生长激素（GH）受体拮抗剂培维索孟治疗对长期高剂量生长抑素类似物治疗耐药的肢端肥大症患者12个月的疗效：对胰岛素样生长因子-I（IGF-I）水平、肿瘤体积、高血压和糖耐量的影响
Efficacy of 12-month treatment with the GH receptor antagonist pegvisomant in patients with acromegaly resistant to long-term, high-dose somatostatin analog treatment: effect on IGF-I levels, tumor mass, hypertension and glucose tolerance.
作者信息
Colao Annamaria, Pivonello Rosario, Auriemma Renata S, De Martino Maria Cristina, Bidlingmaier Martin, Briganti Francesco, Tortora Fabio, Burman Pia, Kourides Ione A, Strasburger Christian J, Lombardi Gaetano
机构信息
Department of Molecular and Clinical Endocrinology and Oncology, Section of Endocrinology, Federico II University of Naples, Italy.
出版信息
Eur J Endocrinol. 2006 Mar;154(3):467-77. doi: 10.1530/eje.1.02112.
OBJECTIVE
We aimed to investigate the efficacy of pegvisomant in patients with acromegaly resistant to long-term (> or = 24-month), high-dose treatment with octreotide-LAR (40 mg/month) or lanreotide (120 mg/month).
DESIGN
This was an open, prospective study.
SUBJECTS AND METHODS
We studied 16 patients with acromegaly (nine women; aged 28-61 years). The main outcome measures were IGF-I levels, blood pressure, glucose tolerance and safety (liver function and tumor size). Pegvisomant was given at doses of 10-40 mg s.c. daily. Dose titration was performed every month by IGF-I assay.
RESULTS
Three patients spontaneously stopped pegvisomant treatment after 6-9 months because of poor compliance; from the measurement of serum pegvisomant, another patient was found not to inject herself properly. After 6 months, IGF-I levels decreased by 63 +/- 19% (767.8 +/- 152.9 vs 299.8 +/- 162.9 microg/l, P < 0.0001, t-test); serum IGF-I levels normalized in 57%. After 12 months, IGF-I levels normalized in nine (75%) patients and were reduced by over 50% in another three (25%). The mean tumor volume remained stable during the study (1198 +/- 1234 vs 1196 +/- 1351 mm(3), P = 0.37): it did not change ( +/- 25% vs basal) in nine patients, increased by 39.4% and 40.8% in two and decreased by 30.8-46.5% in four. The total/high-density lipoprotein (HDL):cholesterol ratio (from 4.4 +/- 1.0 to 3.7 +/- 0.6, P = 0.0012), glucose levels (from 5.6 +/- 1.2 to 4.4 +/- 1.4 mmol/l, P = 0.026), insulin levels (from 12.4 +/- 6.7 to 8.1 +/- 3.0 mUl/l, P = 0.0023) and homeostasis model assessment (HOMA) index (from 3.4 +/- 2.1 to 1.9 +/- 1.0, P = 0.0017) decreased.
CONCLUSIONS
Treatment for 12 months with pegvisomant normalized IGF-I levels, and improved cardiovascular risk parameters and insulin sensitivity in patients with acromegaly resistant to long-term, high-dose treatment with somatostatin analogs. The tolerance of treatment was good.
目的
我们旨在研究培维索孟对长期（≥24个月）接受高剂量奥曲肽长效释放剂（40mg/月）或兰瑞肽（120mg/月）治疗仍耐药的肢端肥大症患者的疗效。
设计
这是一项开放性前瞻性研究。
研究对象与方法
我们研究了16例肢端肥大症患者（9例女性；年龄28 - 61岁）。主要观察指标为胰岛素样生长因子-I（IGF-I）水平、血压、糖耐量及安全性（肝功能和肿瘤大小）。培维索孟皮下注射，剂量为每日10 - 40mg。每月通过检测IGF-I进行剂量滴定。
结果
3例患者因依从性差在6 - 9个月后自行停止培维索孟治疗；通过检测血清培维索孟发现，另1例患者未正确注射。6个月后，IGF-I水平下降了63±19%（767.8±152.9 vs 299.8±162.9μg/L，P < 0.0001，t检验）；57%的患者血清IGF-I水平恢复正常。12个月后，9例（75%）患者的IGF-I水平恢复正常，另外3例（25%）患者的IGF-I水平降低超过50%。研究期间平均肿瘤体积保持稳定（1198±1234 vs 1196±133351mm³，P = 0.37）：9例患者肿瘤体积未变化（与基线相比变化±25%），2例患者肿瘤体积分别增加39.4%和40.8%，4例患者肿瘤体积分别下降30.8% - 46.5%。总胆固醇/高密度脂蛋白（HDL）胆固醇比值（从4.4±1.0降至3.7±0.6，P = 0.0012）、血糖水平（从5.6±1.2降至4.4±1.4mmol/L，P = 0.026）、胰岛素水平（从12.4±6.7降至8.1±3.0mU/L，P = 0.0023）及稳态模型评估（HOMA）指数（从3.4±2.1降至1.9±1.0，P = 0.0017）均下降。
结论
对于长期接受高剂量生长抑素类似物治疗仍耐药的肢端肥大症患者，使用培维索孟治疗12个月可使IGF-I水平恢复正常，并改善心血管风险参数及胰岛素敏感性。治疗耐受性良好。
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