DIFFERENT EFFECTS OF PYRIDOSTIGMINE ON GROWTH-HORMONE (GH) RESPONSE TO GH-RELEASING HORMONE IN ENDOGENOUS AND EXOGENOUS HYPERCORTISOLEMIC PATIENTS

Abstract

1. Somatostatin may play a role in the inhibition of growth hormone (GH) response to GH-releasing hormone (GHRH) in hypercortisolism. To examine this hypothesis we studied the effect of pyridostigmine, a cholinergic agonist that decreases hypothalamic somatostatin, on the GH response to GHRH in 8 controls, in 6 patients with endogenous hypercortisolism (3 with Cushing's disease and 3 with adrenal adenomas) and in 8 patients with exogenous hypercortisolism (lupus erythematosus chronically treated with 20-60 mg/day of prednisone). Each subject received GHRH(1-29)NH2, 100 mu g iv twice, preceded by pyridostigmine (120 mg) of placebo, orally.2. The GH response to GHRH was significantly blunted in all hypercortisolemic patients compared to controls both after placebo (GH peak, 5.8 +/- 1.6 vs 46.2 +/- 15.9 mu g/l, mean +/- SEM) and after pyridostigmine (15.7 +/- 5.6 vs 77.2 +/- 19.8 mu g/l).3. The GH response was absent in endogenous hypercortisolemic patients compared to the exogenous group, both after placebo (2.2 +/- 0.3 vs 8.5 +/- 2.4 mu g/l) and after pyridostigmine (4.9, +/- 2.5 vs 23.8 +/- 8.7 mu g/l). The GH release after GHRH/pyridostigmine for the exogenous group was similar to the response of controls treated with GHRH/placebo.4. These results confirm that the GH response to GHRH is blunted in hypercortisolism, although more pronounced in the endogenous group. Pyridostigmine partially reversed this inhibition in the exogenous group. Therefore, somatostatin may play a role in the inhibition of GHRH-induced GH release in exogenous hypercortisolemic states.