Response to Growth Hormone Treatment and Final Height in Noonan Syndrome in a Large Cohort of Patients in the KIGS Database

Raaijmakers, Renske; Noordam, C.; Karagiannis, Georgios; Gregory, John Welbourn; Hertel, Niels Thomas; Sipilä, Ilkka; Otten, B. J.

doi:10.1515/jpem.2008.21.3.267

Cited by 55 publications

(58 citation statements)

References 18 publications

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“…Intriguingly, these doi: 10.7243/2052-8000-2-1 studies may be distinguished in two classes, depending on the extent of the increase of height SDS they report. Thus Kirk et al, observed a moderate increase in height SDS of 0.8 in 10 patients [22], which is in accordance with a rise of 0.87 in 24 patients reported by Raaijmakers et al, [29]. On the other hand, Osio et al, Noordam et al, and Romano et al, reported better outcomes of GH therapy, with increases in height SDS ranging from 1.3 to 1.7 on a total of 112 patients [26,28,30].…”

Section: Gh Therapy In Nssupporting

confidence: 80%

“…Despite these limitations, it is worthwhile to analyze the different reports which addressed this question [22][23][24][25][26][27][28][29][30][31]. Their data are summarized in Table 1.…”

Section: Gh Therapy In Nsmentioning

confidence: 99%

“…Analyses based on cases of Turner's syndrome or idiopathic short stature assessed this cost as 33,750 to 35,000 US$ per [29]. The mechanism of this waning effect is unknown and further investigations are necessary to address this question and define the factors influencing this effect.…”

Section: Gh Therapy In Nsmentioning

confidence: 99%

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Growth hormone and noonan syndrome: update in dysfunctional signaling aspects and in therapy for short stature

Raynal¹

2014

Horm Stud

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Short stature is a frequent feature of Noonan syndrome (NS), a disease caused by mutations of genes encoding components of the Ras/mitogen-activated protein kinases (MAPK) signalling pathway. To date numerous patients have been treated with growth hormone (GH) in various countries. However this treatment is still controversial, as its efficacy is a matter of debate. The final height gain of GH therapy represents 5 to 10 cm, at best, which is disappointing considering the length and burden of the treatment. The reasons explaining this lack of efficiency are poorly understood and they seemed to involve a waning effect after the first year of GH treatment or acceleration of bone maturation in patients on GH. Moreover, GH therapy raises questions about its safety, especially in subjects with NS who are at risk for cardiac defects and malignancies. Cases of severe adverse effects were described, yet too sporadically to conclude that they were certainly caused by GH therapy. Novels insights in understanding the dysfunction of GH-dependent processes in NS were recently reported and this manuscript aims at reviewing the latest advances. Clinical data suggested that growth retardation could be caused by a partial postreceptor resistance to GH, an impaired sensitivity to GH which could also explain the modest efficiency of GH therapy in NS patients. Similar observations were also obtained in a NS mouse model harboring a mutation in the gene encoding the tyrosine phosphatase Shp2. In the mouse, the mechanism of GH resistance is thought to involve upregulation by mutated Shp2 of GH-induced Ras/MAPK, a signaling pathway which seemed to play a negative regulatory role in the production of GH mediators involved in bone growth. Despite these recent finding, the underlying mechanisms of growth retardation and GH therapy in NS remain to be further explored in order to improve treatment for short stature.

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Section: Gh Therapy In Nssupporting

confidence: 80%

“…Despite these limitations, it is worthwhile to analyze the different reports which addressed this question [22][23][24][25][26][27][28][29][30][31]. Their data are summarized in Table 1.…”

Section: Gh Therapy In Nsmentioning

confidence: 99%

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Growth hormone and noonan syndrome: update in dysfunctional signaling aspects and in therapy for short stature

Raynal¹

2014

Horm Stud

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“…As a whole, current data suggest that the overall increase in height SDS with GH therapy in Noonan syndrome ranges from 0.8 to 1.7 [12,16,30,33], which represents a final height gain of 5 to 10 cm. At first sight, this may seem to be a small gain; however, an increase of 5 to 10 cm may allow a large subset of patients to reach normal adult height.…”

Section: Endocrine Journal Advance Publicationmentioning

confidence: 72%

“…The response to GH therapy in NS can be affected by a number of factors, such as dose of rhGH and type of genetic mutation involved. Moreover, results of long-term GH treatment of short stature due to Noonan syndrome demonstrate a significant improvement in adult height [12].…”

mentioning

confidence: 97%

Efficacy and safety of two doses of Norditropin<sup>®</sup> (somatropin) in short stature due to Noonan syndrome: a 2-year randomized, double-blind, multicenter trial in Japanese patients

et al. 2018

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Abstract. This randomized double-blind multicenter trial (NCT01927861) evaluated the growth-promoting effect and safety of Norditropin ® (NN220; somatropin) in Japanese children with short stature due to Noonan syndrome. Prepubertal children aged 3-<11 years (boys) or 3-<10 years (girls) with Noonan syndrome were randomized to receive GH 0.033 mg/kg/day (n = 25, mean age 6.57 years, 11 females) or 0.066 mg/kg/day (n = 26, mean age 6.06 years, eight females) for 104 weeks. Change in height standard deviation score (HSDS) from baseline was analyzed based on an ANCOVA model. Baseline HSDS was -3.24. Estimated change in HSDS [95% CI] after 104 weeks' treatment was 0.84 [0.66, 1.02] and 1.47 [1.29, 1.64] for the lower and higher doses, respectively; estimated mean difference 0.63 [0.38, 0.88], p < 0.0001. Rates and patterns of adverse events (AEs) were similar between groups. Most were mild and reported as unlikely to be related to Norditropin ® . There were no withdrawals due to AEs. Insulin-like growth factor-I SDS increased from -1.71 to -0.64 (0.033 mg/kg/day) and to 0.63 (0.066 mg/kg/day). HbA 1c increased slightly (0.033 mg/kg/day: +0.14%; 0.066 mg/kg/day: +0.13%); glucose profiles were almost unchanged; insulin profiles increased in both groups in the oral glucose tolerance test. There were no clinically significant abnormal electrocardiogram or echocardiography findings. We conclude that Norditropin ® at doses of 0.033 mg/kg/day or 0.066 mg/kg/day for 104 weeks increases height in Japanese children with short stature due to Noonan syndrome, with a favorable safety profile. The effect was greater with 0.066 mg/kg/day compared with 0.033 mg/kg/day.

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Noonan Syndrome

Allanson

2010

Management of Genetic Syndromes

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Response to Growth Hormone Treatment and Final Height in Noonan Syndrome in a Large Cohort of Patients in the KIGS Database

Cited by 55 publications

References 18 publications

Growth hormone and noonan syndrome: update in dysfunctional signaling aspects and in therapy for short stature

Growth hormone and noonan syndrome: update in dysfunctional signaling aspects and in therapy for short stature

Efficacy and safety of two doses of Norditropin<sup>®</sup> (somatropin) in short stature due to Noonan syndrome: a 2-year randomized, double-blind, multicenter trial in Japanese patients

Noonan Syndrome

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