401289

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