Adrenocorticotropin and cortisol hyperresponsiveness to hexarelin in patients with Cushing's disease bearing a pituitary microadenoma, but not in those with macroadenoma

We previously reported that in Gushing's disease (CD) the ACTH- and cortiso l (F)-releasing activity of Hexarelin (HEX), a GH secretagogue, is exaggera ted with respect to that in normal subjects and is higher than that of huma n CRH (hGRH), but it is absent in Gushing's syndrome. Our aim was to extend the study about the effects of HEX (2.0 mu g/kg, iv) on ACTH and F secreti on in 21 patients with CD (3 men and 18 women, 16-68 yr old). Based on magn etic resonance imaging, 15 GD patients had pituitary microadenoma, and 6 ha d macroadenoma. The results in CD patients were compared with those in 27 n ormal age-matched controls (NS; 10 men and 17 women, 24-69 yr old). Basal A CTH and F levels in CD were similar in patients with microadenom (mean +/- SEM, 78.3 +/- 7.2 pg/mL, and 237.1 +/- 23.6 mu g/L, respectively) and macro adenoma (57.4 +/- 9.0 pg/mL and 196.4 +/- 20.1 mu g/L, respectively) and we re higher (P < 0.001) than those in NS (11.7 +/- 2.0 pg/mL and 115.3 +/- 6. 7 mu g/L, respectively). In microadenoma CD patients, HEX induced marked AC TH and F increases (Delta peak, mean +/- SEM: 261.2 +/- 77.6 pg/mL, and 226 .1 +/- 87.2 mu g/L, respectively), which were higher (P < 0.04) than those induced by hCRH (45.6 +/- 16.9 pg/mL and 84.6 +/- 25.7 mu g/L, respectively ). Moreover, in microadenoma CD patients, the ACTH and F responses to HEX w ere higher (P < 0.001) than those in NS (18.5 +/- 4.0 pg/mL and 36.1 +/- 6. 8 mu g/L, respectively). In macroadenoma CD patients, HEX induced a slight, but significant increase (P < 0.02) in ACTH and F levels (33.9 +/- 18.0 pg /mL and 89.6 +/- 54.3 mu g/L, respectively), which was not significantly di fferent from that elicited by hCRH (20.0 +/- 7.0 pg/mL and 54.8 +/- 21.3 mu g/L, respectively). In macroadenoma CD patients, the ACTH and F responses to HEX and hCRH were, in turn, similar to those in NS. In conclusion, our findings demonstrate that the ACTH and F hyperresponsive ness to HEX is present in Gushing's disease with micro-, but not macro- ACT H-secreting pituitary adenoma. This finding agrees with other evidence poin ting toward differences in the hormonal behavior between micro- and ACTH-se creting pituitary macroadenomas.