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High Serum Levels of Growth Hormone (GH) and Insulin-Like Growth Factor-I (IGF-I) during High-Dose GH Treatment in Short Children Born Small for Gestational Age

Department of Pediatrics (M.v.D., A.H.-K.), Division of Endocrinology, Sophia Children’s Hospital, Erasmus Medical Center, 3015 GJ Rotterdam, The Netherlands; Department of Epidemiology and Biostatistics (P.M.), Erasmus Medical Center, 3015 GD Rotterdam, The Netherlands; Juliana Children’s Hospital (M.H.), 2566 ER The Hague, The Netherlands; Rijnstate Hospital (J.M.), 6815 AD Arnhem, The Netherlands; University Medical Center (K.N.), St. Radboud, 6525 GA Nijmegen, The Netherlands; Beatrix Children’s Hospital (R.J.O.), 9713 GZ Groningen, The Netherlands; Canisius-Wilhelmina Hospital (C.R.-W.), 6532 SZ Nijmegen, The Netherlands; Free University Medical Center (P.V.), 1081 HV Amsterdam, The Netherlands; Catharina Hospital (J.W.), 5623 EJ Eindhoven, The Netherlands; and University Medical Center (J.S.-B.), 2333 ZA Leiden, The Netherlands

Address all correspondence and requests for reprints to: Marije van Dijk, Erasmus University Medical Center, Sophia Children’s Hospital, Department of Pediatrics, Division of Endocrinology, sk-0152, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands. E-mail: m.vandijk.1{at}erasmusmc.nl.

Context: Epidemiological studies have indicated that high serum levels of GH and IGF-I are associated with long-term risks.

Objective: The objective of the study was to evaluate the changes in serum levels of GH during overnight profiles, IGF-I, and IGF binding protein 3 (IGFBP-3) in short small for gestational age (SGA) children during GH treatment with two doses.

Patients: Thirty-six prepubertal short SGA children were the subjects of this study.

Intervention: Subjects received 1 (group A) or 2 (group B) mg GH/m²·d.

Main Outcome Measures: At baseline and after 6 months of GH treatment, overnight GH profiles were performed, and serum IGF-I and IGFBP-3 levels were measured.

Results: After 6 months, group B had significantly higher GH levels during the profile (mean, maximum, and area under the curve above zero line) than group A (P < 0.009). In group B, maximum GH levels increased from 43.9–161 mU/liter (P < 0.0002), and in group A, from 57.2–104 mU/liter (P = 0.002). During the profile (i.e. 12 h per day), children of group B had mean GH levels of 64.4 vs. 34.8 mU/liter in group A (P = 0.001). The IGF-I and IGF-I to IGFBP-3 ratio SD scores increased significantly in both groups, but were higher in group B than A [1.5 vs. 0.2 (P = 0.002) and 1.4 vs. 0.3 (P = 0.007), respectively]. In group B, 74% of the children had IGF-I levels in the highest quintile during GH treatment compared with 19% in group A.

Conclusion: Our study shows that high-dose GH treatment in short SGA children results in high serum GH and IGF-I levels in most children. We recommend monitoring IGF-I levels during GH therapy to ensure that these remain within the normal range.

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