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培维索孟预激胰高血糖素刺激试验在评估疑似生长激素缺乏症成人的生长激素储备及生长激素/胰岛素样生长因子动力学中的应用

Pegvisomant-primed glucagon stimulation test in assessing GH reserve and GH/IGF kinetics in adults suspected of GH deficiency.

作者信息

Yuen Kevin C J, Frystyk Jan, Rhoads Sharon A, Bidlingmaier Martin

出版信息

Pituitary. 2016 Feb;19(1):65-74. doi: 10.1007/s11102-015-0688-8.

Abstract

PURPOSE

The accuracy of the glucagon stimulation test(GST) in diagnosing adult GH deficiency (GHD) has recently been questioned. Because pegvisomant (PegV)increases endogenous GH secretion, we hypothesized that priming PegV to the GST (PegV-GST) 72 h beforehand would improve the diagnostic accuracy of this test. This pilot study aimed to prospectively compare PegV-GST to two other diagnostic tests for adult GHD.

METHODS

Adults suspected of GHD underwent PegVGST,GST and insulin tolerance test (ITT) in random order.Growth hormone levels (measured by a PegV insensitive assay) during PegV-GST, GST and ITT were compared,and acute effects of PegV on GH/IGF kinetics were assessed.

RESULTS

Ten subjects with hypothalamic-pituitary disease and 1–4 pituitary hormone deficiencies were studied. Basal and peak GH levels with the PegV-GST were comparable to those of the GST and ITT. The five subjects that failed the GST and ITT were the same subjects that failed the PegVGST,using the peak GH cut point of<3 ng/mL for this test. After PegV priming, basal GH and GH binding protein(GHBP) increased (both P<0.01) and total IGF-I and bioactive IGF decreased (both P<0.05), whereas IGF-II and IGFBPs -1, -2 and -3 were unchanged compared to pre-PegV priming. Serum PegV levels correlated positively with basal GH, peak GH, IGFBP-1 and IGFBP-2 levels, and negatively with D bioactive IGF and DGHBP (all P<0.05).

CONCLUSION

Single dose PegV administration in adults suspected of GHD increased basal GH and GHBP, with concomitant rapid fall in IGF-I levels and bioactive IGF. PegV priming did not appear to improve the diagnostic accuracy of the GST. Further studies involving larger subject numbers are needed to verify the clinical utility of PegV-GST in evaluating adult GHD.

摘要

目的

近期,胰高血糖素刺激试验(GST)在诊断成人生长激素缺乏症(GHD)中的准确性受到质疑。由于培维索孟(PegV)可增加内源性生长激素分泌,我们推测提前72小时将培维索孟用于GST(PegV-GST)可提高该试验的诊断准确性。这项初步研究旨在前瞻性地比较PegV-GST与其他两种成人GHD诊断试验。

方法

疑似GHD的成年人按随机顺序接受PegV-GST、GST和胰岛素耐量试验(ITT)。比较PegV-GST、GST和ITT期间的生长激素水平(通过对PegV不敏感的检测方法测量),并评估PegV对生长激素/胰岛素样生长因子动力学的急性影响。

结果

研究了10名下丘脑-垂体疾病患者和1至4种垂体激素缺乏患者。PegV-GST的基础和峰值生长激素水平与GST和ITT相当。使用该试验峰值生长激素切点<3 ng/mL,5名未通过GST和ITT的受试者同样未通过PegV-GST。培维索孟预处理后,基础生长激素和生长激素结合蛋白(GHBP)增加(均P<0.01),总胰岛素样生长因子-I和生物活性胰岛素样生长因子降低(均P<0.05),而与培维索孟预处理前相比,胰岛素样生长因子-II和胰岛素样生长因子结合蛋白-1、-2和-3未发生变化。血清培维索孟水平与基础生长激素、峰值生长激素、胰岛素样生长因子结合蛋白-1和胰岛素样生长因子结合蛋白-2水平呈正相关,与生物活性胰岛素样生长因子和生长激素结合蛋白降低呈负相关(均P<0.05)。

结论

在疑似GHD的成年人中单次给予培维索孟可增加基础生长激素和生长激素结合蛋白,同时胰岛素样生长因子-I水平和生物活性胰岛素样生长因子迅速下降。培维索孟预处理似乎并未提高GST的诊断准确性。需要进行涉及更多受试者的进一步研究,以验证PegV-GST在评估成人GHD中的临床实用性。

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