Background: Short stature is a main feature of Noonan syndrome (NS). Although rhGH is commonly used in NS patients, it is not known whether a defect in the secretion of GH influences the response to rhGH therapy.
Objective and hypotheses: The aim of this study was to evaluate the efficacy and safety of rhGH treatment in NS patients, according to the presence of GH deficiency at the baseline.
Method: We retrospectively collected data of 34 patients with NS (18 males, mean age 9.1±3.4 years, 28 of 34 prepubertal). Genetic test was positive in 27 cases (24 with PTPN11 mutation). Before starting treatment with rhGH, at an average dose of 0.031±0.005 mg/kg per day, patients undertook GH secretion test after stimulation. With normal secretion test (peak >8 ng/ml), rhGH was administered off-label. Growth was evaluated as change in height Z-score (Delta-Height-SDS) at one, two and three years after the start of therapy.
Results: At the baseline 13 patients had a deficiency of GH secretion (Def group: 7.9±3.3 years; mean height −3.06±1.00 SDS, mean GH peak 5.4±1.3 ng/ml), while 21 showed no failure (NoDef group: 9.7±3.2 years; −2.95±0.81 SDS, 10±2 ng/ml). After 1 year, therapy with rhGH was effective in improving linear growth in both groups (Delta-Height-SDS Def 0.53±0.40, P<0.001; NoDef 0.32±0.31, P<0.001). Between the two groups we found no significant difference in growth at 1, 2 and 3 years from baseline, although a tendency was present at the second year (Delta-Height-SDS Def 0.90±0.53; NoDef 0.53±0.49, P=0.06). As side effects, insulin resistance (HOMA-IR>2.5) was reported in 5 subjects (Def: 3, 23.1%; NoDef: 2, 9.5%).
Conclusion: Therapy with rhGH significantly increases growth in patients with Noonan syndrome, regardless of the initial presence of a GH deficiency and in the absence of significant side effects even in subjects with normal stimulation test.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology