Murray Robert D, Adams Judith E, Shalet Stephen M
Department of Endocrinology, Christie Hospital, Manchester M20 4BX, United Kingdom.
J Clin Endocrinol Metab. 2004 Apr;89(4):1586-91. doi: 10.1210/jc.2003-030761.
The current biochemical definition of severe GH deficiency (stimulated peak GH < 3 micro g/liter) provides good separation of GH-deficient (GHD) adults from normal subjects, although it may not account for all patients with impaired GH secretion. The vast majority of normal subjects display a peak GH level in excess of 7 micro g/liter in response to the insulin tolerance test. Using a peak GH response of 7 micro g/liter as an arbitrary upper limit, we investigated the effects of partial GH deficiency (GH insufficiency, GHI; peak GH response of 3-7 micro g/liter) on the body composition of hypopituitary adults. GHD adults (n = 30, peak GH < 3 micro g/liter) were of shorter stature than the controls. Body mass index was not significantly increased, but waist/hip ratio (0.885 vs. 0.818, P = 0.001) and skinfold thickness (78.2 vs. 59.6 mm, P = 0.003) were greater than control subjects. Bioimpedance analysis revealed these patients to have reduced lean body mass (LBM) (44.4 vs. 51.2 kg, P = 0.023) and increased fat mass (FM) (25.7 vs. 18.4 kg, P = 0.039). Dual-energy x-ray absorptiometry (DXA) analysis of body composition confirmed reduced LBM (43.6 vs. 50.6 kg, P = 0.010) and increased FM (26.0 vs. 19.2 kg, P = 0.015). The excess FM was observed to be primarily truncal in distribution. Similarly, GHI adults were of shorter stature but with increased waist/hip ratio (0.871 vs. 0.818, P = 0.006) and skinfold thickness (80.8 vs. 59.6 mm, P = 0.003), compared with controls. Bioimpedance analysis revealed a reduction in LBM (44.9 vs. 51.2 kg, P = 0.020). DXA studies confirmed the reduced LBM (45.0 vs. 50.6 kg, P = 0.041) and additionally noted an increase in percent FM (32.9 vs. 27.4%, P = 0.019). All measures of body composition in the GHI patients were intermediate between those of the controls and GHD patients. Serum leptin levels were significantly elevated in both the GHD (41.5 vs. 20.7 ng/ml, P = 0.009) and GHI (36.7 vs. 20.7 ng/ml, P = 0.022) adults, compared with healthy controls. The excess FM observed using DXA in the GHD and GHI adults equated to 6.5 kg (8%) and 3.5 kg (5.5%), respectively, relative to healthy controls. In summary, we have shown that adults with GHI have abnormalities of body composition characteristic of GHD. The degree of abnormality of body composition lies between that of healthy subjects and GHD adults and correlates with the IGF-I level. Any future trials of GH replacement in patients with GHI must await further studies to establish the exact impact of this relative deficiency on the broad spectrum of biological end points influenced by GH status.
目前对严重生长激素缺乏(刺激后生长激素峰值<3μg/升)的生化定义能够很好地区分生长激素缺乏(GHD)成人与正常受试者,尽管它可能无法涵盖所有生长激素分泌受损的患者。绝大多数正常受试者在胰岛素耐量试验中的生长激素峰值水平超过7μg/升。以7μg/升的生长激素峰值反应作为一个任意的上限,我们研究了部分生长激素缺乏(生长激素不足,GHI;生长激素峰值反应为3 - 7μg/升)对垂体功能减退成人身体成分的影响。GHD成人(n = 30,生长激素峰值<3μg/升)的身高低于对照组。体重指数没有显著增加,但腰臀比(0.885对0.818,P = 0.001)和皮褶厚度(78.2对59.6mm,P = 0.003)高于对照组。生物电阻抗分析显示这些患者的瘦体重(LBM)减少(44.4对51.2kg,P = 0.023),脂肪量(FM)增加(25.7对18.4kg,P = 0.039)。双能X线吸收法(DXA)对身体成分的分析证实了LBM减少(43.6对50.6kg,P = 0.010)和FM增加(26.0对19.2kg,P = 0.015)。观察到多余的FM主要分布在躯干。同样,与对照组相比,GHI成人身高较矮,但腰臀比增加(0.871对0.818,P = 0.006)和皮褶厚度增加(80.8对59.6mm,P = 0.003)。生物电阻抗分析显示LBM减少(44.9对51.2kg,P = 0.020)。DXA研究证实了LBM减少(四十五点零对50.6kg,P = 0.041),并额外指出FM百分比增加(32.9对27.4%,P = 0.019)。GHI患者身体成分的所有测量值都介于对照组和GHD患者之间。与健康对照组相比,GHD成人(41.5对20.7ng/ml,P = 0.009)和GHI成人(36.7对20.7ng/ml,P = 0.022)的血清瘦素水平均显著升高。使用DXA观察到,相对于健康对照组,GHD和GHI成人中多余的FM分别相当于6.5kg(8%)和3.5kg(5.5%)。总之,我们已经表明,患有GHI的成人具有GHD特有的身体成分异常。身体成分异常的程度介于健康受试者和GHD成人之间,并与胰岛素样生长因子-I水平相关。未来任何关于GHI患者生长激素替代治疗的试验都必须等待进一步的研究,以确定这种相对缺乏对受生长激素状态影响的广泛生物学终点的确切影响。