REPEATED ADMINISTRATION OF GROWTH HORMONE-RELEASING HORMONE WITH OR WITHOUT PREVIOUS ADMINISTRATION OF PYRIDOSTIGMINE IN INSULIN-DEPENDENT DIABETES-MELLITUS

In insulin dependent diabetes mellitus (IDDM) either elevated growth h ormone (GH) levels or abnormal responses to specific as well as unspec ific stimuli have been reported. As hyperglycemia is known to blunt GH response to various stimuli, a normal GH response to GHRH in presence of hyperglycemia should also be considered inappropriate. To investig ate the mechanism underlying this inappropriate GH response, in 9 pati ents with IDDM, selected for normal GH response to GHRH, we studied th e GH response to two consecutive GHRH boluses (1 mu g/kg), the second of which preceeded 30 min before by pyridostigmine (120 mg p.o.). Seve n age matched normal volunteers were evaluated as control group. Basal plasma glucose and serum GH levels were significantly higher in patie nts with IDDM than in normal subjects (184.4 +/- 9.6 vs 86.2 +/- 4.4 m g/dl, p < 0.01 and 2.4 +/- 1.0 vs 1.0 +/- 0.4 mu g/l, p < 0.01 respect ively). Both in normal subjects and in patients with IDDM the GH respo nse to the second consecutive GHRH administration was lower than that of the first GHRH bolus (Delta AUC: 82.5 +/- 28.3 vs 401.1 +/- 131.2 m u g/l/h, p < 0.05 and 77.2 +/- 30.4 vs 336.8 +/- 60.0, p < 0.02, respe ctively). Pyridostigmine was able to restore the blunted GH responsive ness to the second GHRH administration in both groups, but this respon se was found higher in normal than in diabetic subjects (Delta AUC: 12 50.8 +/- 136.2 vs 527.5 +/- 147.6, p < 0.01). Since the GH-releasing e ffect of PD is likely to be mediated by the inhibition of hypothalamic somatostatin release, our results suggest that there is also an impai red somatostatin tone in hyperglycemic type 1 diabetic patients with n ormal GH response to GHRH.