7563 Investigation of the safety of GH treatment for Noonan syndrome -single center experience

Abstract Disclosure: M. Ishimaru: None. S. Fukui: None. E. Tanimoto: None. C. Nakamura: None. N. Ujita: None. H. Miyagi: None. H. Doi: None. M. Igarashi: None. T. Kashima: None. K. Yoshii: None. Y. Naiki: None. R. Horikawa: None. [Background] Growth hormone (GH) treatment for Noonan syndrome (NS) was approved in Japan in 2017. Although there have been no reports of serious adverse reactions associated with GH treatment for NS, there have been reports of myocardial thickening and warnings about malignant tumours which might be related to GH treatment. [Objective] To investigate the short- and long-term safety of GH treatment in patients with NS treated with GH at our hospital. [Methods and results] Medical records of 21 patients with NS (12 males and 9 females) treated with GH at our hospital from August 2006 to April 2023 were investigated retrospectively. Genetic diagnosis was performed in 13 patients, the others were clinically diagnosed. The patients ranged in age from 3 y 1 m to 11 y 6 m at the start of treatment, and the duration of treatment ranged from 11 m to 9 y 5 m. 2 patients had existing hypertrophic cardiomyopathy (HCM), and no patients experienced malignant neoplasmas or other hematologic abnormalities before treatment. The height was on average -3.60 SD at the start of treatment and had improved to an average of -2.10 SD at the most recent measurement. GH treatment was well-tolerated and no new severe adverse events were observed except for two who developed HCM after initiation of GH treatment. One patient developed HCM at the age of 17y and 0 m, 7 y 4 m after starting treatment. The treatment was continued in consultation with a cardiologist and completed at the age of 17 y and 4 m. Another patient was diagnosed as HCM 2 years and 3 months after the start of treatment. At the age of 7 y 2 m, 3 y 5 m after starting treatment, GH treatment was temporarily stopped by the cardiologist's decision. [Discussion] More than half of the children with Noonan syndrome have been reported to have short stature, indicating the effectiveness of GH treatment. Improvement of short stature has also been observed in our GH-treated cases. On the other hand, malignant tumours occur more frequently in NS and 50% of patients, with or without cardiomyopathy, are reported to have abnormal electrocardiograms. Long-term effect of GH and long-acting GH treatment on neoplasm formation and/or cardiac diseases should be carefully monitored. [Conclusion] The safety issues