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Growth Hormone (GH) Dosing during Catch-Up Growth Guided by Individual Responsiveness Decreases Growth Response Variability in Prepubertal Children with GH Deficiency or Idiopathic Short Stature

Göteborg Pediatric Growth Research Center (B.K., J.D., K.A.-W.), Department of Pediatrics, Institute of Clinical Science, The Sahlgrenska Academy at University of Gothenburg, SE-416 85 Göteborg, Sweden; Department of Clinical Science, Pediatrics (B.K.), Umeå University, SE-901 85 Umeå, Sweden; Department of Pediatrics (A.S.A., N.-O.N.), The Central County Hospital of Halmstad, SE-30185 Halmstad, Sweden; Department of Women’s and Children’s Health (J.G., M.H., T.T.), Uppsala University, SE-75185 Uppsala, Sweden; and Department of Clinical Sciences (S.A.I., J.S.), University Hospital Malmö, Lund University, SE-20502 Malmö, Sweden

Address all correspondence and requests for reprints to: Kerstin Albertsson Wikland, GP-GRC/Växthuset, The Queen Silvia Children’s Hospital, SE-416 85 Göteborg, Sweden. E-mail: kerstin.albertsson-wikland{at}pediat.gu.se.

Context: Weight-based GH dosing results in a wide variation in growth response in children with GH deficiency (GHD) or idiopathic short stature (ISS).

Objective: The hypothesis tested was whether individualized GH doses, based on variation in GH responsiveness estimated by a prediction model, reduced variability in growth response around a set height target compared with a standardized weight-based dose.

Setting: A total of 153 short prepubertal children diagnosed with isolated GHD or ISS (n = 43) and at least 1 SD score (SDS) below midparental height SDS (MPH_SDS) were included in this 2-yr multicenter study.

Intervention: The children were randomized to either a standard (43 µg/kg · d) or individualized (17–100 µg/kg · d) GH dose.

Main Outcome Measure: We measured the deviation of height_SDS from individual MPH_SDS (diffMPH_SDS). The primary endpoint was the difference in the range of diffMPH_SDS between the two groups.

Results: The diffMPH_SDS range was reduced by 32% in the individualized-dose group relative to the standard-dose group (P < 0.003), whereas the mean diffMPH_SDS was equal: –0.42 ± 0.46 and –0.48 ± 0.67, respectively. Gain in height_SDS 0–2 yr was equal for the GH-deficient and ISS groups: 1.31 ± 0.47 and 1.36 ± 0.47, respectively, when ISS was classified on the basis of maximum GH peak on the arginine-insulin tolerance test or 24-h profile.

Conclusion: Individualized GH doses during catch-up growth significantly reduce the proportion of unexpectedly good and poor responders around a predefined individual growth target and result in equal growth responses in children with GHD and ISS.