Enhancement of the peripheral sensitivity to growth hormone in adults with GH deficiency

Objective: Adults with severe GH deficiency (GHD) need recombinant human growth hormone (rhGH) replacement to restore body composition, structure functions and metabolic abnormalities. The optimal rhGH dose for replacement has been progressively reduced to avoid side effects. The aim of the present study was to define the minimal rhGH dose able to increase both IGF-I and IGF binding protein (BP)-3 levels in GHD and to verify the possible change in GH sensitivity. Design and patients: To this goal, we studied the effect of 4-day treatment with 3 rhGH doses (1.25, 2.5 and 5.0 μg/kg/day) on IGF-I and IGFBP-3 levels in 25 panhypopituitary adults with severe GHD (12 males and 13 females, age: 44.5 ± 3.0 years, body mass index (BMI): 27.0 ± 0.9 kg/m²) and 21 normal young adult volunteers (NV, 12 males and 9 females, age: 30.5 ± 2.0 years, BMI: 20.8 ± 0.5 kg/m²). Results: Basal IGF-I and IGFBP-3 levels in GHD were lower (P < 0.001) than in NV. In NV the 1.25 μg/kg dose of rhGH did not modify IGF-I levels. The dose of 2.5 μg/kg rhGH significantly increased IGF-I levels in men (P < 0.001) but not in women, while the 5.0 μg/kg dose increased IGF-I levels in both sexes (P < 0.001). IGFBP-3 levels were not modified by any of the administered rhGH doses. In GHD patients, all rhGH doses increased IGF-I levels 12 h after both the first (P < 0.01) and the fourth rhGH dose (P < 0.001). At the end of treatment percentage increases in IGF-I were higher (P < 0.001) in GHD patients than in NV. In contrast with NV, in GHD patients the IGF-I response to short-term stimulation with rhGH was independent of gender. Moreover, GHD patients showed increases in IGFBP-3 after the fourth administration of both 2.5 and 5.0 μg/kg rhGH. Conclusion: The results of the present study demonstrate that the minimal rhGH dose able to increase IGF-I and IGFBP-3 levels in GHD patients is lower than in normal subjects, at least after a very short treatment. This evidence suggests an enhanced peripheral GH sensitivity in GH deprivation.