EFFECTS OF CONTINUOUS GHRH INFUSION ON GH SECRETION IN GH-DEFICIENT PATIENTS WITH HYPOTHALAMIC-PITUITARY ABNORMALITIES

Abstract

To evaluate residual pituitary GH, GH responses to continuous 180-min infusion of increasing doses of GHRH 1-29 followed by iv bolus injection of GHRH were studied in 28 hypopituitary patients, 21 of whom had pituitary abnormalities on MRI. Pituitary hypoplasia, stalk agenesis and ectopic posterior pituitary lobe in 7 patients with isolated GH deficiency (IGHD) and 6 with multiple pituitary hormone deficiencies (group I); isolated pituitary hypoplasia in 8 IGHD (group II); normal pituitary gland morphology in 7 IGHD (group III). Pituitary volume was not significantly different in the groups I and II.The study consisted of 1) 0.9% saline infusion for 30′(50ml/h) from 0830-0900h; 2)GHRH 200 ng/kg body weight/h from 0900-1000h, GHRH 400 ng/kg/h from 1000-1100h and GHRH 600 ng/kg/h from 1100-1200h; 3)iv bolus dose of GHRH (2ug/kg) at 1200h. Blood samples for GH and IGF-1 levels were obtained every 15 min until 1200h and then after 5,10,15,20 and 30′ following GHRH bolus.A slight increase of GH was observed in group I while GHRH infusion significantly increased GH secretion in the groups II and III. Mean GH pulse amplitude as well as mean GH height were significantly lower in group I (1.08±0.35, 3.12±0.94 ng/ml) than in group II (4.74±0.53, 14.89±1.50 ng/ml, p=0.0007) and III (6.78±2.42, 22.93±5.41 ng/ml p=0.0092, p=0.004). A similar trend was also observed for the mean integrated total GH areas over 0-line in the group I (30.24±9.55 ng/ml),II (202.79±33.87 ng/ml, p=0.0003) and III (193.32±27.93 ng/ml, p=0.0004).Spontaneous GH peaks occur during saline infusion in the group III suggesting the presence of two releasable pituitary GH pools. The GH secretion pattern was quite different in groups II (late GH reponse) and III. GH response to the iv bolus dose of GHRH was indicative of pituitary desensitization. Basal IGF-1 was in the normal levels in group III and no variations were detected during GHRH infusion.