Endocrine Abstracts

Objectives: Congenital heart disease, especially pulmonary stenosis, is a frequent comorbidity in patients with Noonan syndrome (NS). Patients with NS are also at increased risk of childhood leukaemia and solid tumours. Among solid tumours, brain tumours, including glioneuronal tumours, have been described in younger patients but remain rare. Current safety data do not indicate an association of growth hormone (GH) therapy with increased risk for development or progression of tumours or worsening of congenital cardiac conditions, but available data are limited. This report describes long-term real-world safety data on GH therapy in paediatric patients with NS.

Methods: Two complementary non-interventional, multicentre studies, NordiNet IOS (NCT00960128; n=154) and the ANSWER Program (NCT01009905; n=258), evaluated the long-term effectiveness and safety of Norditropin (somatropin; Novo Nordisk A/S, Denmark) as prescribed by treating physicians in a real-life clinical setting. Safety data (serious adverse events [SAEs] [not related to therapy], non-serious and serious adverse drug reactions [NSARs/SARs]) were evaluated for GH-treated patients with NS (n=412) enrolled in these studies.

Results: Baseline characteristics (% or mean [SD]): female, 29.1%; age at treatment start, 9.48 (3.92) years, height standard deviation score (SDS), −2.65 (0.95), weight SDS −2.03 (1.31), insulin-like growth factor-I (IGF-I) SDS, −1.13 (1.62), IGF binding protein−3 SDS, −0.91 (1.72), GH dose (μg/kg/day), 43.9 (13.7), GH-naïve, 68.5%. Mean (SD) treatment duration, 3.1 (2.6) years. GH dose (μg/kg/day), during treatment, 46.6 (13.6). The most common cardiovascular comorbidities reported included pulmonary valve stenosis (20 patients) and atrial septal defect (five patients). Overall, 31 adverse events (AEs) were reported in 21 patients (#events/#patients): NSARs, 21/15, SARs, 2/1, SAEs, 8/5. Most patients with AEs reported one event (16/21). For patients with AEs, mean (SD) age at treatment start was 9.90 (4.13) years and height SDS at baseline was −3.14 (0.82). The most common NSARs were headache (six events/six patients) and arthralgia (five events/three patients). Two SARs (brain neoplasm; metastases to spine) were reported in one patient. The SAEs reported were giant cell epulis (one patient), scoliosis and spinal fusion surgery (both in one patient), moyamoya disease (one patient), glioneuronal tumour (one patient), and aggravated glioneuronal tumour and epilepsy (one patient). No cardiac AEs were reported.

Conclusions: These data further support a favourable safety profile of GH therapy in patients with NS, specifically the absence of any cardiac AEs. Glioneuronal tumours have previously been associated with Noonan syndrome and RASopathies.