rGHRH(1-29)NH2

Objective: 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. Design: 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 One patient was non-compliant and was withdrawn prior to 3 months of therapy.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. Measurements: Overnight GH profiles were analysed using the Pulsar program. Results: 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. Conclusions: 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.

We have treated eight pre-pubertal children with partial GH insufficiency with continuous subcutaneous infusions of GHRH(1-29)NH2 at a dose of 60 ng/kg/min for periods of up to 1 year. In five children treated for 1 year, mean growth velocity increased from 4.6 cm/year (range 4.4-5.2) to 7.0 cm/year (5.7-8.7) (P = 0.04). Three children treated for 3-6 months showed similar height velocity increases. A return to pretreatment growth rates was seen after cessation of treatment in all children. Twenty-four-hour GH profiles performed at intervals of 3 months showed sustained augmentation of pulsatile GH secretion without evidence of desensitization. The presence of pulsatile GH secretion during continuous GHRH administration provides strong evidence in man for the role of somatostatin in determining GH pulse frequency. The ability of the pituitary to respond to a supramaximal bolus of GHRH remained constant during the treatment. Continuous administration of GHRH(1-29)NH2 will become a practicable treatment when formulated into a sustained release or depot preparation. We have shown this to be an effective therapy for some short, slowly growing children. Further studies are required to establish the optimal dosage regimen.

More than 80% of children with growth hormone deficiency (GHD) respond with a rise in growth hormone levels when given 1 microgram/kg body weight of growth hormone-releasing hormone (GHRH) in an i.v. bolus. We conducted a study to determine whether the failure of the remaining 20% to respond to GHRH is due to a pituitary deficiency or a secondary effect associated with chronically understimulated somatotrophs. We administered GHRH to "prime" 16 short-statured children (> 2 SD) presenting delayed growth (< 4 cm/year), who had not responded initially when given a single dose of GHRH. Priming consisted of administering GHRH (1-29) NH2 (5 micrograms/kg body weight, s.c.) for six consecutive days. Plasma GH response was studied again after an i.v. injection of 1 microgram/kg body weight of GHRH (1-29) NH2 on the seventh morning. On the basis of these results we were able to separate our patients into two groups: a) responders to priming (n = 8), whose GH responses to pharmacological and acute GHRH tests were < 10 ng/ml, with a 12-hour sleep secretion < 3 ng/ml/min. Priming increased the plasma GH response to acute GHRH in all the children in this group (6.0 +/- 2.1 ng/ml to 18.0 +/- 5.4 ng/ml; p < 0.001); b) non-responders to priming (n = 8), whose GH responses to pharmacological and acute GHRH tests were also < 10 ng/ml, with 12-hour sleep secretion < 3 ng/ml/min, but in whom priming with GH did not increase the plasma GH response (5.5 +/- 2.8 ng/ml to 6.2 +/- 2.9 ng/ml; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)