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Long-term efficacy of recombinant human growth hormone therapy in short-statured patients with Noonan syndrome.

Jeong I, Kang E, Cho JH, Kim GH, Lee BH, Choi JH, Yoo HW - Ann Pediatr Endocrinol Metab (2016)

Bottom Line: Although this study included a relatively small number of patients, long-term rhGH therapy in NS patients was safe and effective at improving height, growth velocity, and serum IGF-1 levels, in accordance with previous studies.However, the meticulous monitoring of potential adverse events is still needed because of high dose of rhGH and preexisting hyperactivity of RAS-MAPK pathway.Patients with PTPN11 mutations demonstrated a decreased response to rhGH therapy compared to those without mutations.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.

ABSTRACT

Purpose: Noonan syndrome (NS) is characterized by short stature, heart anomalies, developmental delays, dysmorphic features, cryptorchidism, and coagulation defects. Several studies reported the short-term effects of recombinant human growth hormone (rhGH) treatment on the improvement of height. This study was performed to evaluate the long-term efficacy of rhGH in children with NS in Korea.

Methods: This study included 15 prepubertal NS children who received rhGH subcutaneously at a dose of 50-75 µg/kg/day for 6 days a week for at least >3 years. Preand posttreatment data, such as height, weight, bone age, insulin-like growth factor 1 (IGF-1), and IGF binding protein 3 (IGFBP-3) levels, were collected every 6 months.

Results: Chronologic age and bone age at the start of treatment were 7.97±1.81 and 5.09±2.12 years, respectively. Height standard deviation score (SDS) was increased from -2.64±0.64 to -1.54±1.24 years after 3 years (P<0.001). Serum IGF-1 SDS levels were elevated from -1.28±1.03 to -0.10±0.94 (P<0.001). Height SDS was more increased in subjects without PTPN11 mutations compared to those with mutations after 3 years (P=0.012). However, the other parameters, including bone age, IGF-1 SDS, and IGFBP-3 SDS, were not significantly different between patients with and without PTPN11 mutations.

Conclusion: Although this study included a relatively small number of patients, long-term rhGH therapy in NS patients was safe and effective at improving height, growth velocity, and serum IGF-1 levels, in accordance with previous studies. However, the meticulous monitoring of potential adverse events is still needed because of high dose of rhGH and preexisting hyperactivity of RAS-MAPK pathway. Patients with PTPN11 mutations demonstrated a decreased response to rhGH therapy compared to those without mutations.

No MeSH data available.


Related in: MedlinePlus

Sequential changes of height SDS (A), GV (B), and IGF-1 SDS (C) during rhGH treatment in patients with Noonan syndrome with or without PTPN11 mutations. Mann-Whitney U-test was used to compare the response to rhGH therapy according to genotypes. P-values less than 0.05 were considered to be statistically significant. SDS, standard deviation score; GV, growth velocity; IGF-1, insulin-like growth factor 1; rhGH, recombinant human growth hormone.
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Figure 1: Sequential changes of height SDS (A), GV (B), and IGF-1 SDS (C) during rhGH treatment in patients with Noonan syndrome with or without PTPN11 mutations. Mann-Whitney U-test was used to compare the response to rhGH therapy according to genotypes. P-values less than 0.05 were considered to be statistically significant. SDS, standard deviation score; GV, growth velocity; IGF-1, insulin-like growth factor 1; rhGH, recombinant human growth hormone.

Mentions: The influence of genotype was analyzed by comparing the growth parameters at the start of treatment and 1 year, 2 years, and 3 years after treatment. IGF-1 SDS was significantly different between the group with PTPN11 mutations and the group without PTPN11 mutations at the start of treatment (P=0.036). The other baseline data, including bone age, height SDS, GV, and serum IGFBP-3 levels, were not significantly different between the 2 groups (P=0.607, P=0.181, P=0.818, and P=0.224, respectively) (Fig. 1). Responses to treatment over 3 years, represented by changes in bone age, GV, serum IGF-1 SDS, and IGFBP-3 SDS, were not significantly different among children with and without mutations in PTPN11 (P=0.755, P=0.864, P=0.113, and P=0.145, respectively). However, height SDS was significantly increased in patients without PTPN11 mutations compared to those with mutations (P=0.012) (Fig. 1).


