Acute decrease in circulating T3 levels enhances, but does not normalise, the GH response to GHRP-6 plus GHRH in thyrotoxicosis

Abstract

In thyrotoxicosis there is an impaired GH response to GHRH, normal GH responsiveness to GHRP-6 and lack of synergistic GH response after simultaneous administration of both peptides. We have previously shown that the GHRH-induced GH release in these patients increases after an acute reduction of circulating T3 values with administration of iopanoic acid, a compound that inhibits peripheral conversion of T4 to T3. We have now studied the effect of a decrease in serum T3 levels on the GH response to GHRP-6 (1 microg/kg) plus GHRH (100 microg) in 9 hyperthyroid patients before and after 15 days of treatment with iopanoic acid (3 g every 3 days) and propylthiouracil (600 mg/day). Nine normal subjects were also studied. In all hyperthyroid patients iopanoic acid induced a rapid decrease and normalisation of serum T3 levels. In these subjects peak GH (microg/l; mean +/- SE) and AUC (microg/l x 120 min) values after GHRP-6 plus GHRH were significantly higher on day 15 compared to pretreatment values (peak, 18.3 +/- 3.0 vs 13.4 +/- 1.9; AUC, 1227.9 +/- 212.9 vs 968.5 +/- 160.4; p<0.05). Despite the significant enhancement of the GH responsiveness to GHRP-6 plus GHRH after treatment with iopanoic acid, this response remained significantly blunted when compared to controls both in terms of peak GH (18.3 +/- 3.0 vs 83.7 +/- 15.2; p<0.05) and AUC values (1227.9 +/- 212.9 vs 4956.5 +/- 889.3; p<0.05). In conclusion, our results show that an acute decrease of circulating T3 levels enhances, but does not normalise, the GH response to GHRP-6 plus GHRH in thyrotoxicosis. This could suggest that circulating T3 does not have a major role in the mechanisms involved in the synergistic effect of these peptides.

Effects of Different Treatments for Hyperthyroidism on the Hypothalamic–pituitary–adrenal Axis

“…This finding raises the possibility that selective T 3 reduction has a stimulatory effect on CRH‐stimulated ACTH secretion. The only other study to examine the acute reduction of T 3 with IA in the pituitary gland also found a growth hormone hyperresponse to administration of growth hormone‐releasing hormone (GHRH) in hyperthyroid patients; nonetheless, under hyperthyroid conditions, the growth hormone response was blunted 24 …”

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

“…We have demonstrated that ghrelin-and GHRP-6-induced GH release are also blunted [18]. Interestingly, an acute reduction in serum circulating T3 levels enhances, but does not normalise the GH response to GHRH and GHRP-6 plus GHRH in thyrotoxicosis [17,19]. The few studies about the effects of antithyroid therapy have shown lack of change [20] or enhancement/restoration of GHRH-induced GH release [12,13] in hyperthyroid patients.…”