GROWTH-HORMONE RESPONSES TO GH-RELEASING PEPTIDE (GHRP-6) IN HYPOTHYROIDISM

OBJECTIVE Both spontaneous and stimulated GH secretion are reduced in patients with hypothyroidism. The mechanisms involved in these alterat ions are not yet fully understood, GHRP-6 is a synthetic hexapeptide t hat releases GH both in vivo and in vitro., Its mechanism of action is unknown, but there is evidence that this peptide acts as a functional somatostatin antagonist at pituitary level. The aim of this study was to evaluate the GH response to GHRP-6 in patients with primary hypoth yroidism and in normal controls, DESIGN Patients with hypothyroidism a nd normal controls were randomly submitted to 3 tests with GHRH (100 m u g i.v.), GHRP-6 (1 mu g/kg i.v.) and GHRH + GHRP-6, on separate days . PATIENTS Eleven patients with primary hypothyroidism were compared w ith 10 control subjects, MEASUREMENTS GH, TSH and free T4 were measure d by immunofluorometric assay and IGF-I by radioimmunoassay. RESULTS H ypothyroid patients had markedly lower peak GH values (mean +/- SE mu g/l) after GHRH administration (4.1 +/- 0.9) compared to control subje cts (24.9 +/- 5.1). After GHRP-6 injection hypothyroid patients had a significantly higher GH release (12.6 +/- 1.9) than that obtained with GHRH, while in control subjects GH values were similar (22.1 +/- 3.6) . No significant differences in peak GH responses were observed follow ing the administration of either GHRP-6 alone (controls 22.1 +/- 3.6; patients 12.6 +/- 1.9) or in combination with GHRH (controls 77.4 +/- 15.0; patients 52.8 +/- 10.9), despite the trend to smaller responses in hypothyroid patients, CONCLUSION We have shown that patients with p rimary hypothyroidism have higher GH responses to GHRP-6 than to GHRH, which are markedly blunted. When GHRP-6 was associated with GHRH, a s ignificant increase in the GH response was observed in these patients, which could suggest a role for somatostatin in this process. Our data suggest that thyroid hormones modulate GH release induced by GHRH and GHRP-6 through different mechanisms. However, additional studies are necessary to further elucidate this hypothesis.