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 hormone (GH) levels or abnormal responses to specific as well as unspecific 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 investigate the mechanism underlying this inappropriate GH response, in 9 patients with IDDM, selected for normal GH response to GHRH, we studied the GH response to two consecutive GHRH boluses (1 µg/kg), the second of which preceeded 30 min before by pyridostigmine (120 mg p.o.). Seven age matched normal volunteers were evaluated as control group. Basal plasma glucose and serum GH levels were significantly higher in patients with IDDM than in normal subjects (184.4 ± 9.6 vs 86.2 ± 4.4 mg/dl, p < 0.01 and 2.4 ± 1.0 vs 1.0 ± 0.4 mg/l, p <0.01 respectively). Both in normal subjects and in patients with IDDM the GH response to the second consecutive GHRH administration was lower than that of the first GHRH bolus (Δ AUC: 82.5 ± 28.3 vs 401.1 ± 131.2 µg/l/h, p < 0.05 and 77.2 ± 30.4 vs 336.8 ± 60.0, p < 0.02, respectively). Pyridostigmine was able to restore the blunted GH responsiveness to the second GHRH administration in both groups, but this response was found higher in normal than in diabetic subjects (Δ AUC: 1250.8 ± 136.2 vs 527.5 ± 147.6, p < 0.01). Since the GH-releasing effect of PD is likely to be mediated by the inhibition of hypothalamic somatostatin release, our results suggest that there is also an impaired somatostatin tone in hyperglycemic type 1 diabetic patients with normal GH response to GHRH.

Key words

Growth Hormone - Growth Hormone-Releasing Hormone - Insulin Dependent-Diabetes Mellitus