Misra Madhusmita, Miller Karen K, Almazan Cecilia, Worley Megan, Herzog David B, Klibanski Anne
Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, BUL 457, 55 Fruit Street, Boston, Massachusetts 02114, USA.
J Clin Endocrinol Metab. 2005 May;90(5):2580-7. doi: 10.1210/jc.2004-2041. Epub 2005 Feb 15.
We have previously demonstrated that girls with anorexia nervosa (AN) have higher levels of GH and cortisol and lower levels of estradiol than healthy adolescents. The effects of endocrine alterations on regional body composition in AN, however, have not been reported. We, therefore, enrolled 23 adolescent girls with AN and 20 healthy girls of comparable maturity in a study examining regional body composition. Levels of estradiol and IGF-I, as well as measures of GH and cortisol concentration (using cluster analysis of data obtained from frequent sampling q30' for 12 h overnight) were examined to determine hormonal determinants of regional body composition in adolescent girls with AN and controls. Girls with AN were followed for 1 yr and examined again at weight recovery (10% increase in body mass index) (n = 11). Percent trunk fat and trunk to extremity fat ratio (T/E fat) were significantly reduced in girls with AN compared with healthy adolescents (P = 0.001 and 0.01, respectively). Percent trunk lean mass and trunk to extremity lean mass ratio (T/E lean) were higher in AN than in controls (P = 0.01 and 0.009); percent extremity lean mass was lower in AN (P = 0.009). In healthy controls, total area under the curve (AUC) for GH correlated inversely with percent trunk fat and T/E fat (r = -0.66, P = 0.002 and r = -0.62, P = 0.003). Similar correlations were observed between other measures of GH concentration (mean and nadir) and percent trunk fat and T/E fat. No relationship was observed between GH concentration and regional lean mass or between cortisol concentration and regional body composition. In contrast, GH concentration did not predict regional body composition in adolescents with AN on regression analysis. However, nadir cortisol concentration correlated inversely with percent extremity lean mass (r = -0.49; P = 0.02) and positively with percent trunk lean mass and T/E lean (r = 0.48, P = 0.03; and r = 0.49, P = 0.02) in girls with AN. A similar trend was observed between other measures of cortisol concentration (mean cortisol and AUC) and percent trunk lean mass and T/E lean in AN. Trunk fat was lowest in girls with AN who had high GH but low cortisol levels (based on median values), whereas some preservation of trunk fat was observed in girls with low GH and high cortisol levels. Weight recovery occurred in seven of 11 girls with low GH and high cortisol values; however, only two of the nine girls with high GH and low cortisol recovered weight. High GH with lower cortisol levels may thus be a marker of greater severity of AN. Our results suggest that in healthy controls, GH concentration predicts regional body composition and favors a redistribution of body fat such that T/E fat ratio decreases. In AN, however, high levels of GH and cortisol have contrasting associations with fat mass. High cortisol levels in AN predict a redistribution of lean body mass such that extremity lean mass decreases. Further studies are necessary to better understand the implications of these data.
我们之前已经证明,患有神经性厌食症(AN)的女孩比健康青少年具有更高水平的生长激素(GH)和皮质醇,以及更低水平的雌二醇。然而,内分泌改变对AN患者局部身体成分的影响尚未见报道。因此,我们招募了23名患有AN的青春期女孩和20名成熟度相当的健康女孩,进行一项关于局部身体成分的研究。检测了雌二醇和胰岛素样生长因子-I(IGF-I)的水平,以及GH和皮质醇浓度的测量值(通过对夜间12小时每隔30分钟频繁采样获得的数据进行聚类分析),以确定患有AN的青春期女孩和对照组局部身体成分的激素决定因素。对患有AN的女孩随访1年,并在体重恢复时(体重指数增加10%)再次进行检查(n = 11)。与健康青少年相比,患有AN的女孩躯干脂肪百分比和躯干与四肢脂肪比(T/E脂肪)显著降低(分别为P = 0.001和0.01)。AN患者的躯干瘦体重百分比和躯干与四肢瘦体重比(T/E瘦)高于对照组(P = 0.01和0.009);四肢瘦体重百分比在AN患者中较低(P = 0.009)。在健康对照组中,GH的曲线下总面积(AUC)与躯干脂肪百分比和T/E脂肪呈负相关(r = -0.66,P = 0.002和r = -0.62,P = 0.003)。在GH浓度的其他测量值(平均值和最低点)与躯干脂肪百分比和T/E脂肪之间也观察到类似的相关性。在回归分析中,未观察到GH浓度与局部瘦体重之间的关系,也未观察到皮质醇浓度与局部身体成分之间的关系。然而,在患有AN的青少年中,最低点皮质醇浓度与四肢瘦体重百分比呈负相关(r = -0.49;P = 0.02),与躯干瘦体重百分比和T/E瘦呈正相关(r = 0.48,P = 0.03;r = 0.49,P = 0.02)。在AN患者中,皮质醇浓度的其他测量值(平均皮质醇和AUC)与躯干瘦体重百分比和T/E瘦之间也观察到类似趋势。GH水平高但皮质醇水平低的患有AN的女孩躯干脂肪最低(基于中位数),而GH水平低且皮质醇水平高的女孩则观察到一些躯干脂肪的保留。11名GH水平低且皮质醇水平高的值的女孩中有7名体重恢复;然而,9名GH水平高且皮质醇水平低的女孩中只有2名恢复了体重。因此,GH水平高且皮质醇水平低可能是AN病情更严重的一个标志。我们的结果表明,在健康对照组中,GH浓度可预测局部身体成分,并有利于身体脂肪的重新分布,使T/E脂肪比降低。然而,在AN患者中,高水平的GH和皮质醇与脂肪量有相反的关联。AN患者中高皮质醇水平预示着瘦体重的重新分布,使四肢瘦体重减少。需要进一步研究以更好地理解这些数据的意义。