This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ranke, M. B. Articles by Price, D. A. Search for Related Content PubMed PubMed Citation Articles by Ranke, M. B. Articles by Price, D. A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Genetics Home Reference Hazardous Substances DB OXANDROLONE Medline Plus Health Information Turner Syndrome

Prediction of Long-Term Response to Recombinant Human Growth Hormone in Turner Syndrome: Development and Validation of Mathematical Models

Pediatric Endocrinology Section, University Children’s Hospital (M.B.R.), D-72076 Tuebingen, Germany; Pharmacia & Upjohn, Inc. (A.L., P.W.), SE-11287 Stockholm, Sweden; Service de Pédiatrie, Endocrinologie et Diabétologie Infantiles, Université Claude Bernard, Hôpital Debrousse (P.C.), F-69322 Lyon, France; Department of Pediatrics, University of Auckland (W.C.), 92019 Auckland, New Zealand; Goteborg Pediatric Growth Research Center, Department of Pediatrics, Queen Silvia’s Children’s Hospital (K.A.-W.), SE-41685 Gothenburg, Sweden; and Department of Pediatrics, St. Mary’s Hospital (D.A.P.), Manchester, M27 1HA United Kingdom

Address all correspondence and requests for reprints to: Prof. Michael B. Ranke, Pediatric Endocrinology Section, University Children’s Hospital, Hoppe-Seyler Strasse 1, D-72076 Tuebingen, Germany.

It has become common practice to apply GH treatment in short Turner syndrome patients with the objective of promoting growth. The variability in response and the high costs of this treatment demand the individualization and optimization of therapy. Based on 686 prepubertal Turner patients from the Kabi International Growth Study (KIGS; Pharmacia & Upjohn, Inc. International Growth Database), we undertook a multiple regression analysis of height velocity (centimeters per yr) by using various parameters of potential relevance. Derived prediction models for the first 4 yr of GH treatment were validated with 76 additional KIGS patients and 81 patients from Tuebingen, Germany. Among the 6 predictors identified, the most influential variable for first year growth response was the natural log (ln) of the weekly GH dose. The first year growth response was also correlated with age and distance between height and target height (SD score; both negative) and body weight SD, number of GH injections per week, and oxandrolone treatment given additionally (positive). The first year model explains 46% of the variability, with 1 SD of 1.26 cm. For the second to fourth years, 5 predictors were identified: height velocity during previous years, weekly GH dose (ln), weight SD, oxandrolone therapy (all positive), and age (negative). These models explained 32%, 29%, and 30% of the variability, respectively, with SD scores of 1.1, 1.0, and 1.0 cm, respectively. When the models were applied to the other cohorts, no significant difference was noted between observed and predicted responses. Although the parameters used in our models do not entirely explain the variability in the growth response in Turner syndrome, the parameters themselves were clinically relevant to our present understanding and proved to be of high precision. Some of the tested markers, such as karyotype, do not contribute to the growth response. These variables make the models practical and suitable for planning beneficial and cost-effective therapy.

This article has been cited by other articles:

				B. Raz, M. Janner, V. Petkovic, D. Lochmatter, A. Eble, M. T. Dattani, P. C. Hindmarsh, C. E. Fluck, and P. E. Mullis Influence of Growth Hormone (GH) Receptor Deletion of Exon 3 and Full-Length Isoforms on GH Response and Final Height in Patients with Severe GH Deficiency J. Clin. Endocrinol. Metab., March 1, 2008; 93(3): 974 - 980. [Abstract] [Full Text] [PDF]

				B. Bakker, J. Frane, H. Anhalt, B. Lippe, and R. G. Rosenfeld Height Velocity Targets from the National Cooperative Growth Study for First-Year Growth Hormone Responses in Short Children J. Clin. Endocrinol. Metab., February 1, 2008; 93(2): 352 - 357. [Abstract] [Full Text] [PDF]

