Jackson S N, Fowler J, Howlett T A
Department of Diabetes and Endocrinology, Leicester Royal Infirmary, U.K.
Clin Endocrinol (Oxf). 1997 Jun;46(6):745-9. doi: 10.1046/j.1365-2265.1997.2491023.x.
Studies of the dopamine agonist cabergoline in the treatment of hyperprolactinaemia have shown it to be a potent, long-acting and well-tolerated. The older dopamine agonist, bromocriptine, has traditionally had a place in the medical management of acromegaly, but poor patient tolerance of the high doses required, the need for multiple daily administration and incomplete biochemical responses have limited its role. We therefore sought to investigate the effect of cabergoline on growth hormone (GH) secretion in acromegaly and to define the most appropriate dose for suppression of GH DESIGN AND MEASUREMENTS: Patients with active acromegaly (defined as most recent random GH > 5 mU/l) were identified from the departmental clinical information system. After informed consent was obtained, basal GH levels were estimated during a 5 point day curve at least 2 months after withdrawal of any existing medical therapy for acromegaly. The cabergoline dose was escalated on a monthly basis for 4 months with a repeat 5 point GH day curve at the highest dose, and 0900 and 0930 GH estimations at the intermediate dose increment stages. Serum IGF-1 and prolactin were estimated on each occasion. Biochemical remission was defined as serum GH < 5 mU/l.
Eleven acromegalics were investigated. Previous treatment included surgery (7), radiotherapy (5) and bromocriptine (5). Three patients had not received any previous treatment. All had random GH persistently > 5 mU/l prior to the study.
Ten patients completed the study. Of these, 7 showed a fall in the GH to < or = 33% and IGF-1 to < or = 67% of the basal value but only 2 achieved biochemical remission. All subjects showed maximum GH response at a dose of 0.5 mg daily of cabergoline. Four patients were unable to tolerate the maximum dose of 1 mg daily (nausea in one and nonspecific symptoms in three). The patient excluded from the analysis discontinued cabergoline and underwent surgery after 1 month because of worsening visual field defects.
Cabergoline may be a useful adjunct to the currently available treatment for acromegaly, but rarely achieves the goal of mean GH < 5 mU/l. The maximum suppression of GH is achieved within the dose range 1 mg twice weekly to 0.5 mg daily.
对多巴胺激动剂卡麦角林治疗高泌乳素血症的研究表明,它药效强大、作用持久且耐受性良好。传统上,较老的多巴胺激动剂溴隐亭在肢端肥大症的药物治疗中占有一席之地,但患者对所需高剂量耐受性差、需要每日多次给药以及生化反应不完全,限制了其作用。因此,我们试图研究卡麦角林对肢端肥大症患者生长激素(GH)分泌的影响,并确定抑制GH的最合适剂量。
从科室临床信息系统中识别出活动性肢端肥大症患者(定义为最近随机GH>5 mU/l)。在获得知情同意后,在停用任何现有的肢端肥大症治疗药物至少2个月后,通过5点日曲线估计基础GH水平。卡麦角林剂量每月递增,持续4个月,在最高剂量时重复5点GH日曲线,并在中间剂量递增阶段进行09:00和09:30的GH测定。每次都测定血清IGF-1和泌乳素。生化缓解定义为血清GH<5 mU/l。
对11例肢端肥大症患者进行了研究。既往治疗包括手术(7例)、放疗(5例)和溴隐亭(5例)。3例患者既往未接受任何治疗。所有患者在研究前随机GH持续>5 mU/l。
10例患者完成了研究。其中,7例患者的GH降至基础值的≤33%,IGF-1降至基础值的≤67%,但只有2例实现了生化缓解。所有受试者在卡麦角林每日剂量为0.5 mg时显示出最大GH反应。4例患者无法耐受每日1 mg 的最大剂量(1例出现恶心,3例出现非特异性症状)。因视野缺损恶化,被排除在分析之外的患者在1个月后停用卡麦角林并接受了手术。
卡麦角林可能是目前肢端肥大症治疗的有用辅助药物,但很少能达到平均GH<5 mU/l的目标。在每周两次1 mg至每日0.5 mg的剂量范围内可实现GH的最大抑制。