Introduction: Laron syndrome (LS) is a rare autosomal recessive disorder caused by mutations in the growth hormone (GH) receptor gene, resulting in GH resistance and reduced levels of insulin-like growth factor 1 (IGF-1). Patients with LS exhibit severe growth retardation, low IGF-1 levels, elevated basal GH, and poor response to GH stimulation. Recombinant IGF-1 is the only approved treatment and has been shown to improve linear growth. This study evaluates the long-term efficacy and safety of IGF-1 therapy in a large cohort of LS patients treated at King Faisal Specialist Hospital and Research Center (KFSH&RC), Riyadh, Saudi Arabia over 22 years.
Methods: We conducted a retrospective review of medical records for 28 patients with growth hormone insensitivity syndrome (GHIS), including 12 males and 16 females, treated with IGF-1 from 1998 to 2020. Patients were selected based on criteria including age over 2 years, height standard deviation score (SDS) ≤ -2.8, normal or elevated GH secretion (>2.5 ng/ml), IGF-1 levels < 50 ng/ml, and insensitivity to exogenous GH. IGF-1 was administered initially at 40 mcg/kg/dose subcutaneously twice daily, escalating to a maximum of 120 mcg/kg/dose as tolerated. Dosage was adjusted to minimize hypoglycemia risk, with blood glucose monitored frequently during hospitalization. In addition, molecular genetic results were reviewed for each patient in the cohort.
Results: IGF-1 treatment significantly increased height velocity from a baseline of 3.4 cm/year to 6.5 cm/year in the first year (mean difference of 3.1 cm/year, P < 0.0001). In the second year, height velocity remained elevated at 5 cm/year (mean difference of 1.6 cm/year, P = 0.0015). Long-term follow-up over 10 years demonstrated sustained improvements in height velocity compared to baseline, with the most substantial gains occurring within the initial five years. Weight standard deviation scores also showed significant improvement. Age at the start of therapy did not notably affect growth outcomes, though longer treatment durations were associated with greater growth. Ten disease-causing variants in the GHR gene were identified in 24 of the 28 LS patients.
Conclusion: IGF-1 therapy significantly enhanced linear growth in children with Laron syndrome and was generally well tolerated. Although many patients did not reach normal adult height, the growth achieved with IGF-1 treatment was markedly better than expected without therapy. This study underscores the effectiveness of IGF-1 in improving growth outcomes and highlights the need for continued longitudinal studies to optimize treatment strategies and manage potential complications.
The Author(s). Published by S. Karger AG, Basel.