ESPE Abstracts

Introduction: Noonan syndrome (NS) is relatively common genetic disorder caused by mutations in the PTPN11 (50%), SOS1 (10-13%), and RAF1 (3-17%) genes responsible for disturbances in the activation of the RAS/MAPK signaling pathway. NS is characterized by facial dysmorphic features (90%), congenital cardiac disturbances and short stature (<3c) - the average final adult height is 162.5 cm for male and 153 cm for female. In some, but not all of the NS patients, growth hormone deficiency is observed. Considering the literature, growth hormone replacement therapy (GRHT) improves the final height in this patients whereas the treatment remains safe. However, long-term follow-up concerning the growth rate, final height (FH) and puberty process in NS patients is still to be obtained. The objectives of this work is to reveal GHRT outcomes in patients with long-term follow-up.

Patients and methods: This is a retorspective study of three patient cases conducted in the Department of Endocrinology and Metabolic Diseases in Polish Mother's Memorial Hospital - Research Institute in Lodz (Poland) over a period of 3,5-9 years, from June 2013 to February 2023.

Results: We collected 3 NS patients with PTPN11 gene mutation and growth hormone deficiency (GHD) treated with GHRT for 3.5, 8 and 9 years. The onset of GHRT occurred with a median age of 8.3 years. In all cases height SD score (HSDS) during treatment improved (ΔHSDS mean±SD: 1.6±0.67; min-max: 1,08-2,27). In one patient near FH was obtained consistent with the target height (TH). In two patients rapid bone age (BA) advancement and deteriorating growth prognosis lead to pharmacological inhibition of sexual maturation and epiphyseal ossification. In the last two cases the final results are uncertain despite current improvement.

Conclusion: GHRT improved growth outcome in NS patients, however the final results depends on various factors, thus demands personalized therapy.