Effects of ghrelin, GH-releasing peptide-6 (GHRP-6) and GHRH on GH, ACTH and cortisol release in hyperthyroidism before and after treatment.
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 (μg/L; mean ± SE) values after ghrelin (22.6 ± 3.9), GHRP-6 (13.8 ± 2.3) and GHRH (4.9 ± 0.9) were lower in hyperthyroidism before treatment compared to controls (ghrelin: 67.6 ± 19.3; GHRP-6: 25.4 ± 2.7; GHRH: 12.2 ± 2.8) and did not change after 6 months of euthyroidism (ghrelin: 32.7 ± 4.7; GHRP-6: 15.6 ± 3.6; GHRH: 7.4 ± 2.3), although GH responses to all peptides increased in ~50% of the patients. In thyrotoxicosis before treatment ACTH response to ghrelin was two fold higher (107.4 ± 26.3) than those of controls (54.9 ± 10.3), although not significantly. ACTH response to GHRP-6 was similar in both groups (hyperthyroid: 44.7 ± 9.0; controls: 31.3 ± 7.9). There was a trend to a decreased ACTH response to ghrelin after 3 months of euthyroidism (35.6 ± 5.3; P = 0.052), but after 6 months this decrease was non-significant (50.7 ± 14.0). After 3 months ACTH response to GHRP-6 decreased significantly (20.4 ± 4.2), with no further changes. In hyperthyroidism before treatment, peak cortisol (μg/dL) responses to ghrelin (18.2 ± 1.2) and GHRP-6 (15.9 ± 1.4) were comparable to controls (ghrelin: 16.4 ± 1.6; GHRP-6: 13.5 ± 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.
Molica
Patricia
P
Division of Endocrinology, Universidade Federal de São Paulo, UNIFESP-EPM, Rua Pedro de Toledo 910, 04039-002, São Paulo, Brazil. patmolica@gmail.com
Nascif
Sergio Oliva
SO
Correa-Silva
Silvia Regina
SR
de Sá
Larissa Bianca Paiva Cunha
LB
Vieira
José Gilberto Henriques
JG
Lengyel
Ana-Maria Judith
AM
D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D005260:Female; D054439:Ghrelin / Q000627:therapeutic use*; D013006:Growth Hormone / Q000097:blood*; D013007:Growth Hormone-Releasing Hormone / Q000627:therapeutic use*; D006728:Hormones / Q000627:therapeutic use; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D009842:Oligopeptides / Q000627:therapeutic use*; D013971:Thyrotoxicosis / Q000097:blood / Q000188:drug therapy*
D000893:Anti-Inflammatory Agents; D054439:Ghrelin; D006728:Hormones; D009842:Oligopeptides; C041048:growth hormone releasing hexapeptide; D000324:Adrenocorticotropic Hormone; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D006854:Hydrocortisone