Abs R, Verhelst J, Maiter D, Van Acker K, Nobels F, Coolens J L, Mahler C, Beckers A
Department of Endocrinology, University Hospital, Antwerp, Belgium.
J Clin Endocrinol Metab. 1998 Feb;83(2):374-8. doi: 10.1210/jcem.83.2.4556.
Cabergoline is a new, long acting, dopamine agonist that is more effective and better tolerated than bromocriptine in patients with hyperprolactinemia. Because dopamine agonists still have a place in the medical management of acromegaly, cabergoline might be a useful treatment. We, therefore, evaluated the effect of long term administration of cabergoline in a large group of unselected acromegalic patients. Sixty-four patients were included in a multicenter, prospective, open labeled study. A subgroup of 16 patients had GH-/PRL-cosecreting pituitary adenomas. Cabergoline was started at a dose of 1.0 mg/week and was gradually increased until normalization of plasma insulin-like growth factor I (IGF-I) levels, occurrence of unacceptable side-effects, or a maximal weekly dose of 3.5 mg (7.0 mg in 1 case) was reached. Treatment with cabergoline suppressed plasma IGF-I below 300 micrograms/L in 39% of cases and between 300-450 micrograms/L in another 28%. With pretreatment plasma IGF-I concentrations less than 750 micrograms/L, a suppression of IGF-I below 300 micrograms/L was obtained in 53% of cases, and a suppression between 300-450 micrograms/L was obtained in another 32%. By contrast, with pretreatment plasma IGF-I concentrations above 750 micrograms/L, only 17% of cases showed a suppression of IGF-I below 300 micrograms/L, and there was IGF-I suppression between 300-450 micrograms/L in another 21%. In GH-/PRL-cosecreting adenomas, 50% of cases suppressed plasma IGF-I levels below 300 micrograms/L, and another 31% did so between 300-450 micrograms/L, in contrast to only 35% and 27%, respectively in GH-secreting adenomas. Similar results were obtained concerning the secretion of GH. Tumor shrinkage was demonstrated in 13 of 21 patients, with a mass reduction by more than half in 5 GH-/PRL-cosecreting adenomas. Except for slight gastrointestinal discomfort and orthostatic hypotension in a few patients at the beginning of therapy, cabergoline treatment was well tolerated. Only 2 patients stopped medication because of nausea. The weekly dose of cabergoline ranged between 1.0-1.75 mg. A further increase in the dose was only effective in 1 GH-/PRL-cosecreting adenoma. The results of this study suggest that cabergoline is an effective, well tolerated therapy that should be considered in the management of acromegaly, especially if the pituitary adenoma cosecretes GH and PRL or if pretreatment plasma IGF-I levels are below 750 micrograms/L.
卡麦角林是一种新型长效多巴胺激动剂,在高泌乳素血症患者中比溴隐亭更有效且耐受性更好。由于多巴胺激动剂在肢端肥大症的药物治疗中仍占有一席之地,卡麦角林可能是一种有效的治疗方法。因此,我们评估了对一大组未经挑选的肢端肥大症患者长期给予卡麦角林的效果。64例患者纳入一项多中心、前瞻性、开放标签研究。16例患者的亚组患有生长激素/泌乳素共分泌型垂体腺瘤。卡麦角林起始剂量为1.0mg/周,并逐渐增加剂量,直至血浆胰岛素样生长因子I(IGF-I)水平恢复正常、出现不可接受的副作用或达到最大每周剂量3.5mg(1例为7.0mg)。卡麦角林治疗使39%的患者血浆IGF-I水平降至300μg/L以下,另有28%的患者血浆IGF-I水平介于300 - 450μg/L之间。预处理时血浆IGF-I浓度低于750μg/L的患者中,53%的患者血浆IGF-I水平降至300μg/L以下,另有32%的患者血浆IGF-I水平介于300 - 450μg/L之间。相比之下,预处理时血浆IGF-I浓度高于750μg/L的患者中,仅17%的患者血浆IGF-I水平降至300μg/L以下,另有21%的患者血浆IGF-I水平介于300 - 450μg/L之间。在生长激素/泌乳素共分泌型腺瘤患者中,50%的患者血浆IGF-I水平降至300μg/L以下,另有31%的患者血浆IGF-I水平介于300 - 450μg/L之间,而在生长激素分泌型腺瘤患者中,这一比例分别仅为35%和27%。关于生长激素的分泌也得到了类似结果。21例患者中有13例出现肿瘤缩小,5例生长激素/泌乳素共分泌型腺瘤的肿瘤体积缩小超过一半。除少数患者在治疗开始时出现轻微胃肠道不适和体位性低血压外,卡麦角林治疗耐受性良好。仅2例患者因恶心停药。卡麦角林的每周剂量介于1.0 - 1.75mg之间。剂量进一步增加仅对1例生长激素/泌乳素共分泌型腺瘤有效。本研究结果表明,卡麦角林是一种有效且耐受性良好的治疗方法,在肢端肥大症的治疗中应予以考虑,尤其是垂体腺瘤同时分泌生长激素和泌乳素或预处理时血浆IGF-I水平低于750μg/L的患者。