Effects of ghrelin, GH-releasing peptide-6 (GHRP-6) and GHRH on GH, ACTH and cortisol release in hyperthyroidism before and after treatment

Abstract

In thyrotoxicosis GH responses to stimuli are diminished and the hypothalamic-pituitary-adrenal axis is hyperactive. There are no data on ghrelin or GHRP-6-induced GH, ACTH and cortisol release in treated hyperthyroidism. We, therefore, evaluated these responses in 10 thyrotoxic patients before treatment and in 7 of them after treatment. GHRH-induced GH release was also studied. Peak GH (mu g/L; mean +/- A SE) values after ghrelin (22.6 +/- A 3.9), GHRP-6 (13.8 +/- A 2.3) and GHRH (4.9 +/- A 0.9) were lower in hyperthyroidism before treatment compared to controls (ghrelin: 67.6 +/- A 19.3; GHRP-6: 25.4 +/- A 2.7; GHRH: 12.2 +/- A 2.8) and did not change after 6 months of euthyroidism (ghrelin: 32.7 +/- A 4.7; GHRP-6: 15.6 +/- A 3.6; GHRH: 7.4 +/- A 2.3), although GH responses to all peptides increased in similar to 50% of the patients. in thyrotoxicosis before treatment ACTH response to ghrelin was two fold higher (107.4 +/- A 26.3) than those of controls (54.9 +/- A 10.3), although not significantly. ACTH response to GHRP-6 was similar in both groups (hyperthyroid: 44.7 +/- A 9.0; controls: 31.3 +/- A 7.9). There was a trend to a decreased ACTH response to ghrelin after 3 months of euthyroidism (35.6 +/- A 5.3; P = 0.052), but after 6 months this decrease was non-significant (50.7 +/- A 14.0). After 3 months ACTH response to GHRP-6 decreased significantly (20.4 +/- A 4.2), with no further changes. in hyperthyroidism before treatment, peak cortisol (mu g/dL) responses to ghrelin (18.2 +/- A 1.2) and GHRP-6 (15.9 +/- A 1.4) were comparable to controls (ghrelin: 16.4 +/- A 1.6; GHRP-6: 13.5 +/- A 0.9) and no changes were seen after treatment. Our results suggest that the pathways of GH release after ghrelin/GHRP-6 and GHRH are similarly affected by thyroid hormone excess and hypothalamic mechanisms of ACTH release modulated by ghrelin/GHSs may be activated in this situation.