Preservation of Physiological Growth Hormone (GH) Secretion in Idiopathic Short Stature after Recombinant GH Therapy*

Abstract

This study was undertaken to assess the recovery of spontaneous GH secretion 48 h after the cessation of GH therapy in children with idiopathic short stature treated with recombinant DNA-generated human GH (rhGH-M). Eleven prepubertal children with GH responses of 10.0 ng/mL or more after provocation were divided into therapeutic (n = 7) and control (n = 4) groups. GH was sampled every 20 min for 24 h in six treated and three control patients. One treated and one control patient had 12-h overnight studies because of their weight. The sampling studies were carried out before GH therapy was initiated and 48 h after rhGH was discontinued after 12 months of therapy. Three patients in the treated group also underwent a 24-h study at the 6 month time point. The treated group started treatment with rhGH (0.1 mg/kg), given three times a week. The results showed that pre- and posttreatment GH secretory profiles were comparable with respect to the number of peaks, mean concentrations, peak amplitude, and secretory rate. At the 6 month point, the mean GH and peak GH amplitude (n = 3) were greater than the means of the treatment group (n = 7) at the 0 and 12 month points, but the difference was not statistically significant. Somatomedin-C rose in the treated group from 0.42 +/- 0.1 to 1.25 +/- 0.3 U/mL (mean +/- SD; P less than 0.01). In the control group it rose from 0.56 +/- 0.1 to 1.16 +/- 0.8 U/mL (mean +/- SD; P greater than 0.05) because one patient entered puberty in the 12-month period of observation; his somatomedin-C level rose from 0.72 to 2.5 U/mL. We conclude that exogenous GH therapy does not interfere with the maintenance of endogenous pulsatile secretion of GH. These data show that exogenous GH therapy does not interfere with the maintenance of endogenous pulsatile secretion of GH and provide evidence for the resilience of the GH secretory system in the growing child.