Effect of 4 years of growth hormone therapy in children with Noonan syndrome in the American Norditropin Studies: Web-Enabled Research (ANSWER) Program® registry

Peter A Lee, Judith Ross, John A Germak, Robert Gut, Peter A Lee, Judith Ross, John A Germak, Robert Gut

Abstract

Background: Noonan syndrome (NS) is a genetic disorder characterized by phenotypic features, including facial dysmorphology, cardiovascular anomalies, and short stature. Growth hormone (GH) has been approved by the United States Food and Drug Administration for short stature in children with NS. The objective of this analysis was to assess the height standard deviation score (HSDS) and change in HSDS (ΔHSDS) for up to 4 years (Y4) of GH therapy in children with NS.

Methods: The American Norditropin Studies: Web-Enabled Research (ANSWER) Program®, a US-based registry, collects long-term efficacy and safety information on patients treated with Norditropin® (somatropin rDNA origin, Novo Nordisk A/S) at the discretion of participating physicians. A total of 120 children (90 boys, 30 girls) with NS, naïve to previous GH treatment, were included in this analysis.

Results: The mean (SD) baseline age of subjects (n = 120) was 9.2 (3.8) years. Mean (SD) HSDS increased from -2.65 (0.73) at baseline to -1.32 (1.11) at Y4 (n = 17). Subjects showed continued increase in HSDS from baseline to Y4 without significant differences between genders at Y1 or Y2. The mean (SD) GH dose was 47 (11) mcg/kg/day at baseline and 59 (16) mcg/kg/day at Y4. There was a negative correlation between baseline age and ΔHSDS at Y1 (R = -0.3156; P = 0.0055) and Y2 (R = -0.3394; P = 0.017). ΔHSDS at Y1 was significantly correlated with ΔHSDS at Y2 (n = 37; R = 0.8527, P < 0.0001) and Y3 (n = 20; R = 0.5145; P = 0.0203), but not Y4 (n = 12; R = 0.4066, P = 0.1896).

Conclusions: GH treatment-naïve patients with NS showed continued increases in HSDS during 4 years of treatment with GH with no significant differences between genders up to 2 years. Baseline age was negatively correlated with ΔHSDS at Y1 and Y2. Whether long-term therapy in NS results in continued increase in HSDS to adult height remains to be investigated.

Trial registration: ClinicalTrials.gov NCT01009905.

Figures

Figure 1
Figure 1
Mean HSDS Change at Year 1, Year 2, Year 3, and Year 4: (A) Cross-sectional Data and (B) Longitudinal Data. HSDS, height standard deviation score.
Figure 2
Figure 2
Linear Regression of ΔHSDS at Year 1 and Year 2 on Baseline Age. At both (A) Year 1 (n = 76; correlation = -.3156; P = 0.0055) and (B) Year 2 (n = 49; correlation = -.3394; P = 0.017), there was a significant negative correlation between ΔHSDS and baseline age (ie, ΔHSDS decreased as baseline age increased).
Figure 3
Figure 3
Mean BMI and Weight Change at Year 1, Year 2, Year 3, and Year 4 (Cross-sectional Data). BMI, body mass index/

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