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口服葡萄糖耐量试验(OGTT)中矛盾的生长激素(GH)反应不能预测帕西瑞肽的疗效,但对葡萄糖代谢有影响。

The paradoxical GH response at OGTT does not predict Pasireotide efficacy but matters for glucose metabolism.

作者信息

Occhi G, Voltan G, Chiloiro S, Bianchi A, Maffei P, Dassie F, Mantovani G, Del Sindaco G, Ferone D, Gatto F, Losa M, Cannavò S, Scaroni C, Ceccato F

机构信息

Department of Biology, University of Padova, Via Ugo Bassi 58/B, 35128, Padua, Italy.

Department of Medicine (DIMED), University of Padova, Padua, Italy.

出版信息

J Endocrinol Invest. 2025 May;48(5):1173-1183. doi: 10.1007/s40618-025-02534-3. Epub 2025 Jan 22.

Abstract

PURPOSE

A paradoxical increase in GH after oral glucose load (GH-Par) characterizes about one-third of acromegaly patients and is associated with a better response to first-generation somatostatin receptor ligands (fg-SRLs). Pasireotide is typically considered as a second-/third-line treatment. Here, we investigated the predictive role of GH-Par in pasireotide response and adverse event development.

METHODS

we collected a multicenter Italian retrospective cohort of 59 patients treated with pasireotide for at least 3 months, all having GH profile from OGTT. IGF-1 normalization or at least 30% reduction at the last follow-up visit defined a responder patient.

RESULTS

Considering the entire cohort, median IGF-1 levels before pasireotide (available in 57 patients) were 1.38 times the upper limit of normal (ULN) in patients with large (median size 18 mm) and invasive (82%) adenomas after failure of fg-SRL treatment. After a 40-month median treatment, pasireotide effectively reduced IGF-1 ULN levels in 41 patients, 37 of whom achieving normalization, and 4 with a ≥ 30% reduction. Thirteen patients were classified as GH-Par. The median pasireotide duration, dosage, and efficacy (9/12 responder in the GH-Par group and 32/45 in the GH-NPar) were similar between groups. However, the occurrence of new-onset or worsening glucose metabolism alterations (GMAs) after pasireotide was more frequent in GH-NPar (from 37 to 80%; p < 0.001) compared to GH-Par patients (from 69 to 76%), likely due to the higher prevalence of pre-existing GMAs in the GH-Par group before starting pasireotide (p = 0.038).

CONCLUSIONS

The GH-Par does not predict the response to pasireotide in acromegaly but can predict a worse metabolic profile.

摘要

目的

口服葡萄糖负荷后生长激素(GH)出现反常升高(GH-Par)的情况在约三分之一的肢端肥大症患者中存在,且与对第一代生长抑素受体配体(fg-SRLs)的较好反应相关。帕西瑞肽通常被视为二线/三线治疗药物。在此,我们研究了GH-Par在帕西瑞肽反应及不良事件发生中的预测作用。

方法

我们收集了一个意大利多中心回顾性队列,其中59例患者接受帕西瑞肽治疗至少3个月,所有患者均有口服葡萄糖耐量试验(OGTT)的GH谱。在最后一次随访时,胰岛素样生长因子-1(IGF-1)正常化或至少降低30%定义为有反应的患者。

结果

在整个队列中,帕西瑞肽治疗前(57例患者数据可用),fg-SRL治疗失败后,大腺瘤(中位大小18mm)且侵袭性腺瘤(82%)患者的IGF-1水平中位数是正常上限(ULN)的1.38倍。经过中位40个月的治疗,帕西瑞肽有效降低了41例患者的IGF-1 ULN水平,其中37例实现正常化,4例降低≥30%。13例患者被归类为GH-Par。两组之间帕西瑞肽的中位治疗持续时间、剂量和疗效(GH-Par组9/12例有反应,GH-NPar组32/45例有反应)相似。然而,与GH-Par患者(从69%至76%)相比,GH-NPar患者在帕西瑞肽治疗后新发或恶化的糖代谢改变(GMA)更为频繁(从37%至80%;p<0.001),这可能是由于GH-Par组在开始帕西瑞肽治疗前已有GMA的患病率较高(p=0.038)。

结论

GH-Par不能预测肢端肥大症患者对帕西瑞肽的反应,但可预测较差的代谢状况。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1c3/12049373/dbb2fef57f1f/40618_2025_2534_Fig1_HTML.jpg

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