Adult and Near-Adult Height in Patients with Severe Insulin-Like Growth Factor-I Deficiency after Long-Term Therapy with Recombinant Human Insulin-Like Growth Factor-I

Abstract

Background: Treatment with recombinant human insulin-like growth factor-I (IGF-I) stimulates linear growth in children with severe IGF-I deficiency (IGFD). Aims: To evaluate the efficacy and safety of treatment with IGF-I in patients with severe IGFD treated until adult or near-adult height. Methods: Twenty-one children with severe IGFD were treated until adult or near-adult height under a predominantly open-label design. All patients were naive to IGF-I. Recombinant human IGF-I was administered subcutaneously in doses between 60 and 120 µg/kg twice daily. Nine patients received additional therapy with gonadotropin- releasing hormone (GnRH) analog for a mean period of 2.9 ± 1.8 years. Results: Mean duration of treatment was 10.0 years. Mean height velocity increased from 3.1 cm/year prior to treatment to 7.4 cm/year during the first year of treatment. Height velocities during the subsequent years were lower, but remained above baseline for up to 12 years. Cumulative mean Δ height SD score at (near) adult height was +2. The observed mean gain in height was 13.4 cm more than had been expected without treatment. The adult height achieved by the patients also treated with GnRH analog was not different from those who received IGF-I therapy alone. There were no new safety signals identified in these patients, a subset of those previously reported. Conclusion: Long-term therapy with IGF-I improves adult height of patients with severe IGFD. Most patients did not bring their heights into the normal adult range.

Effectiveness and Safety of rhIGF-1 Therapy in Children: The European Increlex® Growth Forum Database Experience

“…Only 10 patients have reached adult or near-adult height with a mean of less than -3.4 SDS. In patients with SPIGFD, similar adult or near-adult height was reported by Backeljauw et al [18]. In the EU IGFD Registry, of the 4 patients with a final or near adult height less than -3.4 SDS, 3 had an adult height SDS less than -5.0.…”

“…IGF-1-independent growth-promoting effects of GH, as well as the IGF-1-supporting actions of GH-dependent IGFBP-3 and ALS, are thought to be important for this difference. In a study of long-term follow-up to adult or near-adult height of patients with SPIGFD who received rhIGF-1 treatment, an increase in BMI and body fat measured by dual-energy X-ray absorptiometry was reported [18]. We found that BMI increased, approaching 0 SDS during the first year of treatment.…”

Challenges in the Management of Short Stature

“…The number of patients is low. Long-term therapy with IGF-1 improves the adult height of patients with severe IGF-1 deficiency, although most patients do not experience sufficient catch-up growth to obtain a height in the normal range [48]. Hence, long-term IGF-1 therapy appears to be effective and relatively safe as a replacement therapy in children with SS due to severe IGF-1 deficiency.…”

Past, Present, and Future in the Relationship between Growth Retardation and the IGF System: Excerpts from the Cesar Bergada Lecture Given during the SLEP 2015 Annual Meeting

“…The response to IGF-I treatment of complete GH resistant patients, the majority Laron syndrome, has been reported [13]. From 21 patients enrolled, only 2 boys and 1 girl reached adult height within normal limits.…”