Impact of Growth Hormone Therapy on Adult Height in Patients with PTPN11 Mutations Related to Noonan Syndrome.

Abstract

OBJECTIVES:

The aim of this study was to evaluate the response to recombinant human growth hormone (rhGH) treatment in patients with Noonan syndrome (NS).

MATERIALS AND METHODS:

Forty-two patients (35 PTPN11+) were treated with rhGH, and 17 were followed-up until adult height. The outcomes were changes in growth velocity (GV) and height standard deviation scores (SDS) for normal (height-CDC SDS) and Noonan standards (height-NS SDS).

RESULTS:

The pretreatment chronological age was 10.3 ± 3.5 years. Height-CDC SDS and height-NS SDS were -3.1 ± 0.7 and -0.5 ± 0.6, respectively. PTPN11+ patients had a better growth response than PTPN11- patients. GV SDS increased from -1.2 ± 1.8 to 3.1 ± 2.8 after the first year of therapy in PTPN11+ patients, and from -1.9 ± 2.6 to -0.1 ± 2.6 in PTPN11- patients. The gain in height-CDC SDS during the first year was higher in PTPN11+ than PTPN11- (0.6 ± 0.4 vs. 0.1 ± 0.2, p = 0.008). Similarly, the gain was observed in height-NS SDS (0.6 ± 0.3 vs. 0.2 ± 0.2, respectively, p < 0.001). Among the patients that reached adult height (n = 17), AH-CDC SDS and AH-NS SDS were -2.1 ± 0.7 and 0.7 ± 0.8, respectively. The total increase in height SDS was 1.3 ± 0.7 and 1.5 ± 0.6 for normal and NS standards, respectively.

CONCLUSIONS:

This study supports the advantage of rhGH therapy on adult height in PTPN11+ patients. In comparison, PTPN11- patients showed a poor response to rhGH. However, this PTPN11- group was small, preventing an adequate comparison among different genotypes and no guarantee of response to therapy in genes besides PTPN11.

• Authors: Alexsandra C Malaquias, Renata M Noronha, Thaiana T O Souza, Thais K Homma, Mariana F A Funari, Guilherme L Yamamoto, Fernanda Viana Silva, Michelle B Moraes, Rachel S Honjo, Chong A Kim, Suzana Nesi-França, Julienne A R Carvalho, Elisangela P S Quedas, Debora R Bertola, Alexander A L Jorge
• Journal: Hormone research in paediatrics (Horm Res Paediatr) Vol. 91 Issue 4 Pg. 252-261 ( 2019) ISSN: 1663-2826 [Electronic] Switzerland
• PMID: 31132774 (Publication Type: Clinical Trial, Journal Article)
• Copyright: © 2019 S. Karger AG, Basel.

Chemical References

• Human Growth Hormone
• PTPN11 protein, human
• Protein Tyrosine Phosphatase, Non-Receptor Type 11

Topics

• Adult
• Body Height (drug effects, genetics)
• Female
• Human Growth Hormone (administration & dosage)
• Humans
• Longitudinal Studies
• Male
• Mutation
• Noonan Syndrome (drug therapy, genetics, physiopathology)
• Protein Tyrosine Phosphatase, Non-Receptor Type 11 (genetics)
• Retrospective Studies