<b><i>Introduction:</i></b> Few data exist on long-term growth hormone (GH) treatment in patients with Noonan syndrome (NS). <b><i>Objective:</i></b> To evaluate the effectiveness and safety of GH treatment in NS in clinical practice. <b><i>Methods:</i></b> Height gain, near-adult height (NAH), and safety were assessed in 2 complementary non-interventional studies: NordiNet® IOS and ANSWER. The safety analysis included 412 patients, and the effectiveness analysis included 84 GH-treated patients (male, <i>n</i> = 67) with ≥4 years’ height standard deviation score (HSDS) data. HSDS was determined using national reference (NR) and NS-specific (NSS) data. <b><i>Results:</i></b> The mean (SD) baseline age was 8.38 (3.57) years; HSDS, −2.76 (1.03); GH dose, 41.6 (11.1) µg/kg/day. The mean (SD) HSDS increase from baseline (ΔHSDS) was 0.49 (0.37) (first year), 0.79 (0.58) (second year), and 1.01 (0.60) (third year) (NR). The mean (SD) HSDS at year 3 was −1.66 (1.00) (NR; 1.06 [1.12] [NSS]). Twenty-four patients achieved NAH. The mean (SD) NAH SDS (NR) was −1.51 (0.60) (154.90 [3.21] cm) in females and −1.79 (1.09) (165.61 [7.19] cm) in males; 70.8% (17/24) had NAH SDS ≥ −2. Adverse drug reactions and GH-unrelated serious adverse events (<i>n</i> = 34) were reported in 22/412 (5.3%) patients. Four neoplasms and 3 cases of scoliosis were reported; no cardiovascular adverse events occurred. <b><i>Conclusions:</i></b> GH-treated children with NS achieved substantial height gain during the first 3 years of follow-up. Overall, 24 patients achieved NAH, with 70.8% having NAH SDS ≥ –2. There was no evidence to support a higher prevalence of neoplasm, or cardiac or other comorbidities.
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