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用于评估经成功治疗的肢端肥大症患者生长激素(GH)状态的胃饥饿素检测

Ghrelin test for the assessment of GH status in successfully treated patients with acromegaly.

作者信息

Pekic S, Doknic M, Miljic D, Joksimovic M, Glodic J, Djurovic M, Dieguez C, Casanueva F, Popovic V

机构信息

Institute of Endocrinology, Diabetes and Metabolism, University Clincal Centre, Belgrade, Serbia.

出版信息

Eur J Endocrinol. 2006 May;154(5):659-66. doi: 10.1530/eje.1.02148.

Abstract

OBJECTIVE

Posttreatment assessment of disease activity and definition of cure of acromegaly, using measurement of GH secretion, remains problematic. Furthermore, with our efforts to achieve tight biochemical control of the disease it is foreseeable that a proportion of patients may be rendered GH deficient, thus requiring testing for GH deficiency. The aim of our study was to evaluate residual GH secretion in cured patients with acromegaly.

DESIGN AND METHODS

At baseline, circulating GH, IGF-I, IGFBP-3, leptin and lipid (cholesterol and tri-glycerides) levels were measured in 33 acromegalic patients nine years after treatment with surgery of whom 6 were additionally irradiated. Two tests were performed: the GH suppression test--oral glucose tolerance test (OGTT) and the GH provocation test--ghrelin test (1 microg/kg i.v. bolus) and the results were compared with 11 age- and sex-matched control subjects.

RESULTS

According to the consensus criteria (normal IGF-I levels and post-OGTT GH nadir <1 microg/l), 21 treated acromegalic patients were cured, 6 had discordant IGF-I and GH nadir values during OGTT, while 6 had persistent acromegaly. After the GH provocative test with ghrelin (cut-off for severe GH deficiency is GH <3 microg/l), we detected 9 severely GH deficient patients (GHD) among 21 cured acromegalic patients. Mean GH peak (+/-s.e.m.) response to the ghrelin test in GHD acromegalics was significantly lower compared with acromegalics with sufficient GH secretory capacity and control subjects (1.2 +/- 0.2 microg/l vs 20.1 +/- 2.4 microg/l vs 31.1 +/- 2.5 microg/l respectively, P<0.0001). Mean IGF-I and IGFBP-3 levels were not different between GHD and GH-sufficient cured acromegalics. Leptin levels and body mass index (BMI) were significantly higher in GHD male acromegalics compared with GH-sufficient male acromegalics. GHD female acromegalics tended to have higher BMIs while leptin levels were not different.

CONCLUSIONS

The assessment of residual GH secretory capacity by the GH provocation test is necessary in the long-term follow-up of successfully treated acromegalics since a large proportion of these patients are rendered GH deficient.

摘要

目的

利用生长激素(GH)分泌测量对肢端肥大症的疾病活动进行治疗后评估以及治愈的定义仍然存在问题。此外,随着我们努力实现对该疾病的严格生化控制,可以预见一部分患者可能会出现GH缺乏,因此需要进行GH缺乏检测。我们研究的目的是评估治愈的肢端肥大症患者的残余GH分泌情况。

设计与方法

在基线时,对33例接受手术治疗9年的肢端肥大症患者测量循环中的GH、胰岛素样生长因子-I(IGF-I)、胰岛素样生长因子结合蛋白-3(IGFBP-3)、瘦素和血脂(胆固醇和甘油三酯)水平,其中6例还接受了放疗。进行了两项测试:GH抑制试验——口服葡萄糖耐量试验(OGTT)和GH激发试验——胃饥饿素试验(静脉推注1微克/千克),并将结果与11名年龄和性别匹配的对照受试者进行比较。

结果

根据共识标准(IGF-I水平正常且OGTT后GH最低点<1微克/升),21例接受治疗的肢端肥大症患者治愈,6例在OGTT期间IGF-I和GH最低点值不一致,而6例仍患有持续性肢端肥大症。在进行胃饥饿素GH激发试验后(严重GH缺乏的临界值为GH<3微克/升),我们在21例治愈的肢端肥大症患者中检测到9例严重GH缺乏患者(GHD)。GHD肢端肥大症患者对胃饥饿素试验的平均GH峰值(±标准误)反应与具有足够GH分泌能力的肢端肥大症患者和对照受试者相比显著降低(分别为1.2±0.2微克/升、20.1±2.4微克/升和31.1±2.5微克/升,P<0.0001)。GHD和GH充足的治愈肢端肥大症患者之间的平均IGF-I和IGFBP-3水平没有差异。GHD男性肢端肥大症患者的瘦素水平和体重指数(BMI)显著高于GH充足的男性肢端肥大症患者。GHD女性肢端肥大症患者的BMI往往较高,而瘦素水平没有差异。

结论

在成功治疗的肢端肥大症患者的长期随访中进行GH激发试验以评估残余GH分泌能力是必要的,因为这些患者中有很大一部分会出现GH缺乏。

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