THE EFFECT OF LONG-ACTING ANALOG OF LUTEINIZING-HORMONE-RELEASING HORMONE ON GROWTH-HORMONE SECRETORY DYNAMICS IN CHILDREN WITH PRECOCIOUS PUBERTY

Long-acting preparations of LHRH (LHRHa), such as leuprolide acetate, have been shown to selectively and reversibly suppress the clinical and biochemical features of central precocious puberty (CPP). The withdrawal of gonadal sex steroids results in a decline of growth velocity and a decrease in the rate of bone age maturation, with resultant improvement in predicted adult stature. The purpose of this study was to define GH secretory dynamics in children treated with leuprolide acetate. Twelve-hour nocturnal GH studies were performed in five children (four girls and one boy) with CPP before and after 6 months of treatment with leuprolide acetate. Mean GH levels, GH secretory rate, and number of GH secretory episodes were determined. Secretory profiles were analyzed using the Cluster program. Growth velocity, somatomedin-C, and dehydroepiandrosterone sulfate were measured before and after 6 months of therapy. By 6 months of therapy, there was a significant decrease in mean growth velocity from 10.5 +/- 3.3 to 6.7 +/- 1.6 cm/yr. Somatomedin-C levels remained the same at 46.90 +/- 9.51 and 52.5 +/- 12.40 nmol/L. Levels of dehydroepiandrosterone sulfate remained unchanged at 118.6 +/- 71.4 and 139.0 +/- 61.3-mu-mol/L at 0 and 6 months of the study. By 6 months, there was a significant decrease in mean GH levels from 13.6 +/- 5.3 to 6.4 +/- 3.4-mu-g/L (P < 0.05). Total GH levels decreased from 1367.9 +/- 687.3 to 447.0 +/- 186.5 ng/12 h. The number of GH secretory episodes remained the same at 5.4 +/- 1.5 and 4.8 +/- 1.0/12 h at 0 and 6 months of study. Therefore, the decrease in GH that occurs during the withdrawal of gonadal sex steroids with LHRHa in children with CPP is an amplitude-modulated phenomenon, as the number of secretory peaks remains unchanged.