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

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 stimuli3 micrograms/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.We aimed to verify the GH response to GHRH (1 microgram/kg i.v.) combined with pyridostigmine (PD, 120 mg p.o.) or arginine (ARG, 0.5 g/kg i.v.), in 26 hypopituitaric patients (GHD), in 11 obese women (OB), in 8 women with Cushing's syndrome (CS), and in 72 control subjects (NS).IGF-l levels in GHD were lower than those in OB (p0.01) and in CS (p0.01) which, in turn, were lower to those in NS (p0.02). In NS, the GH peak responses to GHRH + PD and GHRH + ARG were similar and the minimum normal GH peak was 16.5 micrograms/L. GHD had GH responses similar, lower than those in NS (p0.01) and always below the normal limit. However, only 12/20 and 8/14 had peaks3 micrograms/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 (p0.01) and higher (p0.01) than those in NS and GHD, respectively. Six out of 11 OB had GH peaks below the normal limits but nobody3 micrograms/L. In CS the GH response to GHRH + PD was lower than that to GHRH + ARG (p0.01); both these responses were lower than those in NS (p0.01) and even in OB (p0.01) but higher than those in GHD (p0.01). All and 7/8 CS had GH peaks lower than normal limits after PD + GHRH and ARG + GHRH, respectively while 6/8 showed GH peak3 micrograms/L after PD + GHRH but only 1 after ARG + GHRH.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.