GH response to GHRH combined with pyridostigmine or arginine in different conditions of low somatotrope secretion in adulthood: Obesity and Cushing's syndrome in comparison with hypopituitarism

Background. Diagnosing GH deficiency in adults is difficult due to the age-related variations of GH/IGF-I axis and the influence of nutrition. Nowadays, GH replacement is allowed for patients with GH peak to provocative stimuli <3 μg/L. Somatotrope insufficiency is present in hypopituitarism but also in obesity and hypercortisolism. However, to evaluate GH insufficiency in adults is difficult due to variations of GH and IGF-I levels as function of age and nutrition status. Methods. We aimed to verify the GH response to GHRH (1 μg/kg iv) combined with pyridostigmine (PD, 120 mg po) or arginine (ARG, 0.5 g/kg iv), in 26 hypopituitaric patients (GHD), in 11 obese women (OB), in 8 women with Cushing's syndrome (CS), and in 72 control subjects (NS). Results. IGF-I levels in GHD were lower than those in OB (p<0.01) and in CS (p< 0.01) which, in turn, were lower to those in NS (p<0.02). In NS, the GH peak responses to GHRH+PD and GHRH+ARG were similar and the minimum normal GH peak was 16.5 μg/L. GHD had GH responses similar, lower than those in NS (p<0.01) and always below the normal limit. However, only 12/20 and 8/14 had peaks <3 μg/L; conventionally, below this limit severe GH deficiency is shown and rhGH replacement is allowed. In OB, the GH responses to GHRH+PD and GHRH+ARG were similar, lower (p<0.01) and higher (p<0.01) than those in NS and GHD, respectively. Six out of 11 OB had GH peaks below the normal limits but nobody <3 μg/L. In CS, the GH response to GHRH+PD was lower than that to GHRH+ARG (p<0.01); both these responses were lower than those in NS (p<0.01) and even in OB (p<0.01) but higher than those in GHD (p<0.01). All and 7/8 CS had GH peaks lower than normal limits after PD+GHRH and ARG+GHRH, respectively while 6/8 showed GH peak <3 μg/L after PD+GHRH but only 1 after ARG+GHRH. Conclusions. Present data demonstrate that the maximal somatotrope secretory capacity is reduced in OB and even more in CS. From a diagnostic point of view, PD+GHRH and ARG+GHRH tests distinguish OB from severe GHD. As hypercortisolism impairs the activity of cholinesterase inhibitors, only ARG+GHRH, but not PD+GHRH is a reliable test to explore the maximal somatotrope secretory capacity in CS. Notably, even with the ARG+GHRH test, in CS the maximal somatotrope secretory capacity is sometimes so reduced as to overlap with that of severe GHD.