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Insulin Growth Factor-Based Dosing of Growth Hormone Therapy in Children: A Randomized, Controlled Study

Department of Pediatric Endocrinology (P.C.), Mattel Children’s Hospital at University of California, Los Angeles, Los Angeles, California 90095; Department of Pediatrics (A.D.R.), University of Virginia, Charlottesville, Virginia 22908; Medical Department (C.P.H., G.M.B.), Novo Nordisk Inc., Princeton, New Jersey 08540; Scientific Marketing GHT (A.-M.K.), Novo Nordisk A/S, Virum, Denmark DK-2830; and Medical Affairs (R.G.R), Lucile Packard Foundation for Children’s Health, Palo Alto, California 94304

Address all correspondence and requests for reprints to: Pinchas Cohen, M.D., Department of Pediatric Endocrinology, Mattel Children’s Hospital at UCLA, 10833 Le Conte Avenue, MDCC 22-315, Los Angeles, California 90095. E-mail: hassy{at}mednet.ucla.edu.

Context: Weight-based dosing of GH is the standard of care for short children, although IGF-I is thought to be the main mediator of GH actions on growth.

Objective: The objective of the study was to test whether IGF-I levels achieved during GH therapy are determinants of the growth responses to GH treatment.

Design: This was a 2-yr, open-label, randomized, IGF-I concentration-controlled trial. Prepubertal short children [n = 172, mean age 7.53 yr, mean height SD score (HT-SDS) –2.64] with low IGF-I levels (mean IGF-I SDS –3.56) were randomized to receive one of two GH dose-titration arms in which GH dosage was titrated to achieve an IGF-I SDS at the mean [IGF_(low) group, n = 70] or the upper limit of the normal range [+2 SDS, IGF_(high) group, n = 68] or to a comparison group of conventional GH dose of 40 µg/kg/d (n = 34).

Setting: The study was conducted in a multicenter, outpatient setting.

Primary Outcome Measure: Change in HT-SDS over 2 yr was measured.

Results: One hundred forty-seven patients completed the trial. Target IGF-I levels were achieved in the dose-titration arms within 6–9 months. The changes in HT-SDS were +1.0, +1.1, and +1.6 for conventional, IGF_(low), and IGF_(high), respectively, with IGF_(high) showing significantly greater linear growth response (P < 0.001, compared with the other two groups). The IGF_(high) arm required higher doses (>2.5 times) than the IGF_(low) arm, and these GH doses were highly variable (20–346 µg/kg/d). Multivariate analyses suggested that the rise in the IGF-I SDS significantly impacted height outcome along with the GH dose and the pretreatment peak-stimulated GH level.

Conclusion: IGF-I-based GH dosing is clinically feasible and allows maintaining serum IGF-I concentrations within the desired target range. Titrating the GH dose to achieve higher IGF-I targets results in improved growth responses, although at higher average GH doses.

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