Case Report: Possible improvement of near-adult height with PEG-rhGH and letrozole in a late-puberty boy with atypical Noonan syndrome and bone age/height age discrepancy: a novel therapy

Background Noonan syndrome (NS) is a rare congenital disorder predominantly characterized by short stature, with recombinant human growth hormone (rhGH) as the primary treatment. This study aimed to investigate the effects of a novel therapy involving pegylated (PEG)-rhGH and letrozole on near-adult height (NAH) improvement in a boy with NS who was undergoing late-puberty and presented with higher bone age (BA) than height age (HA). Case presentation We reported a 13-year-old boy with NS presented with subtle NS facial features, notable short stature and a higher BA than HA. His predicted adult height (PAH) was 163.3 cm (genetic target height: 178 cm). Following a therapeutic regimen of PEG-rhGH (2.3 years) and letrozole (1.7 years), his height increased by 9.7 cm in the first year, achieving an average growth rate of approximately 8.04 cm over a period of 2.3 years. The BA minus chronological age (CA) decreased from −0.33 to −1.50, indicating that letrozole slowed BA progression and prolonged the growth period. Ultimately, his NAH reached 172.1 cm, the PAH increased by 8.8 cm, and the height standard deviation score based on CA (HtSDS CA ) improved by 1.62. Additionally, there were no significant changes in thyroid function, blood glucose, uric acid, and IGF-1 levels during the treatment period, which fluctuated within the normal range. The patient had a transient slight elevation in testosterone, but normalized spontaneously, and the patient reported no discomfort. Besides, he experienced mild facial acne, but resolved without additional intervention after letrozole discontinuation. No other obvious adverse reactions were observed. Conclusion The novel therapy of PEG-rhGH and letrozole demonstrated promising potential in improving NAH, while adhering to safety profiles. This case represented the first attempt to use this dual therapy for NAH enhancement in an adolescent boy with NS and a higher BA than HA.