Real-World Effectiveness and Safety of Recombinant Human Growth Hormone in Chinese Children with Noonan Syndrome: Long-Term Follow-up and a 2-Year Comparison of Short- and Long-Acting Formulations

Abstract: This retrospective real-world cohort study evaluated the effectiveness and safety of recombinant human growth hormone therapy in Chinese children with Noonan syndrome, with a predefined comparison between short-acting growth hormone and long-acting growth hormone during the first 2 years of treatment. Twenty children with Noonan syndrome were included; 16 were boys, and the median age at recombinant human growth hormone initiation was 5.55 years. The baseline height standard deviation score was-3.01. During the first 2 years, 10 patients received short-acting growth hormone and 10 patients received long-acting growth hormone. The median height standard deviation score increased to-2.20 after 1 year and-1.84 after 2 years, with significant longitudinal improvement over time. The cumulative change in height standard deviation score did not differ significantly between short-acting growth hormone and long-acting growth hormone at year 1 (0.58 vs. 0.71) or year 2 (1.01 vs. 1.30). First-year growth velocity was comparable between groups, whereas the apparent second-year difference was no longer significant after excluding short-acting growth hormone-treated patients who entered puberty and received adjunctive therapy. Among 16 patients with PTPN11 variants, the median cumulative change in height standard deviation score was 1.20 and 56.3% achieved an HtSDS of above-2 standard deviation score at the last follow-up. No diabetes mellitus, malignancy, new cardiovascular events, intracranial hypertension, or slipped capital femoral epiphysis occurred. Insulin-like growth factor-1 standard deviation score elevations were transient. Recombinant human growth hormone therapy was associated with sustained linear growth in children with Noonan syndrome, and short-acting growth hormone and long-acting growth hormone showed broadly comparable short-term efficacy under regular safety monitoring.