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,Robert Gut,John A Germak

doi:10.1186/1687-9856-2012-15

Abstract

BackgroundNoonan 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.MethodsThe 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.ResultsThe 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).ConclusionsGH 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 registrationClinicalTrials.gov NCT01009905

Highlights

Noonan syndrome (NS), a genetic disorder first described by Noonan and Ehmke in 1963 [1], is characterized by phenotypic features including facial dysmorphology, cardiovascular anomalies, and short stature [2]
The success of Growth hormone (GH) therapy for patients with NS may be influenced by the genetic causes of the disorder, genetic mutations have not been identified in all patients with NS [9]
Dosing was determined by the treating physician. Both GH-naïve and non-naïve patients are included in the American Norditropin Studies: Web-Enabled Research (ANSWER) Program registry, data from only GH-treatment-naïve patients with NS were included in the current analysis

Summary

Results

Baseline demographics and patient disposition The ANSWER Program registry contained information for 120 children (90 boys and 30 girls) with NS. Mean (SD) HSDS increased from –2.65 (0.73) at baseline to –1.32 (1.11) after 4 years of treatment (Figure 1A). There was a significantly greater ΔHSDS from baseline for the younger age group versus the older age group after 1 and 2 years of treatment; no significant differences were observed among girls at either time point, which may reflect the lower number of female patients (Table 2). The number of children with post-baseline IGF-1 SDS data was limited, mean (SD) IGF-1 SDS increased from a value of –2.96 (1.55) at baseline (n = 73) to –1.35 (2.31) after 1 year of treatment (n = 17), A. Mean (SD) weight increased from baseline following 4 years of treatment, whereas body mass index (BMI) remained stable (Figure 3).

Conclusions

Introduction

Objective and methods

Discussion

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