A Persistent Pattern of Varying Pituitary Responsivity to Exogenous Growth Hormone (GH)-Releasing Hormone in GH-Deficient Children: Evidence Supporting Periodic Somatostatin Secretion*

The pattern and degree of variation in pituitary responsivity to GHRH was examined in four GH-deficient children (two boys and two girls, aged 4 3/12 to 10 4/12 yr). All children were studied before and on multiple (three to six per child) occasions during long term GHRH therapy (1 or 2 micrograms/kg, sc, every 3 h) in an identical fashion. Each study comprised withdrawal of blood for serum GH measurements every 20 min between 2000 and 0800 h. All subjects received GHRH at 2000, 2300, 0200, and 0500 h as well as at 0800, 1100, 1400, and 1700 h throughout the long term treatment period (6-18 months). Although all children had low level (less than 7.0 micrograms/L) pulsatile GH secretion during baseline studies, the maximal peak values occurred at times other than 0500 h. Before GHRH treatment, serum GH levels rose significantly in response to 91% (62 of 68) of the GHRH doses administered. GH pulse amplitudes varied throughout the studies in all children, and this variability persisted despite 1300-3600 consecutive doses in each child. In all 17 study periods the highest serum GH concentration occurred shortly after the 0500 h GHRH dose. The mean peak GH concentration after the 0500 h GHRH dose [18.4 +/- 3.5 (+/- SE) micrograms/L] was significantly higher than those after the 2000 h (5.3 +/- 1.0 micrograms/L; P = 0.0001), 2300 h (7.4 +/- 2.1 micrograms/L; P = 0.0003), and 0200 h (10.9 +/- 2.5 micrograms/L; P = 0.011) doses. These results demonstrate that the responsivity of the pituitary to GHRH varies throughout the night in some GH-deficient children. There appears to be a direct relationship between the time of night and the degree of pituitary responsivity to GHRH. We suggest that this variable responsivity may be due to intermittent hypothalamic somatostatin secretion.