Growth hormone (GH) treatment in short normal children: absence of influence of time of injection and resistance to GH autofeedback.

Forty prepubertal subjects (25 boys and 15 girls) with idiopathic short stature, aged 3.8-14.6 yr, were randomly allocated to receive sc injections of recombinant human GH (hGH) 6 days/week at a dose of 3 IU (1.25 mg)/m2.day either in the morning or in the evening. After 6 months of therapy, each subject was switched over to the other schedule of injection. After 12 months, treatment was stopped, and the subjects were followed for 6 months. For the whole group, regardless of the time of injection, height velocity (centimeters per yr) was 4.3 +/- 0.9 before hGH treatment, 8.3 +/- 1.9 during the first 6 months of treatment, and 6.9 +/- 1.6 during the last 6 months of treatment. Thirty-three of 38 subjects (87%) who completed 12 months of therapy presented an increase in height velocity greater than 2 cm/yr. Two patients (5%) developed antibodies to hGH and were among the nonresponders. There was no significant difference in growth response according to the schedule of injections. GH-releasing hormone (GHRH) testing was performed before and after 6 and 12 months of hGH therapy. When the last hGH injection was performed 12 h before the GHRH test, there was a 36% decrease in the maximum GH response (P less than 0.01) and a 33% decrease (P less than 0.01) in the GH secretory area compared to those before therapy. When the last hGH injection was performed 24 h or more before the GHRH test, no significant differences were observed. Insulin-like growth factor-I levels were not significantly different when measured 12 or 24 h after hGH. During the 6 months after discontinuation of hGH therapy, catch-down growth was observed in 44% of the subjects. We conclude that the schedule of injection does not influence the growth response, which wanes after 6 months; this waning effect is not related to declining insulin-like growth factor-I levels or GH autofeedback, suggesting a peripheral mechanism. Likewise, the catch-down phenomenon after hGH is discontinued is not related to a persistent diminution of pituitary responsiveness to GHRH.