Verhelst J, Abs R, Maiter D, van den Bruel A, Vandeweghe M, Velkeniers B, Mockel J, Lamberigts G, Petrossians P, Coremans P, Mahler C, Stevenaert A, Verlooy J, Raftopoulos C, Beckers A
Department of Endocrinology, Middelheim Ziekenhuis, Antwerpen, Belgium.
J Clin Endocrinol Metab. 1999 Jul;84(7):2518-22. doi: 10.1210/jcem.84.7.5810.
Cabergoline is a new long-acting dopamine agonist that is very effective and well tolerated in patients with pathological hyperprolactinemia. The aim of this study was to examine, in a very large number of hyperprolactinemic patients, the ability to normalize PRL levels with cabergoline, to determine the effective dose and tolerance, and to assess the effect on clinical symptoms, tumor shrinkage, and visual field abnormalities. We also evaluated the effects of cabergoline in a large subgroup of patients with bromocriptine intolerance or -resistance. We retrospectively reviewed the files of 455 patients (102 males and 353 females) with pathological hyperprolactinemia treated with cabergoline in 9 Belgian centers. Among these patients, 41% had a microadenoma; 42%, a macroadenoma; 16%, idiopathic hyperprolactinemia; and 1%, an empty sella. The median pretreatment serum PRL level was 124 microg/L (range, 16-26,250 microg/L). A subgroup of 292 patients had previously been treated with bromocriptine, of which 140 showed bromocriptine intolerance and 58 showed bromocriptine resistance. Treatment with cabergoline normalized serum PRL levels in 86% of all patients: in 92% of 244 patients with idiopathic hyperprolactinemia or a microprolactinoma and in 77% of 181 macroadenomas. Pretreatment visual field abnormalities normalized in 70% of patients, and tumor shrinkage was seen in 67% of cases. Side effects were noted in 13% of patients, but only 3.9% discontinued therapy because of side effects. The median dose of cabergoline at the start of therapy was 1.0 mg/week but could be reduced to 0.5 mg/week once control was achieved. Patients with a macroprolactinoma needed a higher median cabergoline dose, compared with those with idiopathic hyperprolactinemia or a microprolactinoma: 1.0 mg/week vs. 0.5 mg/week, although a large overlap existed between these groups. Twenty-seven women treated with cabergoline became pregnant, and 25 delivered a healthy child. One patient had an intended abortion and another a miscarriage. In the patients with bromocriptine intolerance, normalization of PRL was reached in 84% of cases, whereas in the bromocriptine-resistant patients, PRL could be normalized in 70%. We confirmed, in a large-scale retrospective study, the high efficacy and tolerability of cabergoline in the treatment of pathological hyperprolactinemia, leaving few patients with unacceptable side effects or inadequate clinical response. Patients with idiopathic hyperprolactinemia or a microprolactinoma, on average, needed only half the dose of cabergoline as those with macroprolactinomas and have a higher chance of obtaining PRL normalization. Cabergoline also normalized PRL in the majority of patients with known bromocriptine intolerance or -resistance. Once PRL secretion was adequately controlled, the dose of cabergoline could often be significantly decreased, which further reduced costs of therapy.
卡麦角林是一种新型长效多巴胺激动剂,对病理性高泌乳素血症患者疗效显著且耐受性良好。本研究旨在考察大量高泌乳素血症患者使用卡麦角林使泌乳素(PRL)水平恢复正常的能力,确定有效剂量和耐受性,并评估其对临床症状、肿瘤缩小及视野异常的影响。我们还评估了卡麦角林在一大组对溴隐亭不耐受或耐药患者中的效果。我们回顾性分析了比利时9个中心455例(102例男性和353例女性)接受卡麦角林治疗的病理性高泌乳素血症患者的病历。这些患者中,41%患有微腺瘤;42%患有大腺瘤;16%为特发性高泌乳素血症;1%为空蝶鞍。治疗前血清PRL水平中位数为124μg/L(范围为16 - 26,250μg/L)。292例患者的亚组此前曾接受溴隐亭治疗,其中140例表现为溴隐亭不耐受,58例表现为溴隐亭耐药。卡麦角林治疗使所有患者中86%的血清PRL水平恢复正常:特发性高泌乳素血症或微泌乳素瘤患者中的244例(92%)以及181例大腺瘤患者中的77%。治疗前70%的患者视野异常恢复正常,67%的病例肿瘤缩小。13%的患者出现副作用,但仅3.9%因副作用停药。治疗开始时卡麦角林的中位剂量为1.0mg/周,但一旦病情得到控制可减至0.5mg/周。与特发性高泌乳素血症或微泌乳素瘤患者相比,大泌乳素瘤患者所需卡麦角林的中位剂量更高:分别为1.0mg/周和0.5mg/周,尽管两组之间有很大重叠。27例接受卡麦角林治疗的女性怀孕,25例分娩出健康婴儿。1例患者人工流产,另1例流产。在溴隐亭不耐受患者中,84%的病例PRL恢复正常,而在溴隐亭耐药患者中,70%的患者PRL可恢复正常。在一项大规模回顾性研究中,我们证实卡麦角林治疗病理性高泌乳素血症疗效高且耐受性好,很少有患者出现无法接受的副作用或临床反应不佳。特发性高泌乳素血症或微泌乳素瘤患者平均所需卡麦角林剂量仅为大泌乳素瘤患者的一半,且PRL恢复正常的机会更高。卡麦角林也使大多数已知对溴隐亭不耐受或耐药的患者PRL恢复正常。一旦PRL分泌得到充分控制,卡麦角林剂量通常可显著降低,这进一步降低了治疗成本。