ESPE2018 Poster Presentations Growth & Syndromes P1 (30 abstracts)
aDepartment of Endocrinology, Alder Hey Childrens NHS Foundation Trust, Liverpool, UK. bDepartment of Pediatric Endocrinology, University Childrens Hospital, Saarland University Medical Center, Homburg, Germany. cEpidemiology, Novo Nordisk A/S, Søborg, Denmark. dGlobal Medical Affairs, Novo Nordisk Health Care AG, Zurich, Switzerland. eCincinnati Childrens Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
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.