Long-term efficacy of recombinant human growth hormone therapy in short-statured patients with Noonan syndrome.

Jeong I, Kang E, Cho JH, Kim GH, Lee BH, Choi JH, Yoo HW - Ann Pediatr Endocrinol Metab (2016)

Sequential changes of height SDS (A), GV (B), and IGF-1 SDS (C) during rhGH treatment in patients with Noonan syndrome with or without PTPN11 mutations. Mann-Whitney U-test was used to compare the response to rhGH therapy according to genotypes. P-values less than 0.05 were considered to be statistically significant. SDS, standard deviation score; GV, growth velocity; IGF-1, insulin-like growth factor 1; rhGH, recombinant human growth hormone.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835558&req=5

Figure 1: Sequential changes of height SDS (A), GV (B), and IGF-1 SDS (C) during rhGH treatment in patients with Noonan syndrome with or without PTPN11 mutations. Mann-Whitney U-test was used to compare the response to rhGH therapy according to genotypes. P-values less than 0.05 were considered to be statistically significant. SDS, standard deviation score; GV, growth velocity; IGF-1, insulin-like growth factor 1; rhGH, recombinant human growth hormone.
Mentions: The influence of genotype was analyzed by comparing the growth parameters at the start of treatment and 1 year, 2 years, and 3 years after treatment. IGF-1 SDS was significantly different between the group with PTPN11 mutations and the group without PTPN11 mutations at the start of treatment (P=0.036). The other baseline data, including bone age, height SDS, GV, and serum IGFBP-3 levels, were not significantly different between the 2 groups (P=0.607, P=0.181, P=0.818, and P=0.224, respectively) (Fig. 1). Responses to treatment over 3 years, represented by changes in bone age, GV, serum IGF-1 SDS, and IGFBP-3 SDS, were not significantly different among children with and without mutations in PTPN11 (P=0.755, P=0.864, P=0.113, and P=0.145, respectively). However, height SDS was significantly increased in patients without PTPN11 mutations compared to those with mutations (P=0.012) (Fig. 1).

Bottom Line: Although this study included a relatively small number of patients, long-term rhGH therapy in NS patients was safe and effective at improving height, growth velocity, and serum IGF-1 levels, in accordance with previous studies.However, the meticulous monitoring of potential adverse events is still needed because of high dose of rhGH and preexisting hyperactivity of RAS-MAPK pathway.Patients with PTPN11 mutations demonstrated a decreased response to rhGH therapy compared to those without mutations.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.

ABSTRACT

Purpose: Noonan syndrome (NS) is characterized by short stature, heart anomalies, developmental delays, dysmorphic features, cryptorchidism, and coagulation defects. Several studies reported the short-term effects of recombinant human growth hormone (rhGH) treatment on the improvement of height. This study was performed to evaluate the long-term efficacy of rhGH in children with NS in Korea.

Methods: This study included 15 prepubertal NS children who received rhGH subcutaneously at a dose of 50-75 µg/kg/day for 6 days a week for at least >3 years. Preand posttreatment data, such as height, weight, bone age, insulin-like growth factor 1 (IGF-1), and IGF binding protein 3 (IGFBP-3) levels, were collected every 6 months.

Results: Chronologic age and bone age at the start of treatment were 7.97±1.81 and 5.09±2.12 years, respectively. Height standard deviation score (SDS) was increased from -2.64±0.64 to -1.54±1.24 years after 3 years (P<0.001). Serum IGF-1 SDS levels were elevated from -1.28±1.03 to -0.10±0.94 (P<0.001). Height SDS was more increased in subjects without PTPN11 mutations compared to those with mutations after 3 years (P=0.012). However, the other parameters, including bone age, IGF-1 SDS, and IGFBP-3 SDS, were not significantly different between patients with and without PTPN11 mutations.

Conclusion: Although this study included a relatively small number of patients, long-term rhGH therapy in NS patients was safe and effective at improving height, growth velocity, and serum IGF-1 levels, in accordance with previous studies. However, the meticulous monitoring of potential adverse events is still needed because of high dose of rhGH and preexisting hyperactivity of RAS-MAPK pathway. Patients with PTPN11 mutations demonstrated a decreased response to rhGH therapy compared to those without mutations.

No MeSH data available.


Related in: MedlinePlus