Enhancement of the peripheral sensitivity to growth hormone in adults with GH deficiency
European Journal of Endocrinology v.145, i.3 29sep01
G Aimaretti, G Fanciulli1, S Bellone, M Maccario, E Arvat, G Delitala1, F Camanni and E Ghigo
Division of Endocrinology, Department of Internal Medicine, University of Turin, Italy and 1Division of Internal Medicine, University of Sassari, Italy(Correspondence should be addressed to E Ghigo, Divisione di Endocrinologia, Ospedale Molinette, C.so Dogliotti 14, 10126 Torino, Italy)
Abstract
Objective: Adults with severe GH deficiency (GHD) need 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. Aim of the present study was to define the minimal rhGH dose able to increase both IGF-I and IGFBP-3 levels in GH deficiency and to verify the possible change in GH sensitivity.
Design and patients: To this goal, we study the effect of 4 day treatments with 3 rhGH doses (1.25, 2.5 and 5.0 mg/kg/day) on IGF-I and IGFBP-3 levels in 25 panhypopituitary adults with severe GH deficiency (GHD, 12M and 13F, age: 44.5±3.0 years, BMI: 27.0±0.9 kg/m2) and 21 normal young adult volunteers (NV, 12M and 9F, 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 dose of 1.25 mg/kg rhGH did not modify IGF-I levels. The dose of 2.5 mg/Kg rhGH significantly increased IGF-I levels in men (P<0.001) but not in women, while the dose of 5.0 mg/kg increased IGF-I levels in both sexes (P<0.001). IGFBP-3 levels were not modified by any rhGH dose. In GHD all rhGH doses increased IGF-I levels 12 h both after the first (P<0.01) and the fourth rhGH dose (P<0.001). At the end of treatment IGF-I percent increases were higher (P<0.001) in GHD than those in NV. Differently from in NV, in GHD the IGF-I response to short term stimulation with rhGH was independent of gender. Moreover GHD patients showed IGFBP-3 increases after the fourth administration of both 2.5 and 5.0 mg/kg rhGH.
Conclusion: The results of the present study demonstrate that the minimal rhGH dose able to increase IGF-1 and IGFBP-3 levels in GHD is lower than in normal subjects, at least after a very short treatment. This evidence suggests an enhanced peripheral GH sensitivity in GH deprivation.
source: http://www.eje.org/eje/145/3/default.htm 29aug01
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