Beentjes J A, Tjeerdsma G, Sluiter W J, Dullaart R P
Department of Endocrinology, University Hospital Groningen, The Netherlands.
Clin Endocrinol (Oxf). 1996 Oct;45(4):391-8. doi: 10.1046/j.1365-2265.1996.8210831.x.
The GH responses to the insulin tolerance test (ITT) and growth hormone-releasing hormone (GHRH) may yield different results in patients with pituitary lesions. The GH responses to these stimuli were compared in patients with untreated non-functioning pituitary macroadenomas, who represent an important cause of GH deficiency.
Analysis of peak GH to ITT and to 100 micrograms GHRH in relation to an elevated PRL level (> 200 mIU/l for males and > 600 mIU/l for females) as an indication of hypothalamic-pituitary dysregulation, as well as in relation to other anterior pituitary hormone deficiencies. A peak GH < 5 micrograms/l in either test indicated GH deficiency.
Twenty females and 14 males (median age 52 (23-77) years) evaluated preoperatively in a university hospital setting.
In the whole group the median peak GH to GHRH (3.6 (0.9-26.3) micrograms/l) was higher than to ITT (1.6 (0.2-7.8) micrograms/l, P < 0.001). This difference was seen only in 19 patients with concomitant hyperprolactinaemia (P < 0.001). When hyperprolactinaemia was present, an insufficient GH peak was demonstrated by ITT in 16 cases and by GHRH stimulation in 7 cases (P < 0.01). The frequency of an insufficient GH peak by ITT (13 cases) and by GHRH (14 cases) was similar in the normoprolactinaemic patients. In addition, 9 of 10 patients with an impaired response to ITT and a normal response to GHRH were hyperprolactinaemic compared to 7 of 19 patients with GH deficiency as assessed by both stimuli (P < 0.02). Peak GH to ITT was lower in 24 patients with, compared to 10 patients without, other hormonal deficiencies (1.4 (0.2-5.6) vs 3.0 (1.0-7.8) micrograms/l, P < 0.02), but was not related to elevated PRL. In contrast, GHRH-stimulated GH was higher in hyperprolactinaemic than in normoprolactinaemic patients (5.9 (1.6-26.3) vs 2.9 (0.9-5.4) micrograms/l, P < 0.001) and was not related to the presence of other pituitary hormone deficiencies. Analysis of covariance confirmed that peak GH to ITT was negatively associated with the presence of other pituitary hormone deficiencies (P < 0.01), whereas peak GH to GHRH was positively related to an elevated PRL level (P < 0.02). Basal GH was positively correlated with PRL (R(s) = 0.36, P < 0.05).
This study demonstrates that ITT and GHRH tests cannot be used interchangeably in diagnosing GH deficiency in patients with non-functioning pituitary macroadenoma and hyperprolactinaemia. If the ITT is considered to be the reference test, GH deficiency as assessed by GHRH can be missed in patients with hyperprolactinaemia. This disparity is probably due to a different mechanism of action of these stimuli. Hyperprolactinaemia may be associated with a diminished somatostatin tone, leading to a higher basal and GHRH-stimulated GH, without having an effect on peak GH to ITT.
生长激素（GH）对胰岛素耐量试验（ITT）和生长激素释放激素（GHRH）的反应在垂体病变患者中可能产生不同结果。在未治疗的无功能垂体大腺瘤患者中比较了GH对这些刺激的反应，此类患者是GH缺乏的一个重要原因。
分析ITT和100微克GHRH刺激后的GH峰值与催乳素（PRL）水平升高（男性>200 mIU/L，女性>600 mIU/L）的关系，以此作为下丘脑-垂体调节异常的指标，同时分析与其他垂体前叶激素缺乏的关系。任何一项试验中GH峰值<5微克/L表明存在GH缺乏。
20名女性和14名男性（中位年龄52（23 - 77）岁），于大学医院术前进行评估。
在整个研究组中，GHRH刺激后的GH峰值中位数（3.6（0.9 - 26.3）微克/L）高于ITT刺激后的GH峰值中位数（1.6（0.2 - 7.8）微克/L，P<0.001）。这种差异仅在19例伴有高催乳素血症的患者中可见（P<0.001）。当存在高催乳素血症时，ITT显示16例患者GH峰值不足，GHRH刺激显示7例患者GH峰值不足（P<0.01）。在催乳素水平正常的患者中，ITT显示GH峰值不足的频率（13例）与GHRH显示GH峰值不足的频率（14例）相似。此外，10例对ITT反应受损但对GHRH反应正常的患者中有9例存在高催乳素血症，相比之下，两种刺激评估均显示GH缺乏的19例患者中有7例存在高催乳素血症（P<0.02）。与10例无其他激素缺乏的患者相比，24例有其他激素缺乏的患者ITT刺激后的GH峰值更低（1.4（0.2 - 5.6）微克/L对3.0（1.0 - 7.8）微克/L，P<0.02），但与PRL升高无关。相比之下，高催乳素血症患者中GHRH刺激后的GH高于催乳素水平正常的患者（5.9（1.6 - 26.3）微克/L对2.9（0.9 - 5.4）微克/L，P<0.001），且与其他垂体激素缺乏的存在无关。协方差分析证实，ITT刺激后的GH峰值与其他垂体激素缺乏的存在呈负相关（P<0.01），而GHRH刺激后的GH峰值与PRL水平升高呈正相关（P<0.02）。基础GH与PRL呈正相关（R(s)=0.36，P<0.05）。
本研究表明，在诊断无功能垂体大腺瘤和高催乳素血症患者的GH缺乏时，ITT和GHRH试验不能相互替代使用。如果将ITT视为参考试验，高催乳素血症患者中通过GHRH评估的GH缺乏可能会被漏诊。这种差异可能是由于这些刺激的作用机制不同。高催乳素血症可能与生长抑素张力降低有关，导致基础和GHRH刺激后的GH升高，而对ITT刺激后的GH峰值无影响。
