Department of Pediatric Endocrinology, University Children's Hospital, Saarland University Medical Center, Homburg, Germany,
Diabetes and Endocrine Center, Children's Hospital & Clinics of Minnesota, Saint Paul, Minnesota, USA.
Horm Res Paediatr. 2020;93(6):380-395. doi: 10.1159/000512429. Epub 2021 Jan 13.
Few data exist on long-term growth hormone (GH) treatment in patients with Noonan syndrome (NS).
To evaluate the effectiveness and safety of GH treatment in NS in clinical practice.
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, n = 67) with ≥4 years' height standard deviation score (HSDS) data. HSDS was determined using national reference (NR) and NS-specific (NSS) data.
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 (n = 34) were reported in 22/412 (5.3%) patients. Four neoplasms and 3 cases of scoliosis were reported; no cardiovascular adverse events occurred.
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.
关于努南综合征（Noonan syndrome，NS）患者长期生长激素（growth hormone，GH）治疗的数据较少。
评估 GH 治疗 NS 的有效性和安全性。
通过两项非干预性研究 NordiNet®IOS 和 ANSWER 评估身高增长、接近成人身高（near-adult height，NAH）和安全性。安全性分析纳入 412 例患者，有效性分析纳入 84 例 GH 治疗且具有≥4 年身高标准差评分（height standard deviation score，HSDS）数据的患者（男性 67 例）。HSDS 使用国家参考值（national reference，NR）和 NS 特异性参考值（NS-specific reference，NSS）确定。
中位（标准差）基线年龄为 8.38（3.57）岁；HSDS 为-2.76（1.03）；GH 剂量为 41.6（11.1）µg/kg/d。与基线相比，HSDS 平均（标准差）增加（ΔHSDS）为 0.49（0.37）（第 1 年）、0.79（0.58）（第 2 年）和 1.01（0.60）（第 3 年）（NR）。第 3 年的 HSDS 平均（标准差）为-1.66（1.00）（NR；1.06[1.12] [NSS]）。24 例患者达到 NAH。女性 NAH SDS（NR）的平均值（标准差）为-1.51（0.60）（154.90[3.21]cm），男性为-1.79（1.09）（165.61[7.19]cm）；24 例中有 70.8%（17/24）的 NAH SDS≥-2。在 412 例患者中，有 22 例（5.3%）报告了药物相关不良事件和与 GH 无关的严重不良事件（n=34）。报告了 4 例肿瘤和 3 例脊柱侧弯，未发生心血管不良事件。
接受 GH 治疗的 NS 患儿在随访的前 3 年中身高增长显著。总体而言，24 例患者达到 NAH，其中 70.8%的患者 NAH SDS≥-2。无证据表明肿瘤、心脏或其他合并症的患病率更高。
