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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

Pediatric Endocrinology Section, University Children’s Hospital, Eberhard Karls University (M.B.R.), D-72076 Tuebingen, Germany; Pfizer, Inc. (A.L., P.W.), S-11287 Stockholm, Sweden; Pediatric Growth Research Center, Department of Pediatrics, Queen Silvia Children’s Hospital (K.A.-W.), Sahlgrenska Academy of Goteborg University, S-416 85 Goteborg, Sweden; Department of Pediatrics, St. Mary’s Hospital (D.A.P.), Manchester M27 1HA, United Kingdom; and Baystate Medical Center Children’s Hospital, Tufts University of Medicine (E.O.R.), Springfield, Massachusetts 01106

Address all correspondence and requests for reprints to: Dr. Michael B. Ranke, Pediatric Endocrinology Section, University Children’s Hospital, Hoppe-Seyler Strasse 1, D-72076 Tuebingen, Germany. E-mail: michael.ranke{at}med.uni-tuebingen.de.

In children, GH secretion and sensitivity to GH are influenced by developmental changes. It is not clear whether the response to GH in very young children with GH deficiency (GHD) is the same as that in older, prepubertal children. A cohort of 265 children (180 males and 85 females) with idiopathic GHD from KIGS (Pfizer International Growth Database), with treatment started at less than 3 yr of age (mean age, 1.9 yr; group I) was compared with a cohort of 509 children (331 males and 178 females; group II) with treatment started at 7–8 yr of age (mean age, 7.5 yr). The following differences (P < 0.01) were found (given in mean values) between groups I and II at the start of GH treatment: 9% vs. 5% breech delivery, 38% vs. 14% multiple pituitary hormone deficiency, 4.2 vs. 5.9 ng/ml maximum GH in response to tests, –0.1 vs. –0.8 midparental height (MPH) SD score (SDS), –3.1 vs. –2.5 height SDS, 0.83 vs. 0.66 IU/kg·wk GH dose. After the first year of GH, the results were: 13.3 vs. 8.6 cm/yr height velocity, and 1.7 vs. 0.6 maximum change in height SDS. Using the previously developed growth prediction models for prepubertal children with idiopathic GHD more than 2 yr of age, our analysis revealed differences in the indexes of responsiveness in prediction models (Studentized residuals SDS, 0.7 vs.–0.3) and strikingly higher responsiveness to treatment among the young cohort, but with large scatter. Thus, new prediction models of height velocity (centimeters per year) were derived by means of multiple regression analysis for the young cohort, either involving (model A) or excluding (model B) the GH peak in tests. Model A explained 54% of the total variability with an error SD of 2.1 cm. Height velocity correlated with (parameters in order of importance) age (–), maximum GH (–), GH dose (+), weight SDS (+), height SDS minus MPH SDS (–), and birth weight SDS (+). Model B explained 45% of the total variability with an error SD of 2.3 cm. Height velocity correlated with (parameters in order of importance) age (–), GH dose (+), birth weight SDS (+), height SDS minus MPH SDS (–), and weight SDS (+). The predictors were qualitatively the same as those in the total prepubertal model involving all children more than 2 yr of age, but their quantitative impact in terms of partial contribution and the order of their importance were different for the young cohort. In particular, the partial contribution of the GH dose was higher, suggesting a greater gain in height per GH dose unit in the very young than in the older children. However, the rank order of the GH dose in the new models was lower, which suggests a slightly low sensitivity to GH in toddlers after the phase of severe GH insensitivity during early infancy. The early detection and GH treatment of congenital GHD is advantageous as a cost-effective strategy for achieving greater improvement of absolute height and growth velocity.

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