Objectives: The recently updated clinical practice guidelines for Turner syndrome (TS) recommend a growth hormone (GH) dose of 4550 μg/kg/day, increasing to 68 μg/kg/day in case adult height potential is substantially compromised (1). Real-world data on the modifiable factors impacting near-adult height in GH-treated TS patients are limited, but short-term responsiveness to GH has been suggested as one factor (2). We, therefore, analysed the impact of GH dose on short-term height outcomes in a large cohort of paediatric patients with TS.
Methods: Two complementary, non-interventional, multicentre studies, NordiNet® IOS (NCT00960128) and the ANSWER Program (NCT01009905), evaluated the long-term effectiveness and safety of Norditropin® (somatropin; Novo Nordisk A/S, Denmark) as prescribed by treating physicians in a real-world clinical setting. Data from 1125 TS patients were included in the analysis. Changes in height standard deviation score (ΔHSDS) and association with GH dose were evaluated using a repeated measures mixed model, adjusting for factors previously shown to impact height gain: age at treatment start as well as baseline and target HSDS.
Results: Baseline characteristics [mean (SD)]: age at treatment start (years), 8.60 (3.83); height (cm), 114.76 (19.75); HSDS, −2.61 (0.92); target HSDS, −0.18 (0.97); insulin-like growth factor-I standard deviation score, −0.84 (1.48); bone age/chronological age ratio, 0.87 (0.15). Mean GH dose (μg/kg/day) was 45.21 (11.00) at baseline, and 46.52 (9.70) and 45.83 (9.77) for years 1 and 2, respectively. Mean increase in height from baseline (cm) was 8.46 (2.53) at year 1 and 15.12 (3.66) at year 2. Statistical analysis showed that a GH dose of <50 μg/kg/day was associated with a significantly lower increase in HSDS versus a dose of ≥50 μg/kg/day (P=0.0407). Mean estimated ΔHSDS (SD) were: patients receiving <50 μg/kg/day: 0.51 (0.12) at year 1 and 0.78 (0.11) at year 2; patients receiving ≥50 μg/kg/day: 0.59 (0.11) at year 1 and 0.85 (0.13) at year 2.
Conclusions: These data suggest that higher GH doses are associated with greater short-term height gain in patients with TS. The results support the importance of dose optimisation in this patient population. Although a safety evaluation was outside the scope of this analysis, no new safety signals were identified in this patient cohort.
Reference: 1. Gravholt CH et al. Eur J Endocrinol 2017;177:G1G70.
2. Ranke MB et al. Pediatr Res 2007;61:105110.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology