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 alterations are not yet fully understood. GHRP-6 is a synthetic hexapeptide that 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 hypothyroidism and in normal controls. DESIGN Patients with hypothyroidism and normal controls were randomly submitted to 3 tests with GHRH (100 μg i.v.), GHRP-6 (1 μg/kg i.v.) and GHRH + GHRP-6, on separate days. PATIENTS Eleven patients with primary hypothyroidism were compared with 10 control subjects. MEASUREMENTS GH, TSH and free T4 were measured by immunofluorometric assay and IGF-I by radioimmunoassay. RESULTS Hypothyroid patients had markedly lower peak GH values (mean ± SE μg/l) after GHRH administration (4.1 ± 0.9) compared to control subjects (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 following 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 primary hypothyroidism have higher GH responses to GHRP-6 than to GHRH, which are markedly blunted. When GHRP-6 was associated with GHRH, a significant 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.