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Children with growth hormone insensitivity syndrome (GHIS) who receive insulin-like growth factor 1 (IGF-1) treatment and enter puberty with inadequate height gain are unlikely to reach adult height within the normal range. Final height standard deviation score (SDS) in most treated children is ≤-5. Combining IGF-1 with gonadotrophin-releasing hormone analogue (GnRHa) therapy may help to improve their final height. Three patients on IGF-1 treatment, two with primary GHI and one with secondary GHI, were started on GnRHa therapy at the onset of puberty. Their ages ranged from 6.4 years to 12.9 years at the start of IGF-1 therapy (120 μg/kg twice daily by subcutaneous injection). Gains in height/bone age SDSs under GnRHa therapy ranged from 0 to 0.9. Growth velocity on GnRHa therapy ranged from 4 cm/year to 4.8 cm/year. Bone maturation (measured as change in bone age divided by change in chronological age, ΔBA/ΔCA) decreased after the start of GnRHa therapy. Predicted adult height (PAH) improved in two patients and was maintained in one. Bone mineral density showed gradual improvement from baseline. Treatment with GnRHa resulted in a gain in PAH. Final height results will provide the definite answer on the effectiveness of this combined treatment.

Effect of GnRH analogue on height potential in patients with severe growth hormone insensitivity syndrome treated with IGF-I