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
Department of Biology, University of Padova, Via Ugo Bassi 58/B, 35128, Padua, Italy.
Department of Medicine (DIMED), University of Padova, Padua, Italy.
J Endocrinol Invest. 2025 May;48(5):1173-1183. doi: 10.1007/s40618-025-02534-3. Epub 2025 Jan 22.
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.
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.
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).
The GH-Par does not predict the response to pasireotide in acromegaly but can predict a worse metabolic profile.
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。
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。
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）。
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。
