Noonan syndrome and Turner syndrome patients respond similarly to 4 years’ growth-hormone therapy: longitudinal analysis of growth-hormone-naïve patients enrolled in the NordiNet® International Outcome Study and the ANSWER Program
Henrik T. Christesen ; John A. Germak ; Primoz Kotnik ; Birgitte Tønnes Pedersen ; Judith L. Ross ; Peter A. Lee
Penn State College of Medicine, The Milton S. Hershey Medical Center, 500 University Dr., MC-H085, Hershey 17033-0850, PA, USA Hans Christian Andersen Children’s Hospital, Odense University Hospital, Odense, Denmark DuPont Hospital for Children, Wilmington, DE, USA Novo Nordisk Inc, Princeton, NJ, USA Department of Pediatric Endocrinology, University Children’s Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia Epidemiology, Novo Nordisk A/S, Søborg, Denmark
Published In 2015, received in 2015-04-24, accepted in 2015-08-05
【 摘 要 】
Turner syndrome (TS) and Noonan syndrome (NS) are distinct syndromes associated with short stature and other similar phenotypic features. We compared the responses to growth hormone (GH) therapy of TS and NS patients enrolled in the NordiNet® International Outcome Study (IOS) or the American Norditropin Studies: Web-Enabled Research (ANSWER) Program, which collect information on GH therapy in clinical practice.
Repeated-measures regression analysis was performed on change in height standard deviation score (HSDS) and target-height-corrected HSDS, based on national normal references and treatment-naïve disease-specific references. Models were adjusted for baseline age and HSDS, and average GH dose. The study population was paediatric patients with TS and NS in the NordiNet® IOS and ANSWER Program. Longitudinal growth responses over 4 years were evaluated.
In 30 NS patients (24 males; baseline age 8.39 ± 3.45 years) and 294 TS patients (7.81 ± 3.22 years), 4-year adjusted ΔHSDS were +1.14 ± 0.13 and +1.03 ± 0.04, respectively (national references). Based on untreated, disease-specific references, 4-year adjusted ΔHSDS for NS and TS were +1.48 ± 0.10 and +1.79 ± 0.04. The analyses showed a significant increase in HSDS over time for both NS and TS (P < 0.0001). ΔHSDS in NS was higher with younger baseline age; ΔHSDS in TS was higher for patients with younger baseline age and higher GH dose.
NS and TS patients responded well and similarly over 4 years of GH treatment.
2015 Lee et al.
【 预 览 】
【 图 表 】
【 参考文献 】
Chacko E, Graber E, Regelmann MO, Wallach E, Costin G, Rapaport R. Update on Turner and Noonan syndromes. Endocrinol Metab Clin North Am. 2012; 41:713-34.
Chacko EM, Rapaport R. Short stature and its treatment in Turner and Noonan syndromes. Curr Opin Endocrinol Diabetes Obes. 2012; 19:40-6.
Baxter L, Bryant J, Cave CB, Milne R. Recombinant growth hormone for children and adolescents with Turner syndrome. Cochrane Database Syst Rev. 2007:CD003887.
Bondy CA. Care of girls and women with Turner syndrome: a guideline of the Turner Syndrome Study Group. J Clin Endocrinol Metab. 2007; 92:10-25.
Romano AA, Allanson JE, Dahlgren J, Gelb BD, Hall B, Pierpont ME et al.. Noonan syndrome: clinical features, diagnosis, and management guidelines. Pediatrics. 2010; 126:746-59.
Noonan JA, Kappelgaard AM. The efficacy and safety of growth hormone therapy in children with noonan syndrome: a review of the evidence. Horm Res Paediatr. 2015; 83:157-66.
Ranke MB, Heidemann P, Knupfer C, Enders H, Schmaltz AA, Bierich JR. Noonan syndrome: growth and clinical manifestations in 144 cases. Eur J Pediatr. 1988; 148:220-7.
Lee PA, Ross J, Germak JA, Gut R. Effect of 4 years of growth hormone therapy in children with Noonan syndrome in the American Norditropin Studies: Web-Enabled Research (ANSWER) Program® registry. Int J Pediatr Endocrinol. 2012; 2012:15. BioMed Central Full Text
Richmond E, Rogol AD. Current indications for growth hormone therapy for children and adolescents. Endocr Dev. 2010; 18:92-108.
Blum WF, Ross JL, Zimmermann AG, Quigley CA, Child CJ, Kalifa G et al.. GH treatment to final height produces similar height gains in patients with SHOX deficiency and Turner syndrome: results of a multicenter trial. J Clin Endocrinol Metab. 2013; 98:E1383-E1392.
Lee PA, Germak J, Gut R, Khutoryansky N, Ross J. Identification of factors associated with good response to growth hormone therapy in children with short stature: results from the ANSWER Program®. Int J Pediatr Endocrinol. 2011; 2011:6. BioMed Central Full Text
Pasquino AM, Passeri F, Municchi G, Segni M, Pucarelli I, Larizza D et al.. Final height in Turner syndrome patients treated with growth hormone. Horm Res. 1996; 46:269-72.
Raaijmakers R, Noordam C, Karagiannis G, Gregory JW, Hertel NT, Sipila I et al.. Response to growth hormone treatment and final height in Noonan syndrome in a large cohort of patients in the KIGS database. J Pediatr Endocrinol Metab. 2008; 21:267-73.
