{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T19:00:46Z","timestamp":1779217246920,"version":"3.51.4"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      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\u2005cm (genetic target height: 178\u2005cm). Following a therapeutic regimen of PEG-rhGH (2.3 years) and letrozole (1.7 years), his height increased by 9.7\u2005cm in the first year, achieving an average growth rate of approximately 8.04\u2005cm over a period of 2.3 years. The BA minus chronological age (CA) decreased from \u22120.33 to \u22121.50, indicating that letrozole slowed BA progression and prolonged the growth period. Ultimately, his NAH reached 172.1\u2005cm, the PAH increased by 8.8\u2005cm, and the height standard deviation score based on CA (HtSDS\n                      <jats:sub>CA<\/jats:sub>\n                      ) 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fped.2026.1643512","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T05:46:02Z","timestamp":1776059162000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["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"],"prefix":"10.3389","volume":"14","author":[{"given":"Zixia","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Genetics and Metabolism, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital Zhengzhou Children's Hospital","place":["Zhengzhou, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miaomiao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Genetics and Metabolism, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital Zhengzhou Children's Hospital","place":["Zhengzhou, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Genetics and Metabolism, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital Zhengzhou Children's Hospital","place":["Zhengzhou, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Genetics and Metabolism, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital Zhengzhou Children's Hospital","place":["Zhengzhou, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaqian","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Genetics and Metabolism, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital Zhengzhou Children's Hospital","place":["Zhengzhou, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengqin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Genetics and Metabolism, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital Zhengzhou Children's Hospital","place":["Zhengzhou, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linfei","family":"Li","sequence":"additional","affiliation":[{"name":"Henan Pediatric Clinical Research Center","place":["Zhengzhou, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongxing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Genetics and Metabolism, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital Zhengzhou Children's Hospital","place":["Zhengzhou, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1136\/archdischild-2021-322858","article-title":"Noonan syndrome: improving recognition and diagnosis","volume":"107","author":"Zenker","year":"2022","journal-title":"Arch Dis Child"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2034","DOI":"10.3390\/jcm11072034","article-title":"Growth, endocrine features, and growth hormone treatment in Noonan syndrome","volume":"11","author":"Dahlgren","year":"2022","journal-title":"J Clin Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/s0140-6736(12)61023-x","article-title":"Noonan syndrome","volume":"381","author":"Roberts","year":"2013","journal-title":"Lancet"},{"key":"B4","doi-asserted-by":"publisher","first-page":"e2266","DOI":"10.1002\/mgg3.2266","article-title":"Noonan syndrome: rhGH treatment and PTPN11 mutation","volume":"11","author":"Wu","year":"2023","journal-title":"Mol Genet Genomic Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1530\/eje-15-0922","article-title":"Growth patterns of patients with Noonan syndrome: correlation with age and genotype","volume":"174","author":"Cessans","year":"2016","journal-title":"Eur J Endocrinol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"951331","DOI":"10.3389\/fendo.2022.951331","article-title":"Inside the Noonan \u201cuniverse\": literature review on growth, GH\/IGF axis and rhGH treatment: facts and concerns","volume":"13","author":"Stagi","year":"2022","journal-title":". 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