ESPE Abstracts

Objectives: Limited information is available on how very young children with growth hormone deficiency (GHD) respond to growth hormone (GH) replacement. We compared response to 1 year of GH therapy in children aged <2 years and prepubertal children aged ≥2 years.

Methods: The two non-interventional, multicentre studies, NordiNet^® International Outcome Study (IOS) (NCT00960128) and the ANSWER Program (NCT01009905), evaluated the effectiveness of Norditropin^® (somatropin; Novo Nordisk A/S) as prescribed in a real-world clinical setting. Height standard deviation scores (SDS) and target height SDS were based on national standards (NordiNet^® IOS) or the Centers for Disease Control standard.

Results: Baseline characteristics [% or mean (SD)] for patients <2 years (n=506) vs. ≥2 years (n=9810): male: 59.7% vs. 69.3%; age at treatment start (years): 1.11 (0.57) vs. 9.09 (3.40); bone age/chronological age: 0.86 (0.99) vs. 0.81 (0.18); height SDS: –2.55 (1.77) vs. –2.39 (1.01); target height SDS: –0.20 (0.98) vs. –0.57 (1.02); GH peak (ng/mL): 4.07 (4.78) vs. 5.45 (4.68); IGF–I SDS: –1.34 (1.07) vs. –1.71 (1.59); birth weight (g): 3033.3 (680.7) vs. 3032.3 (697.1); birth length (cm): 48.3 (3.8) vs. 48.9 (3.9); GH dose (mg/kg/day): 0.035 (0.014) vs. 0.037 (0.011). Isolated GHD was less common in patients aged <2 years (54.6%) vs. ≥2 years (91.4%). Numbers of additional pituitary deficiencies were as follows (<2 years vs. ≥2 years): one: 24.11% vs. 5.92%; two: 12.85% vs. 1.34%; ≥3: 8.50% vs. 1.32%. After 1 year's treatment, all growth-related measurements improved in both groups: [mean (SD)] values: height SDS: –1.17 (1.50) vs. –1.73 (1.00); IGF–I SDS: 0.76 (1.42) vs. 0.41 (1.61); height SDS change from baseline: 1.44 (1.22) vs. 0.67 (0.49). After 1 year mean GH dose (mg/kg/day) was 0.035 (0.011) vs. 0.038 (0.012); median dose [P10; P90] was 0.034 [0.023; 0.049] vs. 0.036 [0.026; 0.053]. Adverse reactions (considered possibly related to treatment) were reported in 1.78% vs. 1.83%, and serious adverse reactions in 0.79% vs. 0.45% (<2 years vs. ≥2 years, respectively).

Conclusion: Children aged <2 years who required GH replacement had more severe GHD, as indicated by lower mean GH peak levels in stimulation tests versus prepubertal children aged ≥2 years. The prevalence of multiple pituitary deficiency was higher in younger children; therefore, clinicians must test them for additional pituitary deficiencies. Severe GHDs should be fully investigated and treated early, which is demonstrated by greater height gain after 1 year's treatment.