■虽然有报道称使用[177Lu]Lu-DOTA-TATE治疗的嗜铬细胞瘤/副神经节瘤(PPGL)患者出现与治疗相关的内分泌干扰和儿茶酚胺激增,在治疗后即刻(48小时内)的这些异常的范围以前没有被评估过,可能被低估了.
■研究人群包括参加2期治疗生长抑素受体(SSTR)-2+不可手术/转移性嗜铬细胞瘤/副神经节瘤的患者(≥18岁)[177Lu]Lu-DOTA-TATE(每个周期7.4GBq,共1-4个周期)。激素测量[促肾上腺皮质激素(ACTH),皮质醇,促甲状腺激素(TSH),游离甲状腺素(FT4),卵泡刺激素(FSH),黄体生成素(LH),睾丸激素,雌二醇,生长激素,催乳素],儿茶酚胺,根据试验方案,每个周期在第1、2、3、30和60天获得间肾上腺素,并进行了回顾性分析。
■在27名患者中(年龄:54±12.7岁,48.1%的女性)接受荷尔蒙评估,低泌乳素血症(14.1%),FSH升高(13.1%),LH升高(12.5%)是所有4个周期中最常见的激素异常。关于纵向随访,i.ACTH显着减少,皮质醇没有相应的变化,Iftheparticularstandardsoftheparticularly,theparticularlytotheparticularlyofthebetweenthepurpose.TSH,和FT4,以及iii.[177Lu]Lu-DOTA-TATE第30天或之前的催乳素。促性腺激素轴和GH水平未观察到显着变化。第60天的所有激素水平与第1天值没有显着差异,这表明了这些变化的暂时性。然而,两名患者发展为临床,持续性内分泌疾病(原发性甲状腺功能减退症:n=1男性;绝经早期:n=1女性)。与第1天相比,去甲肾上腺素显著增加,多巴胺,在[177Lu]Lu-DOTA-TATE给药后24小时观察到去甲肾上腺素水平,并在48小时内达到峰值。
■[177Lu]Lu-DOTA-TATE治疗与SSTR2+内分泌组织辐射暴露引起的内分泌功能改变有关。然而,这些变化有时可能表现为临床上显著的内分泌疾病.因此,在[177Lu]Lu-DOTA-TATE治疗期间定期评估内分泌功能非常重要,尤其是有症状的患者。
■https://clinicaltrials.gov/ct2/show/NCT03206060?term=NCT03206060&draw=2&rank=1,标识符NCT03206060。
While there are reports of treatment-related endocrine disruptions and catecholamine surges in pheochromocytoma/paraganglioma (PPGL) patients treated with [177Lu]Lu-DOTA-TATE therapy, the spectrum of these abnormalities in the immediate post-treatment period (within 48 hours) has not been previously evaluated and is likely underestimated.
The study population included patients (≥18 years) enrolled in a phase 2 trial for treatment of somatostatin receptor (SSTR)-2+ inoperable/metastatic pheochromocytoma/paraganglioma with [177Lu]Lu-DOTA-TATE (7.4 GBq per cycle for 1 - 4 cycles). Hormonal measurements [adrenocorticotropic hormone (ACTH), cortisol, thyroid stimulating hormone (TSH), free thyroxine (FT4), follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, estradiol, growth hormone, prolactin], catecholamines, and metanephrines were obtained on days-1, 2, 3, 30, and 60 per cycle as per trial protocol, and were retrospectively analyzed.
Among the 27 patients (age: 54 ± 12.7 years, 48.1% females) who underwent hormonal evaluation, hypoprolactinemia (14.1%), elevated FSH (13.1%), and elevated LH (12.5%) were the most frequent hormonal abnormalities across all 4 cycles combined. On longitudinal follow-up, significant reductions were noted in i. ACTH without corresponding changes in cortisol, ii. TSH, and FT4, and iii. prolactin at or before day-30 of [177Lu]Lu-DOTA-TATE. No significant changes were observed in the gonadotropic axis and GH levels. Levels of all hormones on day-60 were not significantly different from day-1 values, suggesting the transient nature of these changes. However, two patients developed clinical, persistent endocrinopathies (primary hypothyroidism: n=1 male; early menopause: n=1 female). Compared to day-1, a significant % increase in norepinephrine, dopamine, and normetanephrine levels were noted at 24 hours following [177Lu]Lu-DOTA-TATE dose and peaked within 48 hours.
[177Lu]Lu-DOTA-TATE therapy is associated with alterations in endocrine function likely from radiation exposure to SSTR2+ endocrine tissues. However, these changes may sometimes manifest as clinically significant endocrinopathies. It is therefore important to periodically assess endocrine function during [177Lu]Lu-DOTA-TATE therapy, especially among symptomatic patients.
https://clinicaltrials.gov/ct2/show/NCT03206060?term=NCT03206060&draw=2&rank=1, identifier NCT03206060.