Ghrelin and GHRP-6-induced ACTH and cortisol release in thyrotoxicosis

Abstract

Thyrotoxicosis might alter the hypothalamic-pituitary-adrenal (HPA) axis. We evaluated the effects of ghrelin and GHRP-6 on the HPA axis in 20 hyperthyroid patients and in 9 controls. Mean basal cortisol (microg/dl) and ACTH (pg/ml) levels were higher in hyperthyroidism (cortisol: 10.7 +/- 0.7; ACTH: 21.5 +/- 2.9) compared to controls (cortisol: 8.1 +/- 0.7; ACTH: 13.5 +/- 1.8). In thyrotoxicosis Delta AUC cortisol values (microg/dl.90 min) after ghrelin (484 +/- 80) and GHRP-6 (115 +/- 63) were similar to controls (ghrelin: 524 +/- 107; GHRP-6: 192 +/- 73). A significant increase in Delta AUC ACTH (pg/ml x 90 min) after ghrelin was observed in thyrotoxicosis (4,189 +/- 1,202) compared to controls (1,499 +/- 338). Delta AUC ACTH values after GHRP-6 were also higher, although not significantly (patients: 927 +/- 330; controls: 539 +/- 237). In summary, our results suggest that ghrelin-mediated pathways of ACTH release might be activated by thyroid hormone excess, but adrenocortical reserve is maintained.

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

“…However, we have not observed substantial differences in cortisol responses to ghrelin and GHRP-6 in our patients compared to controls, both before and during treatment. This is in agreement with our previous findings [37] and also of reports of normal cortisol responses to hypoglycemia and CRH in thyrotoxicosis [11,14,28,34,35]. Our results, therefore, suggest that adrenocortical responsiveness to ghrelin and GHRP-6 are normal in thyrotoxic patients.…”

“…High basal ACTH levels have been found, which decrease with treatment, reinforcing this hypothesis [33,35,36]. Previous data obtained by us suggest that ACTH responses to ghrelin and GHRP-6 might be enhanced in thyrotoxicosis, while cortisol responsiveness is normal in these patients [37].…”

“…In agreement with these findings, our hyperthyroid group presented a two-fold increase in ACTH response to ghrelin compared to controls before treatment, and GHRP-6-induced ACTH release was also higher, although not reaching statistical significance in both cases. This could be due to the small number of patients in our study group, as we have previously shown hyperresponsiveness of ACTH to ghrelin and GHRP-6 in a larger group of thyrotoxic patients [37]. Moreover, our data show a decrease in ACTH response to both peptides when we excluded the only patient who had an increase in ACTH values after ghrelin during treatment.…”

Ghrelin Gene Products and the Regulation of Food Intake and Gut Motility

“…GH release after acyl ghrelin, GHRP-6, and GHRH administration was decreased in thyrotoxicosis, whereas acyl ghrelin's ability to increase glucose levels was not altered in thyrotoxicosis (Nascif et al, 2007). Acyl ghrelin-mediated pathways of adrenocorticotropin release might be activated by thyroid hormone excess, but adrenocortical reserve was maintained during thyrotoxicosis (Nascif et al, 2009). These observations suggest that thyroid hormone excess interferes with GH-releasing and affects adrenocorticotropin-releasing pathways activated by acyl ghrelin.…”

Relative Adrenocortical Insufficiency Following Radioactive Iodine Therapy for Graves’ Disease: A Report of Two Cases

“…Then through close follow-up, we discovered that the patient no longer needed glucocorticoid replacement and achieved normalized cortisol and ACTH as FT3, FT4 trended down, which confirmed our suspicion that this was a transient adrenocortical insufficiency. 27 On this base, we started to evaluate adrenocortical function for patients with severe thyrotoxicosis after 131 I administration. Most patients had normal basal cortisol except the second case.…”