Effect of low-dose oral and intravenous dexamethasone administration on growth hormone secretion in children.

Acute dexamethasone administration (2 mg/m2 i.v. and 4 mg orally) increases growth hormone (GH) release in children. We evaluated the effect of a low intravenous dose (1 mg/m2) of dexamethasone on GH secretion in 8 short normal children and in 6 GH-deficient children. There was a significant GH increase at 120, 150 and 180 min in short normal children (maximal value: 18.9 +/- 2.1 micrograms/l; mean +/- EP), compared to placebo administration. In contrast, no significant GH elevation was seen in GH-deficient children (1.3 +/- 0.4 micrograms/l). There was no difference in the GH response after intravenous dexamethasone and oral clonidine in these same 8 short normal children and 6 GH-deficient children. Although no significant GH release was observed after dexamethasone or clonidine in GH deficiency, an increase in GH after GH-releasing hormone was seen (6.1 +/- 1.9 micrograms/l). There was a significant GH increase (18.5 +/- 3.3 micrograms/l) after low-dose (2-mg) oral dexamethasone administration in another 8 short normal children, which was similar to values after intravenous injection. No side effects were noted after intravenous or oral dexamethasone. In conclusion, low-dose intravenous or oral dexamethasone administration causes a marked GH release in short normal children, probably mediated by hypothalamic structures.

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 micrograms i.v.), GHRP-6 (1 microgram/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-1 by radioimmunoassay. RESULTS: Hypothyroid patients had markedly lower peak GH values (mean +/- SE micrograms/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.