Corneli Ginevra, Di Somma Carolina, Baldelli Roberto, Rovere Silvia, Gasco Valentina, Croce Chiara Giulia, Grottoli Silvia, Maccario Mauro, Colao Annamaria, Lombardi Gaetano, Ghigo Ezio, Camanni Franco, Aimaretti Gianluca
Division of Endocrinology and Metabolic Diseases, Department of Internal Medicine, University of Turin, Italy.
Eur J Endocrinol. 2005 Aug;153(2):257-64. doi: 10.1530/eje.1.01967.
The diagnosis of growth hormone (GH) deficiency (GHD) in adults is based on a reduced peak GH response to provocative tests, such as the insulin tolerance test (ITT) and the GH-releasing hormone-arginine (GHRH-ARG) test. However, the cut-off limits of peak GH response in lean subjects are not reliable in obese patients; this is noteworthy since adult GHD is often associated with obesity. Aim of this study was to evaluate the diagnostic cut-off limits of peak GH response to the GHRH-ARG test in overweight and obese as well as in lean population.
The GH responses to the GHRH-ARG test were studied in 322 patients with organic hypothalamic-pituitary disease and in 318 control subjects. Patients were subdivided into two groups on the basis of the number of pituitary hormone deficits, except for GH deficiency: (a) patients with total pituitary hormone deficit (TPHD) and (b) patients without or with no more than two pituitary hormone deficits (PHD). Both patients and control subjects were divided into three subgroups according to body mass index (BMI): lean (BMI <25 kg/m(2)), overweight (BMI > or = 25 and <30 kg/m(2)) and obese (BMI > or =30 kg/m(2)). TPHD patients were assumed to be GH deficient, whereas PHD patients may include subjects with either normal or impaired GH secretion. The statistical analysis was carried out by the Receiver-Operating Characteristic curve analysis (Medcalc 7.2). The diagnostic cut-off points were calculated for lean, overweight and obese subjects to provide optimal separation of GH-deficient patients and control subjects according to two criteria: (1) a balance between high sensitivity and high specificity; (2) to provide the highest pair of sensitivity/specificity values for GH deficiency.
In the lean population the best pair of values, with highest sensitivity as 98.7% and highest specificity as 83.7%, was found using a peak GH cut-off point of 11.5 mug/l. In the overweight population the best pair of values, 96.7 and 75.5%, respectively, was found using a peak GH cut-off point of 8.0 mug/l. In the obese population the best pair of values, 93.5 and 78.3%, respectively, was found using a peak GH cut-off point of 4.2 mug/l. Applying the above mentioned cut-off points, among PHD patients we found that 80 subjects (72%) were GHD whereas 31 (28%) had normal GH secretion.
In conclusion the GHRH-ARG test is a reliable tool for the diagnosis of adult GH deficiency in lean, overweight and obese patients, provided that specific BMI-related cut-off limits are assumed.
成人生长激素（GH）缺乏症（GHD）的诊断基于对激发试验（如胰岛素耐量试验（ITT）和生长激素释放激素 - 精氨酸（GHRH - ARG）试验）的GH峰值反应降低。然而，瘦人GH峰值反应的临界值在肥胖患者中并不可靠；鉴于成人GHD常与肥胖相关，这一点值得注意。本研究的目的是评估超重和肥胖人群以及瘦人群体中GHRH - ARG试验的GH峰值反应的诊断临界值。
对322例患有器质性下丘脑 - 垂体疾病的患者和318例对照者进行了GHRH - ARG试验的GH反应研究。除GH缺乏外，根据垂体激素缺乏的数量将患者分为两组：（a）全垂体激素缺乏（TPHD）患者和（b）无或仅有不超过两种垂体激素缺乏（PHD）的患者。患者和对照者均根据体重指数（BMI）分为三个亚组：瘦（BMI <25 kg/m²）、超重（BMI≥25且<30 kg/m²）和肥胖（BMI≥30 kg/m²）。TPHD患者被认为是GH缺乏，而PHD患者可能包括GH分泌正常或受损的受试者。采用受试者操作特征曲线分析（Medcalc 7.2）进行统计分析。根据两个标准计算瘦、超重和肥胖受试者的诊断临界点，以实现GH缺乏患者和对照者的最佳区分：（1）高敏感性和高特异性之间的平衡；（2）为GH缺乏提供最高的敏感性/特异性值对。
在瘦人群体中，使用11.5 μg/l的GH峰值临界点发现最佳值对，敏感性最高为98.7%，特异性最高为83.7%。在超重人群中，使用8.0 μg/l的GH峰值临界点发现最佳值对，分别为96.7%和75.5%。在肥胖人群中，使用4.2 μg/l的GH峰值临界点发现最佳值对，分别为93.5%和78.3%。应用上述临界点，在PHD患者中，我们发现80名受试者（72%）为GHD，而31名（28%）的GH分泌正常。
总之，如果采用与BMI相关的特定临界值，GHRH - ARG试验是诊断瘦人、超重和肥胖成人GH缺乏症的可靠工具。
