Chronic Growth Hormone Administration Does Not Suppress Endogenous Growth Hormone Secretion in Patients with Neurosecretory Growth Hormone Dysfunction

Abstract

Short children who respond normally to growth hormone (GH) stimulation, but have a subnormal spontaneous secretion of GH (neurosecretory GH dysfunction, NSD) are treated with exogenous GH which might suppress their endogenous GH secretion. The effect of chronic administration of GH (8–24 months) on plasma GH responses to GHRH, clonidine and spontaneous GH secretion were studied in 17 NSD patients. The diagnosis of NSD was based on a normal GH response to clonidine ( > 10 µg/l) and an integrated concentration of (IC-GH) GH < 3.2 µg/l. The GH dose used in this study was 0.25 IU/kg three times a week in 10 patients and 0.05 IU/kg daily in 7 patients. Insulin-like growth factor I levels (nmol) increased significantly on therapy from 9.3 ± 3.8 to 24.4 ± 22.4 (p < 0.001). The GH response (µg/l) to GHRH was 20.4 ± 5.5 before treatment and 22.4 ± 6.2 on GH. Peak GH after clonidine was 22.4 ± 8.9 and 22.8 ± 8.1, respectively. There was no significant decrease in the number of GH spontaneous peaks (1.8 ± 0.7 vs. 2.0 ± 0.7, respectively) or in the area under the curve. A subcutaneous GH bolus of 0.25 IU/kg in 4 patients resulted in a GH peak of 55–82 µg/l at 3–5 h and a gradual return to basal levels at 15–20 h after GH administration. The first spontaneous GH peak appeared 26–28 h after GH injection, peak amplitude was 10–15 µg/l. Administration of a smaller subcutaneous dose 0.05 IU/kg to 7 patients resulted in a GH peak of 40 ± 10 µg/l at 4–5 h and a gradual return to basal levels at 10–12 h after GH administration. The first spontaneous GH surge was then noted within 4–7 h of GH return to basal levels. The amplitude of the first spontaneous peak was 30.5–13.0 µg/l. In conclusion, GH therapy in NSD patients on either alternate day or daily basis does not inhibit GH secretion. Four to nine h after GH disappearance, GH secretion recovers; GH recovery is dose dependent.