Wilson Jessica R, Utz Andrea L, Devin Jessica K
Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN, United States.
Growth Horm IGF Res. 2016 Feb;26:24-31. doi: 10.1016/j.ghir.2015.12.005. Epub 2015 Dec 8.
Body weight blunts the growth hormone (GH) response to provocative stimuli. The appropriate GH cut-off to confirm GH deficiency in obese and overweight patients undergoing the glucagon stimulation test (GST) has recently been questioned. We hypothesized that the peak GH would be inversely related to the nadir blood glucose (BG) after glucagon and that this may be a mechanism influencing peak GH in overweight patients. This retrospective study examined effects of gender, body weight, and BG dynamics on GH response to GST in patients evaluated in our Pituitary Center.
Adult patients who underwent GST from September 2009-2014 were included. Continuous variable comparisons were analyzed using the Mann-Whitney U-test and categorical data by Fisher's Exact Test. Spearman correlation was used to determine associations between continuous variables.
42 patients (N=28, 66.7% female) had sufficient data for analysis. Obese patients (N=26) had a reduced GH response, summarized as GH area under the curve (AUC) (p=0.03 vs. non-obese patients) and higher BG during GST, summarized as AUC (p<0.01 vs. non-obese patients). Obese women (N=19), in particular, stimulated lower (p=0.03 vs. non-obese women) and had a higher nadir BG (p=0.03 vs. non-obese women). While weight correlated with extent (rs=0.35; p=0.02) and timing (rs=0.31; p=0.05) of nadir BG reached, there was no significant correlation between BG dynamics and the GH response in the total population (N=42). Ten patients (7 with pan anterior hypopituitarism, defined as 3 anterior pituitary deficiencies) had a peak GH≤0.1ng/mL during GST. When these subjects with a negligible peak GH response were excluded from the analysis, weight was associated with GH AUC (rs=-0.45; p=0.01), peak GH response (rs=-0.42; p=0.02) and nadir BG (rs=0.48; p<0.01). Furthermore, the nadir BG achieved during GST was inversely related to GH AUC (rs=-0.38; p=0.03) and peak GH (rs=-0.37; p=0.04) such that patients (N=32) with higher nadir BG had lower peak GH in response to glucagon.
Obese patients, particularly women, do not respond as robustly to glucagon stimulation. These data suggest that there exists an altered BG profile during GST in obese individuals, and that a less robust hypoglycemic stimulus may contribute to an impaired GH response. We suggest measuring BG levels during glucagon stimulation testing to assist with clinical interpretation of GH dynamics. The diagnostic accuracy of the GST in patients with known disorders in glucose metabolism and those taking anti-diabetic medications deserves further study.
体重会减弱生长激素（GH）对刺激性刺激的反应。近期，在接受胰高血糖素刺激试验（GST）的肥胖和超重患者中，用于确认生长激素缺乏的合适GH临界值受到了质疑。我们推测，胰高血糖素刺激后生长激素峰值与最低血糖（BG）呈负相关，这可能是影响超重患者生长激素峰值的一种机制。这项回顾性研究调查了性别、体重和血糖动态变化对在我们垂体中心接受评估的患者生长激素对GST反应的影响。
纳入2009年9月至2014年期间接受GST的成年患者。连续变量比较采用曼-惠特尼U检验，分类数据采用费舍尔精确检验。采用斯皮尔曼相关性分析确定连续变量之间的关联。
42例患者（N = 28，66.7%为女性）有足够数据用于分析。肥胖患者（N = 26）的生长激素反应降低，以曲线下面积（AUC）表示（与非肥胖患者相比，p = 0.03），且在GST期间血糖水平更高，以AUC表示（与非肥胖患者相比，p < 0.01）。尤其是肥胖女性（N = 19），其生长激素刺激水平较低（与非肥胖女性相比，p = 0.03），最低血糖水平较高（与非肥胖女性相比，p = 0.03）。虽然体重与达到最低血糖的程度（rs = 0.35；p = 0.02）和时间（rs = 0.31；p = 0.05）相关，但在总体人群（N = 42）中，血糖动态变化与生长激素反应之间无显著相关性。10例患者（7例为全垂体前叶功能减退，定义为3种垂体前叶激素缺乏）在GST期间生长激素峰值≤0.1ng/mL。当将这些生长激素峰值反应可忽略不计的受试者排除在分析之外时，体重与生长激素AUC（rs = -0.45；p = 0.01）、生长激素峰值反应（rs = -0.42；p = 0.02）和最低血糖（rs = 0.48；p < 0.01）相关。此外，GST期间达到的最低血糖与生长激素AUC（rs = -0.38；p = 0.03）和生长激素峰值（rs = -0.37；p = 0.04）呈负相关，因此，最低血糖较高的患者（N = 32）对胰高血糖素刺激的生长激素峰值较低。
肥胖患者，尤其是女性，对胰高血糖素刺激的反应不强烈。这些数据表明，肥胖个体在GST期间血糖谱发生改变，较弱的低血糖刺激可能导致生长激素反应受损。我们建议在胰高血糖素刺激试验期间测量血糖水平，以辅助生长激素动态变化的临床解读。GST在已知糖代谢紊乱患者和服用抗糖尿病药物患者中的诊断准确性值得进一步研究。
