Cardiovascular Safety of Growth Hormone Treatment in Noonan Syndrome: Real-World Evidence

Authors

Alicia Romano, Department of Pediatrics, New York Medical College, Valhalla, New York, USA.
Juan Pablo Kaski, Centre for Inherited Cardiovascular Diseases, Great Ormond Street Hospital & UCL Institute of Cardiovascular Science, London, UK.
Jovanna Dahlgren, Department of Paediatrics, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.
Nicky Kelepouris, US Medical Affairs, Novo Nordisk Inc., Plainsboro, New Jersey, USA.
Alberto Pietropoli, Global Medical Affairs, Novo Nordisk Health Care AG, Zurich, Switzerland.
Tilman R. Rohrer, Department of Pediatric Endocrinology, University Children's Hospital, Saarland University Medical Center, Homburg, Germany.
Michel Polak, Paediatric Endocrinology, Diabetology and Gynaecology Department, Hôpital Universitaire Necker Enfants-Malades, AP-HP, Université de Paris, Imagine Institute, Paris, France.

Author Type(s)

Faculty

DOI

10.1530/EC-21-0549

Journal Title

Endocrine Connections

Document Type

Article

Publication Date

1-31-2022

Department

Pediatrics

Abstract

OBJECTIVE: The study aims to assess the cardiovascular safety of growth hormone (GH) treatment in patients with Noonan syndrome (NS) in clinical practice. DESIGN: The study design involves two observational, multicentre studies (NordiNet® IOS and the ANSWER Program) evaluating the long-term effectiveness and safety of GH in >38,000 paediatric patients, of which 421 had NS. METHODS: Serious adverse events, serious adverse reactions (SARs) and non-serious adverse reactions (NSARs) were reported by the treating physicians. Cardiovascular comorbidities at baseline and throughout the studies were also recorded. RESULTS: The safety analysis set comprised 412 children with NS (29.1% females), with a mean (s.d.) baseline age of 9.29 (3.88) years, treated with an average GH dose of 0.047 (0.014) mg/kg/day during childhood. Cardiovascular comorbidities at baseline were reported in 48 (11.7%), most commonly pulmonary valve stenosis (PVS) and atrial septal defects. Overall, 22 (5.3%) patients experienced 34 safety events. The most common were the NSARs: headache (eight events in seven patients) and arthralgia (five events in three patients). Two SARs occurred in one patient (brain neoplasm and metastases to spine). No cardiovascular safety events were recorded in patients with NS. Five cardiovascular comorbidities in five patients were reported after initiation of GH treatment: three cases of unspecified cardiovascular disease, one ruptured abdominal aortic aneurysm and one PVS. CONCLUSIONS: GH treatment had a favourable safety profile in patients with NS, including those with cardiovascular comorbidities. Prospective studies are warranted to systematically assess the safety of GH treatment in patients with NS and cardiovascular disease.

Recommended Citation

Romano, A., Kaski, J. P., Dahlgren, J., Kelepouris, N., Pietropoli, A., Rohrer, T. R., & Polak, M. (2022). Cardiovascular Safety of Growth Hormone Treatment in Noonan Syndrome: Real-World Evidence. Endocrine Connections, 11 (1). https://doi.org/10.1530/EC-21-0549