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Growth Hormone (GH) Treatment in Short Normal Children: Absence of Influence of Time of Injection and Resistance to GH Autofeedback^*

Departments of Pediatrics, Universities of Brussels Belgium
Leuven Belgium
Louvain Belgium
Liege Belgium
Ghent Belgium

Address all correspondence and requests for reprints to: G. Van Vliet, Research Center, Hopital Sainte-Justine, Montreal, Quebec, H3T 1C5 Canada.

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 < 0.01) and a 33% decrease (P < 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.

^* Presented in part at the September 1990 Meeting of the European Society for Pediatric Endocrinology, Vienna, Austria. This work was supported in part by grants from the National Fund for Medical Research, Belgium (no. 3.0047.89 to M.V.-L. and no. 3.4518.85 to G.V.V.) and Eli-Lilly Belgium.

Received January 29, 1991.

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