生长激素刺激试验在诊断矮小儿童中的临床应用局限性。

Limitations of clinical utility of growth hormone stimulating tests in diagnosing children with short stature.

作者信息

Hilczer Maciej, Smyczynska Joanna, Lewinski Andrzej

机构信息

Department of Endocrinology and Metabolic Diseases, Medical University of Lodz, Polish Mother's Memorial Hospital - Research Institute, Lodz, Poland.

出版信息

Endocr Regul. 2006 Sep;40(3):69-75.

PMID:17100548

Abstract

OBJECTIVE

The diagnosis of growth hormone (GH) deficiency (GHD) is routinely based on the results of two stimulating tests performed with different stimuli. Arbitrarily established, equal cutoff levels for the tests with different pharmacological stimuli, as well as a relatively high incidence of falsely decreased (FD) response in the tests have been reported. Falsely decreased GH response in one of the two performed tests does not exclude FD response in the second one, so, it seems very important to assess the incidence of FD response in both GH stimulating tests.

SUBJECTS AND METHODS

The analysis comprised the results of two GH stimulating tests (the 1st one with clonidine, the 2nd one with either insulin or glucagon) performed in 780 short children.

RESULTS

The mean GH peak in the test with clonidine was significantly higher than that in both other tests (p<0.01). The rate of decreased GH secretion was 48.7 % in the test with clonidine, 80.5 % in the test with insulin and 81.5 % in the test with glucagon. Similar frequency of normal and subnormal test results was obtained for the cut-off value for the tests with insulin and with glucagon at the level of 6.4 ng/ml. The correlation between the results of the two tests as performed in particular patients was weak (r=0.27; p<0.05). Following cases of test results were found: 1. both results normal (1st NT, 2nd NT) in 117 patients (15.0 %), 2. 1st result normal, while the 2nd one falsely decreased (1st NT, 2nd FD) in 283 (36.3 %), 3. reverse situation (1st FD, 2nd NT) in 62 (7.9 %), 4. both results decreased in 318 (40.8 %), either truly (1st TD, 2nd TD) or falsely (1st FD, 2nd FD) - with unknown incidence. The following incidences (probabilities - P) result from the above data: A. P(1st NT, 2nd NT) = P(1st NT) intersection P(2nd NT) = 0.150; B. P(1st NT, 2nd FD) = P(1st NT) intersection P(2nd FD) = 0.363; C. P(1st FD, 2nd NT) = P(1st FD) intersection P(2nd NT) = 0.079. The expression (B intersection C)/A was calculated by transforming the right side of the equations: (B x C)/A = 0.192. Thus, 19.2 %, out of all 780 patients, i.e., 150 children (47.2 % of 318 patients, assessed as GH-deficient), could have both test results FD.

CONCLUSIONS

The observed differences in GH response to particular pharmacological stimuli, as well as the high incidence of falsely decreased GH response in the two stimulating tests, should be taken into account in qualifying short children to GH therapy.

摘要

目的

生长激素（GH）缺乏症（GHD）的诊断通常基于采用不同刺激物进行的两项刺激试验的结果。据报道，针对不同药理刺激物的试验，其截断值是任意设定的，且试验中假降低（FD）反应的发生率相对较高。在两项进行的试验中，若其中一项试验的GH反应假降低，并不能排除另一项试验中出现FD反应的可能性，因此，评估两项GH刺激试验中FD反应的发生率似乎非常重要。

对象与方法

分析包括对780名身材矮小儿童进行的两项GH刺激试验（第一项用可乐定，第二项用胰岛素或胰高血糖素）的结果。

结果

可乐定试验中的平均GH峰值显著高于其他两项试验（p<0.01）。可乐定试验中GH分泌降低的发生率为48.7%，胰岛素试验中为80.5%，胰高血糖素试验中为81.5%。胰岛素试验和胰高血糖素试验在截断值为6.4 ng/ml时，获得了相似的正常和低于正常试验结果频率。特定患者进行的两项试验结果之间的相关性较弱（r=0.27；p<0.05）。发现了以下几种试验结果情况：1. 两项结果均正常（第一次正常，第二次正常）的有117例患者（15.0%）；2. 第一次结果正常，而第二次结果假降低（第一次正常，第二次FD）的有283例（36.3%）；3. 相反情况（第一次FD，第二次正常）的有62例（7.9%）；4.两项结果均降低的有318例（40.8%），可能是真降低（第一次真降低，第二次真降低）或假降低（第一次FD，第二次FD），其发生率未知。根据上述数据得出以下发生率（概率 - P）：A. P（第一次正常，第二次正常）= P（第一次正常）与P（第二次正常）的交集 = 0.150；B. P（第一次正常，第二次FD）= P（第一次正常）与P（第二次FD）的交集 = 0.363；C. P（第一次FD，第二次正常）= P（第一次FD）与P（第二次正常）的交集 = 0.079。通过对方程右侧进行变换计算表达式（B与C的交集）/A：（B×C）/A = 0.192。因此，在所有780例患者中，有19.2%，即150名儿童（在评估为GH缺乏的318例患者中占47.2%）可能两项试验结果均为FD。