PRETREATMENT WITH SOMATOSTATIN ANALOG SMS 201-995 POTENTIATES GROWTH-HORMONE (GH) RESPONSIVENESS TO GH-RELEASING FACTOR IN SHORT CHILDREN

Previous studies in children have shown inconsistent, poorly reproducible GH responses to exogenous GH-releasing factor (GRF), with wide individual variability. In the present study, we tested the hypothesis that prior administration of the long-acting somatostatin analog, SMS 201-995 (SMS), will enhance GH responsiveness to a subsequent GRF challenge. Two study protocols were employed in 37 children with short stature [M = 31, F = 6, ages 11.8 +/- 1.6 yr (mean +/- SEM), height -2.25 +/- 0.55 SDS (SD scores)]. In both studies, each subject served as his/her own control. In the first study, which was designed to determine optimal SMS dose and regimen, SMS, in doses ranging from 0.8-2.2 mug/kg sc, was randomly administered or omitted at 0800 h after an overnight fast, and a GRF bolus (50 mug, iv) was given 4 h later. In the second study, we employed a protocol identical to study 1 except for the use of standard doses of SMS (1 mug/kg, sc) and GRF (1 mug/kg, iv) and an additional 1-h delay of the GRF injection. Plasma GH levels were measured every 20 min from 0800 h until 2 h after the GRF injection in both studies. In study 1 (n = 12; M = 10, F = 2), SMS significantly suppressed spontaneous GH secretion (expressed as the mean +/- SEM GH AUC during the 4-h SMS-GRF interval, AUC 1: 2.2 +/- 0.4 vs. 6.2 +/- 0.9 mug/L.h; P < 0.001), GH responsiveness to GRF (GH AUC during the 2 h after the GRF injection, AUC 2: 41.5 +/- 7.8 vs. 85.0 +/- 13.5 mug/L.h; P < 0.001), and the GH peak response (17.4 +/- 3.1 vs. 36.0 +/- 6.2 mug/L; P < 0.001), compared to control tests. In contrast, in study 2 (n = 25; M = 21, F = 4), whereas spontaneous GH secretion was still suppressed during the 5-h SMS-GRF interval (AUC 103.8 +/- 0.4 vs. 7.4 +/- 1.1 mug/L.h, P < 0.001), both the GH peak response (56.7 +/- 5.5 vs. 30.5 +/- 3.0 mug/L; P < 0.0001) and the GH AUC (AUC 2:103.7 +/- 10.3 vs. 77.5 +/- 6.8 mug/L.h; P < 0.05) after GRF administration significantly augmented by pretreatment with SMS, compared to control tests. Taken together these results indicate that a priming SMS dose of 1 mug/kg has a significant permissive effect on GH responsiveness to exogenous GRF administered 5 h later. The combined SMS-GRF test may facilitate the discrimination between normal short children and those with truly diminished GH secretion.