Different growth hormone (GH) response to GH-releasing peptide and GH-releasing hormone in hyperthyroidism.

Abstract

Altered GH responses to several pharmacological stimuli, including GHRH, have been found in hyperthyroidism. The mechanisms underlying these disturbances have not been fully elucidated. GH-releasing peptide-6 (GHRP-6) is a synthetic hexapeptide that specifically stimulates GH release both in vitro and in vivo. The mechanism of action of GHRP-6 is unknown, but it probably acts by inhibiting the effects of somatostatin on GH release. The aim of this study was to evaluate the effects of GHRP-6 on GH secretion in patients with hyperthyroidism (n = 9) and in control subjects (n = 9). Each subject received GHRP-6 (1 microg/kg, iv), GHRH (100 microg, iv), and GHRP-6 plus GHRH on 3 separate days. GH peak values (mean +/- SE; micrograms per L) were significantly lower in hyperthyroid patients compared to those in control subjects after GHRH alone (9.0 +/- 1.3 vs. 27.0 +/- 5.2) and GHRP-6 plus GHRH (22.5 +/- 3.5 vs. 83.7 +/- 15.2); a lack of the normal synergistic effect of the association of both peptides was observed in thyrotoxicosis. However, a similar GH response was seen in both groups after isolated GHRP-6 injection (31.9 +/- 5.7 vs. 23.2 +/- 3.9). In summary, we have shown that hyperthyroid patients have a normal GH response to GHRP-6 together with a blunted GH responsiveness to GHRH. Our data suggest that thyroid hormones modulate GH release induced by these two peptides in a differential way.

Novel mechanisms of growth hormone regulation: growth hormone-releasing peptides and ghrelin

“…In adrenal insufficiency a 72-h withdrawal of glucocorticoid replacement therapy does not influence the GH responsiveness to GHRP-6 (56). In hyperthyroidism we have observed a decrease in GH responsiveness to GHRH while GHRP-6-induced GH release was maintained, which could suggest that thyroid hormones interfere with GHRH-releasing mechanisms, with preservation of GHRP-6-activated pathways (57). Interestingly, we have recently shown that there is a decrease in the GH response to ghrelin in these patients, suggesting that thyroid hormones interfere with additional pathways of GH release activated by ghrelin (58).…”

Growth Hormone Secretagogues: The Clinical Future

“…The GH release induced by this new stimulus is not affected by ageing or adiposity [15, 16, 17], nor by the absence of adequate hormone replacement therapy of the thyroid and adrenal axes [18, 19, 20], a point relevant if we consider that most GHD adults have other hormone deficiencies in addition to GH. Unlike the insulin tolerance test (ITT), the combined test is not affected by the concomitant presence of diabetes mellitus, which gives it added value [5].…”