IGF-I levels rise and GH responses to GHRH decrease during long-term prednisone treatment in man.

Glucocorticoid excess is associated with a blunted GH response to GHRH. IGF-I levels in hypercortisolism are controversial and have been reported as low, normal or high. The aim of this study was to evaluate longitudinally time-dependent changes in the GH response to GHRH, IGF-I, IGFBP-3 and albumin values in patients during corticotherapy. Six patients received GHRH before and after one week and one month of prednisone administration (20-60 mg/d, orally). IGF-I, IGFBP-3 and albumin were determined in each test, at time 0. Ten normal controls were also evaluated in one occasion. There were no differences in basal GH values, GH response to GHRH, IGF-I and IGFBP-3 levels between controls and patients before starting corticotherapy. Albumin (g/l; mean+/-SE) values were lower in patients before treatment (31+/-4) than in controls (43+/-1). After one week of prednisone administration there was a significant decrease in peak GH (microg/l) levels (before: 18.8+/-7.4; 1 week: 5.0+/-1.3), which was maintained after one month (8.1+/-3.5). IGF-I (microg/l) levels increased significantly, from 145+/-23 to 205+/-52 after one week of therapy, reaching levels of 262+/-32 after one month. IGFBP-3 (mg/l) values did not increase significantly (before: 2.1+/-0.2; 1 week: 2.5+/-0.3; 1 month: 2.8+/-0.2). Albumin levels showed a significant rise both after one week (36+/-4) and one month (42+/-3) of corticotherapy. In summary, we observed a marked decrease in the GH response to GHRH after one week and one month of prednisone administration associated with an increase in circulating IGF-I and albumin values. The physiological implications of these findings are still uncertain. It is possible that glucocorticoids increase hepatic IGF-I and albumin synthesis, although other mechanisms may have a role.

Different effects of growth hormone releasing peptide (GHRP-6) and GH-releasing hormone on GH release in endogenous and exogenous hypercortisolism.

OBJECTIVE: Chronic hypercortisolism is associated with decreased GH responsiveness to GHRH. GHRP-6 is a synthetic hexapeptide that releases GH in several species, including man. As GHRH and GHRP-6 apparently stimulate GH release by different mechanisms, we evaluated the GH responses to these peptides in patients with endogenous and exogenous glucocorticoid excess and also in control subjects. DESIGN: Six patients with endogenous hypercortisolism, nine with exogenous glucocorticoid excess and 10 normal controls were submitted to three tests, in random order, with GHRH (100 micrograms), GHRP-6 (1 microgram/ kg) or GHRP+GHRP-6, in the same doses, i.v., on separate days. MEASUREMENTS: GH was measured by immunofluorometric assay. IGF-I was determined by radioimmunoassay. Plasma glucose was measured by the glucose-oxidase technique. RESULTS: Peak GH values (mean +/- SE; microgram/l) after GHRH were significantly blunted in endogenous (2.0 +/- 0.7) and exogenous (3.6 +/- 1.2) hypercortisolaemic patients compared to controls (24.9 +/- 6.1). The endogenous group had lower peak GH values after GHRP-6 alone (7.7 +/- 1.9) or together with GHRH (18.8 +/- 5.8) than those observed in controls (GHRP-6: 22.1 +/- 3.6; GHRH+GHRP-6: 77.4 +/- 15.0) and in exogenous hypercortisolism (27.4 +/- 6.2 and 78.1 +/- 19.9). There were no differences in the GH responses to GHRP-6 alone or in combination with GHRH when controls were compared to the exogenous group. No changes in plasma IGF-I and glucose levels were observed. CONCLUSIONS: Our results suggest that hypercortisolism had a different effect on the GH-releasing mechanisms stimulated by GHRH and GHRP-6. Moreover, in endogenous hypercortisolism both GHRH and GHRP-6 pathways are affected, while in the exogenous group GHRP-6 releasing mechanisms are apparently preserved.