Rosenfeld RG, Frane J, Attie KM, Brasel JA, Burstein S, Cara JF et al.. Six-year results of a randomized, prospective trial of human growth hormone and oxandrolone in Turner syndrome. J Pediatr. 1992; 121:49-55.
Ranke MB. Noonan syndrome: growth to growth hormone - the experience of observational studies. Horm Res. 2009; 72 Suppl 2:36-40.
Romano AA, Dana K, Bakker B, Davis DA, Hunold JJ, Jacobs J et al.. Growth response, near-adult height, and patterns of growth and puberty in patients with noonan syndrome treated with growth hormone. J Clin Endocrinol Metab. 2009; 94:2338-44.
Höybye C, Sävendahl L, Christesen HT, Lee P, Pedersen BT, Schlumpf M et al.. The NordiNet® International Outcome Study and NovoNet® ANSWER Program®: rationale, design, and methodology of two international pharmacoepidemiological registry-based studies monitoring long-term clinical and safety outcomes of growth hormone therapy (Norditropin®). Clin Epidemiol. 2013; 5:119-27.
Brabant G, von zur Mühlen A, Wüster C, Ranke MB, Kratzsch J, Kiess W et al.. Serum insulin-like growth factor I reference values for an automated chemiluminescence immunoassay system: results from a multicenter study. Horm Res. 2003; 60:53-60.
Ranke MB, Stubbe P, Majewski F, Bierich JR. Spontaneous growth in Turner's syndrome. Acta Paediatr Scand Suppl. 1988; 343:22-30.
Cabrol S, Saab C, Gourmelen M, Raux-Demay MC, Le Bouc Y. Turner syndrome: spontaneous growth of stature, weight increase and accelerated bone maturation. Arch Pediatr. 1996; 3:313-8.
Rongen-Westerlaken C, Corel L, van den Broeck J, Massa G, Karlberg J, Albertsson-Wikland K et al.. Reference values for height, height velocity and weight in Turner's syndrome. Swedish Study Group for GH treatment. Acta Paediatrica. 1997; 86:937-42.
Otten BJ, Noordam C. Growth in Noonan syndrome. Horm Res. 2009; 72 Suppl 2:31-5.
Binder G, Grathwol S, Von LK, Blumenstock G, Kaulitz R, Freiberg C, et al. Health and quality of life in adults with Noonan syndrome. J Pediatr. 2012;161:501–5.
Dahlgren J. GH therapy in Noonan syndrome: review of final height data. Horm Res. 2009; 72 Suppl 2:46-8.
Osio D, Dahlgren J, Wikland KA, Westphal O. Improved final height with long-term growth hormone treatment in Noonan syndrome. Acta Paediatrica. 2005; 94:1232-7.
MacFarlane CE, Brown DC, Johnston LB, Patton MA, Dunger DB, Savage MO et al.. Growth hormone therapy and growth in children with Noonan's syndrome: results of 3 years' follow-up. J Clin Endocrinol Metab. 2001; 86:1953-6.
Choi JH, Lee BH, Jung CW, Kim YM, Jin HY, Kim JM et al.. Response to growth hormone therapy in children with Noonan syndrome: correlation with or without PTPN11 gene mutation. Horm Res Paediatr. 2012; 77:388-93.
De Rocca Serra-Nédélec A, Edouard T, Treguer K, Tajan M, Araki T, Dance M et al.. Noonan syndrome-causing SHP2 mutants inhibit insulin-like growth factor 1 release via growth hormone-induced ERK hyperactivation, which contributes to short stature. Proc Natl Acad Sci U S A. 2012; 109:4257-62.
Noordam C, Peer PG, Francois I, De Schepper J, van den Burgt I, Otten BJ. Long-term GH treatment improves adult height in children with Noonan syndrome with and without mutations in protein tyrosine phosphatase, non-receptor-type 11. Eur J Endocrinol. 2008; 159:203-8.
Ferreira LV, Souza SA, Arnhold IJ, Mendonca BB, Jorge AA. PTPN11 (protein tyrosine phosphatase, nonreceptor type 11) mutations and response to growth hormone therapy in children with Noonan syndrome. J Clin Endocrinol Metab. 2005; 90:5156-60.
Bertelloni S, Baroncelli GI, Dati E, Ghione S, Baldinotti F, Toschi B et al.. IGF-I generation test in prepubertal children with Noonan syndrome due to mutations in the PTPN11 gene. Hormones (Athens). 2013; 12:86-92.
Ross J, Lee PA, Gut R, Germak J. Impact of age and duration of growth hormone therapy in children with Turner syndrome. Horm Res Paediatr. 2011; 76:392-9.
Ross JL, Quigley CA, Cao D, Feuillan P, Kowal K, Chipman JJ et al.. Growth hormone plus childhood low-dose estrogen in Turner's syndrome. N Engl J Med. 2011; 364:1230-42.
Ranke MB, Lindberg A, Brosz M, Kaspers S, Loftus J, Wollmann H et al.. Accurate long-term prediction of height during the first four years of growth hormone treatment in prepubertal children with growth hormone deficiency or Turner Syndrome. Horm Res Paediatr. 2012; 78:8-17.
Bettendorf M, Inta IM, Doerr HG, Hauffa BP, Mehls O, Ranke MB. Height gain in Ullrich-Turner syndrome after early and late growth hormone treatment start: results from a large retrospective German study and potential basis for an individualized treatment approach. Horm Res Paediatr. 2013; 80:356-62.