Growth hormone treatment in Noonan syndrome: The National Cooperative Growth Study experience,☆☆,,★★,

https://doi.org/10.1016/S0022-3476(96)70005-7Get rights and content

Abstract

We evaluated the response to growth hormone (GH) therapy in 150 children (97 boys) with Noonan syndrome (NS) by analyzing growth data from children with NS who were enrolled in the National Cooperative Growth Study and compared those data with National Cooperative Growth Study growth data from children with idiopathic growth hormone deficiency (IGHD) and Turner syndrome (TS). Children with NS were significantly shorter than those with IGHD and TS. The annualized growth rates for years 1, 2, 3, and 4 of therapy in patients with NS who were naive to previous GH therapy were significantly greater than baseline. Their growth rates for years 1, 2, 3, and 4 were intermediate between those in children with IGHD and TS and were significantly different from both. A significant improvement occurred in height SD scores for those 42 children with NS who have been monitored for at least 4 years of GH therapy. Three of six boys with NS for whom adult height data were available exceeded their pretreatment predicted heights. (J PEDIATR 1996;128:S18-21)

Section snippets

Subjects

The methods of subject enrollment and data collection have been previously described.14 The NCGS includes 150 prepubertal and pubertal children (97 boys) with NS who had not been treated with GH before enrollment (data collection: June 1986 through February 1995). The diagnosis of NS was made by the treating physician. The enrollment forms included reports of congenital heart disease in 42% of these children and dysmorphic features in 76% of them. Relevant concomitant medications were

RESULTS

The mean height SDS at enrollment was -3.5 standardized to normal growth data from the National Center for Health Statistics15 and -1.35 standardized to the NS growth data of Ranke et al.6 The stimulated peak GH levels were less than 10 μg/L in 45% of the children, but their response to GH therapy was no different from that in children with stimulated peak GH levels greater than 10 μg/L.

Baseline characteristics of patients with NS, IGHD, and TS are shown in Table I. The ages at enrollment were

DISCUSSION

The patients with NS in the NCGS were short even by NS standards, because their height SDS was -1.35 according to the NS growth curves. As a group they were older and shorter and had a greater BA deficit than children in the NCGS with IGHD. Forty-two percent of these patients were reported to have congenital heart disease. In light of the known prevalence of cardiac lesions in NS, this occurrence represents a selection bias or was underreported. Among all the patients with NS in the NCGS, no

References (16)

There are more references available in the full text version of this article.

Cited by (75)

  • Gonadal function in Noonan syndrome

    2022, Annales d'Endocrinologie
    Citation Excerpt :

    Puberty is usually delayed of about two years for both gender in NS in comparison with the general population. In NS girls, the mean age at pubertal onset is between 13 and 14 years [5,6] and the mean age at menarche is around 14.5 years [7,8]. In NS boys, the mean age at pubertal onset is between 13.5 and 14.5 years [6,8–11] and men report first shave at a mean age of 17 years [7].

  • Management of growth failure and other endocrine aspects in patients with Noonan syndrome across Europe: A sub-analysis of a European clinical practice survey

    2022, European Journal of Medical Genetics
    Citation Excerpt :

    In view of the mechanisms underlying short stature in patients with NS, the usefulness of GH stimulation tests is disputable. Indeed, while there have been reports on GHD (Cotterill et al., 1996; Romano et al., 1996) or neurosecretory dysfunction (Ahmed et al., 1991; Noordam et al., 2001b; Tanaka et al., 1992), patients with NS (notably those with PTPN11 mutations) usually display normal or slightly increased GH levels associated with low serum IGF1 levels, suggesting GH insensitivity (Binder et al., 2005; Limal et al., 2006). GH insensitivity, as well as abnormal chondrocyte differentiation, both involving hyperactivation of the RAS/MAPK signalling pathway, were confirmed in vivo in transgenic mice expressing a NS-associated Ptpn11 allele (De Rocca Serra-Nedelec et al., 2012; Tajan et al., 2018).

  • Foreword

    2019, Noonan Syndrome: Characteristics and Interventions
  • Foreword

    2019, Noonan Syndrome: Characteristics and Interventions
  • Cardiac manifestations in noonan syndrome: Effects of growth hormone therapy

    2019, Noonan Syndrome: Characteristics and Interventions
View all citing articles on Scopus

From the Department of Pediatrics, New York Medical College, Valhalla, the Department of Pediatrics, State University of New York at Stony Brook, and the Department of Medical Affairs, Genentech, Inc., South San Francisco, California

☆☆

aSandra L. Blethen, MD, is a principal investigator on research contracts for Genentech, Inc., and is an advisor to the National Cooperative Growth Study.

bKen Dana is employed by Genentech, Inc.

★★

Reprint requests: Alicia A. Romano, MD, Department of Pediatrics, New York Medical College, Valhalla, NY 10595.

0022-3476/96/$5.00 + 0 9/0/72347

View full text