用于评估成人生长激素（GH）和下丘脑-垂体-肾上腺（HPA）轴的胰高血糖素刺激试验中GH和皮质醇的修订切点：一项前瞻性随机多中心研究的结果
Revised GH and cortisol cut-points for the glucagon stimulation test in the evaluation of GH and hypothalamic-pituitary-adrenal axes in adults: results from a prospective randomized multicenter study.
作者信息
Hamrahian Amir H, Yuen Kevin C J, Gordon Murray B, Pulaski-Liebert Karen J, Bena James, Biller Beverly M K
机构信息
Department of Endocrinology, Diabetes and Metabolism, Cleveland Clinic, Cleveland, OH, 44022, USA.
Department of Endocrinology, Medical Subspecialty Institute, Cleveland Clinic Abu Dhabi, 7th Floor, Swing Wing, Al Maryah Island, PO Box 112412, Abu Dhabi, UAE.
出版信息
Pituitary. 2016 Jun;19(3):332-41. doi: 10.1007/s11102-016-0712-7.
CONTEXT
Recent studies suggest using lower GH cut-points for the glucagon stimulation test (GST) in diagnosing adult GH deficiency (GHD), especially in obese patients. There are limited data on evaluating GH and hypothalamic-pituitary-adrenal (HPA) axes using weight-based dosing for the GST.
OBJECTIVE
To define GH and cortisol cut-points to diagnose adult GHD and secondary adrenal insufficiency (SAI) using the GST, and to compare fixed-dose (FD: 1 or 1.5 mg in patients >90 kg) with weight-based dosing (WB: 0.03 mg/kg). Response to the insulin tolerance test (ITT) was considered the gold standard, using GH and cortisol cut-points of ≥3 ng/ml and ≥18 µg/dL, respectively.
DESIGN
28 Patients with hypothalamic-pituitary disease and 1-2 (n = 14) or ≥3 (n = 14) pituitary hormone deficiencies, and 14 control subjects matched for age, sex, estrogen status and body mass index (BMI) underwent the ITT, FD- and WB-GST in random order.
RESULTS
Age, sex ratio and BMI were comparable between the three groups. The best GH cut-point for diagnosis of GHD was 1.0 (92 % sensitivity, 100 % specificity) and 2.0 ng/mL (96 % sensitivity and 100 % specificity) for FD- and WB-GST, respectively. Age negatively correlated with peak GH during FD-GST (r = -0.32, P = 0.04), but not WB-GST. The best cortisol cut-point for diagnosis of SAI was 8.8 µg/dL (92 % sensitivity, 100 % specificity) and 11.2 µg/dL (92 % sensitivity and 100 % specificity) for FD-GST and WB-GST, respectively. Nausea was the most common side effect, and one patient had a seizure during the FD-GST.
CONCLUSION
The GST correctly classified GHD using GH cut-points of 1 ng/ml for FD-GST and 2 ng/ml for WB-GST, hence using 3 ng/ml as the GH cut-point will misclassify some GH-sufficient adults. The GST may also be an acceptable alternative to the ITT for evaluating the HPA axis utilizing cortisol cut-points of 9 µg/dL for FD-GST and 11 µg/dL for WB-GST.
背景
最近的研究表明，在诊断成人生长激素缺乏症（GHD）时，尤其是在肥胖患者中，可使用较低的生长激素切点进行胰高血糖素刺激试验（GST）。关于使用基于体重的剂量进行GST来评估生长激素和下丘脑 - 垂体 - 肾上腺（HPA）轴的数据有限。
目的
确定使用GST诊断成人GHD和继发性肾上腺功能不全（SAI）的生长激素和皮质醇切点，并比较固定剂量（FD：体重>90 kg的患者为1或1.5 mg）与基于体重的剂量（WB：0.03 mg/kg）。将胰岛素耐量试验（ITT）的反应视为金标准，生长激素和皮质醇切点分别≥3 ng/ml和≥18 μg/dL。
设计
28例患有下丘脑 - 垂体疾病且有1 - 2种（n = 14）或≥3种（n = 14）垂体激素缺乏的患者，以及14名年龄、性别、雌激素状态和体重指数（BMI）匹配的对照受试者，随机顺序接受ITT、FD - GST和WB - GST。
结果
三组之间的年龄、性别比例和BMI具有可比性。诊断GHD的最佳生长激素切点，FD - GST为1.0（敏感性92%，特异性100%），WB - GST为2.0 ng/mL（敏感性96%，特异性100%）。年龄与FD - GST期间的生长激素峰值呈负相关（r = -0.32，P = 0.04），但与WB - GST无关。诊断SAI的最佳皮质醇切点，FD - GST为8.8 μg/dL（敏感性92%，特异性100%），WB - GST为11.2 μg/dL（敏感性92%，特异性100%）。恶心是最常见的副作用，一名患者在FD - GST期间发生癫痫。
结论
GST使用FD - GST的生长激素切点1 ng/ml和WB - GST的2 ng/ml可正确分类GHD，因此使用3 ng/ml作为生长激素切点会将一些生长激素充足的成年人误分类。对于评估HPA轴，GST也可能是ITT的可接受替代方法，FD - GST的皮质醇切点为9 μg/dL，WB - GST为11 μg/dL。
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