VARIABILITY IN THE GROWTH-HORMONE RESPONSE TO GROWTH HORMONE-RELEASING HORMONE ALONE OR COMBINED WITH PYRIDOSTIGMINE IN TYPE-1 DIABETIC-PATIENTS

In man the GH response to GHRH is variable within and between subjects . Pyridostigmine (PD), an acetylcholinesterase inhibitor, has been sho wn to reduce the variability of the GH response to GHRH in normal subj ects. The aim of this study was to assess the existence of either inte r- or intraindividual variability in the GH response to GHRH in type 1 diabetic patients. Moreover, we investigated the effect of PD on such variability in the same patients. Seven (4 females-3 males) nonobese type 1 diabetic patients underwent two experiments performed in consec utive days according to a single-blind protocol: 1) 120 mg oral PD 60 min before iv injection of human (h) GHRH-(1-29) NH2, 100 mug in 2 ml of sterile water; 2) oral placebo 60 m in before iv injection of 100 m ug hGHRH. The two experiments were then repeated, following the same p rocedure, one and two weeks after the start of the study. The GH peaks after GHRH were variable within different subjects but also in the sa me subject on different occasions. However, the mean GH peak levels af ter GHRH in the three tests were not significantly different (14.2+/-3 .5, 15.3+/-3, 16.5+/-6.4 mug/L, respectively), the coefficient of vari ation for each test was 65%, 51.8%, 102.4%, respectively (mean 73.1+/- 15.1 %). The GH response to GHRH was always significantly enhanced by PD administration: the mean GH peak levels in the three tests were 31. 9+/-7.1, 44.8+/-10.4, 49.9+/-13.1 mug/L, respectively, without signifi cant differences between tests. After PD+GHRH the interindividual vari ability in the GH response was still present but significantly lower t han after GHRH alone. The coefficient of variation for each test was 5 8.7%, 61.3%, 69.3%, respectively (mean 63.1+/-3.2%). It can be hypothe sized that PD may reduce the interindividual variability of the GH res ponse to GHRH in the diabetic population by decreasing somatostatin to ne only in diabetic patients with normal-high hypothalamic somatostati n.