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生长激素分泌型垂体腺瘤中奥曲肽与帕西瑞肽的体外直接比较

In Vitro Head-to-Head Comparison Between Octreotide and Pasireotide in GH-Secreting Pituitary Adenomas.

作者信息

Gatto Federico, Feelders Richard A, Franck Sanne E, van Koetsveld Peter M, Dogan Fadime, Kros Johan M, Neggers Sebastian J C M M, van der Lely Aart-Jan, Lamberts Steven W J, Ferone Diego, Hofland Leo J

机构信息

Division of Endocrinology, Department of Internal Medicine, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands.

Pituitary Center Rotterdam, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands.

出版信息

J Clin Endocrinol Metab. 2017 Jun 1;102(6):2009-2018. doi: 10.1210/jc.2017-00135.

Abstract

CONTEXT

First-generation somatostatin analogs (SSAs), such as octreotide (OCT), are the first line medical therapy for acromegaly. Pasireotide (PAS), a newly developed SSA, has shown promising results in the treatment of acromegaly.

OBJECTIVE

To compare the antisecretory effect of OCT and PAS in primary cultures of growth hormone (GH)-secreting pituitary adenomas (GH-omas). To correlate responses with the adenoma somatostatin receptor (SSTR) profile.

DESIGN

The effect of OCT and PAS on GH (and PRL) secretion was tested in 33 GH-oma cultures. SSTR expression was evaluated in adenoma samples.

SETTING AND PATIENTS

Patients with acromegaly referred to the Erasmus Medical Center (Rotterdam, The Netherlands).

INTERVENTIONS

OCT and PAS treatment for 72 hours (10 nM).

MAIN OUTCOME MEASURES

GH (and PRL) concentrations in cell culture media. SSTR expression in adenoma samples.

RESULTS

The overall effect of OCT (-36.8%) and PAS (-37.1%) on GH secretion was superimposable. We identified three adenoma groups: PAS+ (PAS more effective than OCT), n = 6; PAS = OCT, n = 22; and OCT+ (OCT more effective than PAS), n = 5. PAS+ adenomas showed lower somatostatin receptor subtype (sst)2 messenger RNA (mRNA) and sst2/sst5 mRNA ratio, compared with the other groups (P < 0.05). PAS inhibited PRL hypersecretion more than OCT (P < 0.01).

CONCLUSIONS

Overall, OCT and PAS equally reduced GH secretion in vitro. Adenomas with lower sst2 mRNA expression and lower sst2/sst5 mRNA ratio were better responders to PAS compared with OCT. SSTR evaluation in GH-omas may become a tool for tailored SSA treatment in acromegaly.

摘要

背景

第一代生长抑素类似物(SSA),如奥曲肽(OCT),是肢端肥大症的一线药物治疗方法。帕西瑞肽(PAS)是一种新开发的SSA,在肢端肥大症治疗中已显示出有前景的结果。

目的

比较奥曲肽和帕西瑞肽在分泌生长激素(GH)的垂体腺瘤(GH瘤)原代培养物中的抗分泌作用。将反应与腺瘤生长抑素受体(SSTR)谱相关联。

设计

在33种GH瘤培养物中测试奥曲肽和帕西瑞肽对GH(和PRL)分泌的作用。在腺瘤样本中评估SSTR表达。

地点和患者

转诊至伊拉斯谟医学中心(荷兰鹿特丹)的肢端肥大症患者。

干预措施

奥曲肽和帕西瑞肽治疗72小时(10 nM)。

主要观察指标

细胞培养基中的GH(和PRL)浓度。腺瘤样本中的SSTR表达。

结果

奥曲肽(-36.8%)和帕西瑞肽(-37.1%)对GH分泌的总体作用是叠加的。我们确定了三组腺瘤:帕西瑞肽敏感组(帕西瑞肽比奥曲肽更有效),n = 6;帕西瑞肽与奥曲肽疗效相同组,n = 22;奥曲肽敏感组(奥曲肽比帕西瑞肽更有效),n = 5。与其他组相比,帕西瑞肽敏感组腺瘤显示生长抑素受体亚型(sst)2信使核糖核酸(mRNA)和sst2/sst5 mRNA比值较低(P < 0.05)。帕西瑞肽比奥曲肽更能抑制PRL分泌过多(P < 0.01)。

结论

总体而言,奥曲肽和帕西瑞肽在体外同等程度地降低GH分泌。与奥曲肽相比,sst2 mRNA表达较低且sst2/sst5 mRNA比值较低的腺瘤对帕西瑞肽反应更好。GH瘤中的SSTR评估可能成为肢端肥大症中定制SSA治疗的一种工具。

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