				M. L. Davenport, B. J. Crowe, S. H. Travers, K. Rubin, J. L. Ross, P. Y. Fechner, D. F. Gunther, C. Liu, M. E. Geffner, K. Thrailkill, et al. Growth Hormone Treatment of Early Growth Failure in Toddlers with Turner Syndrome: A Randomized, Controlled, Multicenter Trial J. Clin. Endocrinol. Metab., September 1, 2007; 92(9): 3406 - 3416. [Abstract] [Full Text] [PDF]

				C. A. Bondy and for The Turner Syndrome Consensus Study Group Care of Girls and Women with Turner Syndrome: A Guideline of the Turner Syndrome Study Group J. Clin. Endocrinol. Metab., January 1, 2007; 92(1): 10 - 25. [Abstract] [Full Text] [PDF]

				M D C Donaldson, E J Gault, K W Tan, and D B Dunger Optimising management in Turner syndrome: from infancy to adult transfer Arch. Dis. Child., June 1, 2006; 91(6): 513 - 520. [Abstract] [Full Text] [PDF]

				G. Binder, F. Baur, R. Schweizer, and M. B. Ranke The d3-Growth Hormone (GH) Receptor Polymorphism Is Associated with Increased Responsiveness to GH in Turner Syndrome and Short Small-for-Gestational-Age Children J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 659 - 664. [Abstract] [Full Text] [PDF]

				L. Soriano-Guillen, J. Coste, E. Ecosse, J. Leger, M. Tauber, S. Cabrol, M. Nicolino, R. Brauner, the StaTur Study Group, J.-L. Chaussain, et al. Adult Height and Pubertal Growth in Turner Syndrome after Treatment with Recombinant Growth Hormone J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5197 - 5204. [Abstract] [Full Text] [PDF]

				J.-C. Carel Growth Hormone in Turner Syndrome: Twenty Years after, What Can We Tell our Patients? J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3793 - 3794. [Full Text] [PDF]

				H. G. Doerr, M. Bettendorf, B. P. Hauffa, O. Mehls, C.-J. Partsch, E. Said, S. Sander, H.-P. Schwarz, N. Stahnke, H. Steinkamp, et al. Uterine size in women with Turner syndrome after induction of puberty with estrogens and long-term growth hormone therapy: results of the German IGLU Follow-up Study 2001 Hum. Reprod., May 1, 2005; 20(5): 1418 - 1421. [Abstract] [Full Text] [PDF]

				M. B. Ranke, A. Lindberg, K. Albertsson-Wikland, P. Wilton, D. A. Price, E. O. Reiter, and on behalf of the KIGS International Board Increased Response, But Lower Responsiveness, to Growth Hormone (GH) in Very Young Children (Aged 0-3 Years) with Idiopathic GH Deficiency: Analysis of Data from KIGS J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 1966 - 1971. [Abstract] [Full Text] [PDF]

				M. B. Ranke, A. Lindberg, C. T. Cowell, K. A. Wikland, E. O. Reiter, P. Wilton, and D. A. Price Prediction of Response to Growth Hormone Treatment in Short Children Born Small for Gestational Age: Analysis of Data from KIGS (Pharmacia International Growth Database) J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 125 - 131. [Abstract] [Full Text] [PDF]

				P. Saenger, K. A. Wikland, G. S. Conway, M. Davenport, C. H. Gravholt, R. Hintz, O. Hovatta, M. Hultcrantz, K. Landin-Wilhelmsen, A. Lin, et al. Recommendations for the Diagnosis and Management of Turner Syndrome J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3061 - 3069. [Abstract] [Full Text] [PDF]

				D A PRICE and M B RANKE Growth hormone in Turner syndrome Arch. Dis. Child., June 1, 2001; 84(6): 525m - 525. [Full Text]

				E. O. Reiter, S. L. Blethen, J. Baptista, and L. Price Early Initiation of Growth Hormone Treatment Allows Age-Appropriate Estrogen Use in Turner's Syndrome J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 1936 - 1941. [Abstract] [Full Text]