Department of Oncology and Metabolism, The Medical School, University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK.
Sherwood Forest Hospitals, Nottinghamshire, NG17 4JL, UK.
Pituitary. 2018 Jun;21(3):247-255. doi: 10.1007/s11102-017-0853-3.
Nelson's syndrome is a challenging condition that can develop following bilateral adrenalectomy for Cushing's disease, with high circulating ACTH levels, pigmentation and an invasive pituitary tumor. There is no established medical therapy. The aim of the study was to assess the effects of pasireotide on plasma ACTH and tumor volume in Nelson's syndrome.
Open labeled multicenter longitudinal trial in three steps: (1) a placebo-controlled acute response test; (2) 1 month pasireotide 300-600 μg s.c. twice-daily; (3) 6 months pasireotide long-acting-release (LAR) 40-60 mg monthly.
Seven patients had s.c. treatment and 5 proceeded to LAR treatment. There was a significant reduction in morning plasma ACTH during treatment (mean ± SD; 1823 ± 1286 ng/l vs. 888.0 ± 812.8 ng/l during the s.c. phase vs. 829.0 ± 1171 ng/l during the LAR phase, p < 0.0001). Analysis of ACTH levels using a random intercept linear mixed-random effects longitudinal model showed that ACTH (before the morning dose of glucocorticoids) declined significantly by 26.1 ng/l per week during the 28-week of treatment (95% CI - 45.2 to - 7.1, p < 0.01). An acute response to a test dose predicted outcome in 4/5 patients. Overall, there was no significant change in tumor volumes (1.4 ± 0.9 vs. 1.3 ± 1.0, p = 0.86). Four patients withdrew during the study. Hyperglycemia occurred in 6 patients.
Pasireotide lowers plasma ACTH levels in patients with Nelson's syndrome. A longer period of treatment may be needed to assess the effects of pasireotide on tumor volume.
Clinical Trials.gov ID, NCT01617733.
纳尔逊综合征是一种具有挑战性的疾病，可在双侧肾上腺切除术治疗库欣病后发生，其特征为循环促肾上腺皮质激素（ACTH）水平升高、色素沉着和侵袭性垂体肿瘤。目前尚无既定的医学治疗方法。本研究旨在评估帕瑞肽对纳尔逊综合征患者血浆 ACTH 和肿瘤体积的影响。
本研究为三步开放标签的多中心纵向试验：（1）安慰剂对照的急性反应试验；（2）皮下注射帕瑞肽 300-600μg，每日两次，共 1 个月；（3）皮下注射帕瑞肽长效释放剂（LAR）40-60mg，每月 1 次，共 6 个月。
7 例患者接受了皮下治疗，5 例患者随后接受了 LAR 治疗。治疗期间清晨血浆 ACTH 水平显著下降（平均±标准差；皮下治疗期间为 1823±1286ng/l，与皮下治疗期间的 888.0±812.8ng/l相比，LAR 治疗期间为 829.0±1171ng/l，p<0.0001）。使用随机截距线性混合随机效应纵向模型分析 ACTH 水平显示，在 28 周的治疗期间，ACTH（在糖皮质激素的清晨剂量之前）每周下降 26.1ng/l（95%CI -45.2 至 -7.1，p<0.01）。单次剂量试验的急性反应可预测 5 例患者中的 4 例的结果。总体而言，肿瘤体积无显著变化（1.4±0.9 与 1.3±1.0，p=0.86）。4 例患者在研究期间退出。6 例患者出现高血糖。
帕瑞肽可降低纳尔逊综合征患者的血浆 ACTH 水平。可能需要更长的治疗时间来评估帕瑞肽对肿瘤体积的影响。
ClinicalTrials.gov 标识符，NCT01617733。
