生长激素缺乏的成年人外周对生长激素敏感性的增强。

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

作者信息

Aimaretti G, Fanciulli G, Bellone S, Maccario M, Arvat E, Delitala G, Camanni F, Ghigo E

机构信息

Division of Endocrinology, Department of Internal Medicine, University of Turin, 10126 Turin, Italy.

出版信息

Eur J Endocrinol. 2001 Sep;145(3):267-72. doi: 10.1530/eje.0.1450267.

DOI:10.1530/eje.0.1450267

PMID:11517006

Abstract

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 microg/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/m(2)) and 21 normal young adult volunteers (NV, 12 males and 9 females, age: 30.5+/-2.0 years, BMI: 20.8+/-0.5 kg/m(2)).

RESULTS

Basal IGF-I and IGFBP-3 levels in GHD were lower (P<0.001) than in NV. In NV the 1.25 microg/kg dose of rhGH did not modify IGF-I levels. The dose of 2.5 microg/kg rhGH significantly increased IGF-I levels in men (P<0.001) but not in women, while the 5.0 microg/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 microg/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.

摘要

目的

重度生长激素缺乏（GHD）的成年人需要重组人生长激素（rhGH）替代治疗，以恢复身体成分、结构功能及代谢异常。为避免副作用，rhGH替代治疗的最佳剂量已逐步降低。本研究的目的是确定能使GHD患者胰岛素样生长因子-I（IGF-I）和IGF结合蛋白（BP）-3水平均升高的最小rhGH剂量，并验证GH敏感性可能发生的变化。

设计与患者

为此，我们研究了3种rhGH剂量（1.25、2.5和5.0μg/kg/天）连续4天治疗对25例垂体功能减退的重度GHD成年患者（12例男性和13例女性，年龄：44.5±3.0岁，体重指数（BMI）：27.0±0.9kg/m²）及21名正常青年志愿者（NV，12例男性和9例女性，年龄：30.5±2.0岁，BMI：20.8±0.5kg/m²）IGF-I和IGFBP-3水平的影响。

结果

GHD患者的基础IGF-I和IGFBP-3水平低于NV（P<0.001）。在NV中，1.25μg/kg剂量的rhGH未改变IGF-I水平。2.5μg/kg rhGH剂量使男性的IGF-I水平显著升高（P<0.001），但女性未升高，而5.0μg/kg剂量使两性的IGF-I水平均升高（P<0.001）。所给予的任何rhGH剂量均未改变IGFBP-3水平。在GHD患者中，所有rhGH剂量在首次（P<0.01）和第四次rhGH剂量后12小时均使IGF-I水平升高（P<0.001）。治疗结束时，GHD患者IGF-I的升高百分比高于NV（P<0.001）。与NV不同，在GHD患者中，rhGH短期刺激后的IGF-I反应与性别无关。此外，GHD患者在给予2.5和5.0μg/kg rhGH第四次给药后，IGFBP-3水平升高。