Treatment with GHRH(1‐29)NH2 in children with idiopathic short stature induces a sustained increase in growth velocity

Abstract

Therapy with GHRH in patients with mild GH insufficiency appears to be more effective than in those with severe insufficiency. We, therefore, studied the clinical response of children with idiopathic short stature to treatment with GHRH(1-29)NH2 (GHRHa) for a period of 12 months. Eighteen short pre-pubertal children (aged 4.3-11.0 years, 17 male) with idiopathic short stature (height < 3rd centile, peak GH to provocative testing > 20 mU/l) were recruited to receive GHRHa 20 micrograms/kg by twice daily s.c. injection for one year. One patient was non-compliant and was withdrawn prior to 3 months of therapy. Pretreatment height velocity was calculated for 12 months and subjects were measured 3-monthly during therapy. Overnight GH profiles and s.c. GHRH tests (20 micrograms/kg) were performed at 0, 3, 6 and 12 months of therapy. In addition, an i.v. GHRH test (1 microgram/kg) was performed at the start and after 1 month of therapy. Overnight GH profiles were analysed using the Pulsar program. Mean (SD) height velocity (HV) increased from 4.8(0.9)cm/year pre-treatment to 7.2(1.6)cm/year after 12 months of therapy (P = 0.001). The children growing slowly (HV < 25th centile) before treatment had a greater growth response than those growing normally (HV > or = 25th centile) before treatment. Final height prediction increased by a mean (SD) of 3.4(2.6)cm. Overnight GH levels and GH responses to GHRH testing fell during the 12 months of therapy. Fasting blood glucose and insulin levels increased during therapy, as did IGF-I. Cessation of GHRHa was followed by catch-down growth during the first 3 months off therapy: mean (SD) HV 3.89(1.82)cm/year (P < 0.04), although the HV after 6 months (4.9(1.0))cm/year) and 12 months (4.4(1.0)cm/year) was not different from pretreatment values. Short-term therapy with twice-daily s.c. injection of GHRHa (20 micrograms/kg) promoted linear growth in short children who were not GH-insufficient. The improved height velocity was sustained throughout the 12 months of treatment, followed by catch-down growth, and returned to pretreatment velocity after cessation of therapy.