Short stature in Noonan syndrome: response to growth hormone therapy

Abstract

Background-Growth hormone (GH) has been used to promote growth in both the short and long term in a number of dysmorphic syndromes, including Turner syndrome. As this condition shares many clinical features with Noonan syndrome, it would seem logical to treat the latter group with GH. Aims-To assess the short and long term response to GH therapy in patients with Noonan syndrome. Methods-Analysis of patients with Noonan syndrome in the Pharmacia & Upjohn International Growth Study (this postmarketing database contains data on the majority of patients currently treated with GH in the UK). A questionnaire was also sent to participating clinicians. Results-Data on 66 patients (54 males) were available for study. At the start of GH therapy children were short, compared with both normal and Noonan children. During the first year of GH therapy height velocity increased from a mean of 4.9 to 7.2 cm per year. For patients treated long term with GH, mean height SDS increased from −2.9 pretreatment to −2.6 after one year and −2.3 after five years. Of the 10 patients at near final height, only one had a height above the 3rd centile for normal adults and above the mean for untreated Noonan patients. The mean increment in final height was 3.1 cm (range −1.1 to 6.5 cm). Conclusions-GH therapy in patients withNoonan syndrome will improve height velocity in the short term. Longer-term therapy results in a waning of eVect; initial indications are that final height is not improved substantially in most patients. (Arch Dis Child 2001;84:440-443)

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

“…An additional source of variation between the above studies could be due to different doses of GH used in these studies, even though no significant correlation of given dosage to final height has been found to date [22,26,28]. For example, Osio et al, did not observe a significant difference between two sets of nine patients receiving 0.23 or 0.46 mg of GH per kg and per week [26].…”

“…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].…”

“…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.…”

GH Therapy and first final height data in Noonan‐like syndrome with loose anagen hair (Mazzanti syndrome)

“…These studies have been focused on cohorts including patients with and without molecularly confirmed diagnosis, different genotypes, various age at enrollment, as well as different replacement therapy protocols. Therefore, the analysis of efficacy of GH treatment has provided contradictory results [Kirk et al, 2001;Osio et al, 2005;Otten and Noordam, 2007;Romano et al, 2009;Lee et al, 2012], and a mean height gain ranging between 0.6 and 2 SDS [Dahlgren, 2009].…”

Síndrome de Noonan: do fenótipo à terapêutica com hormônio de crescimento

“…Durante a infância observa-se crescimento paralelo à curva de referência (10) (Figura 2) com escore de desviospadrão de altura em média de -3 (11)(12)(13)(14), observando-se atraso de um a dois anos na idade óssea. A intensidade da baixa estatura não é explicada pela presença de defeitos cardíacos ou pela dificuldade alimentar observada nestes pacientes na infância (15).…”