Corsello S M, Ubertini G, Altomare M, Lovicu R M, Migneco M G, Rota C A, Colosimo C
Institute of Endocrinology, Catholic University School of Medicine, Rome, Italy.
Clin Endocrinol (Oxf). 2003 May;58(5):662-70. doi: 10.1046/j.1365-2265.2003.01770.x.
The term 'giant prolactinoma' can be used for tumours larger than 4 cm in diameter and/or with massive extrasellar extension. Cabergoline (CAB), a long-lasting dopamine agonist (DA), safe and well tolerated, is effective in normalizing PRL levels and inducing tumour shrinkage in micro- and macroprolactinomas. The purpose of this prospective study was to evaluate the efficacy and safety of CAB also for giant prolactinomas.
Ten men with giant prolactinomas with a median age of 44.8 years were treated with CAB. Before CAB, four patients had previously undergone transsphenoidal surgery without modifying the parasellar extension of the tumour or their visual defects. Pretreatment serum prolactin (PRL) levels ranged between 1230 and 22 916 micro g/l (mean +/- SEM: 5794 +/- 1996) and tumour volume was between 21.8 and 105.5 cm3 (mean +/- SEM: 50.7 +/- 8.8). CAB was administered at an initial low dose of 0.5 mg three times a week and, in five patients who did not achieve serum PRL normalization, the dose was progressively increased up to 10.5 mg/week. The duration of treatment was 13-68 months (mean 38.9). PRL levels and pituitary target organ hormones were assayed before, after 30 days and then every 3 months after the beginning of CAB treatment. Magnetic resonance imaging (MRI) was carried out before, after 1-3 months, after 6 months and then every 10-12 months to evaluate tumour shrinkage.
In every patient, a significant PRL decrease (P = 0.0086) of at least 96% of the pretreatment values occurred (from 5794 +/- 1996 to 77 +/- 38, mean +/- SEM); a persistent normalization of PRL levels was achieved in five out of 10 patients (50%) beginning from the first 3-6 months of CAB treatment (only one patient needed 12 months of therapy). A significant tumour shrinkage (P = 0.0003) was achieved after 12 months of therapy in nine out of 10 patients (90%), with a volume reduction greater than 95% in three, of 50% in four and 25% in two patients. Tumour volume decreased from 50.7 +/- 8.8 to 28.6 +/- 9.4 and then to 22.3 +/- 8.8 cm3 (mean +/- SEM) after 6 and 12 months of CAB treatment, respectively. An improvement of visual field defects (VFD) was obtained in six of the seven patients presenting visual impairment before CAB treatment. Among the eight patients presenting libido and potency (L-P) failure, five normalized their PRL levels. In two of these a complete restoration of libido and potency was observed. Three patients with secondary hypoadrenalism and a patient with secondary hypothyroidism were treated with substitutive therapy during all the study time. The drug was well tolerated by all patients and no one discontinued the therapy.
These data suggest that, in giant, aggressive prolactinomas, CAB represents a first-line therapy effective in reducing PRL levels and determining tumour shrinkage.
术语“巨大泌乳素瘤”可用于直径大于4厘米和/或伴有大量鞍外扩展的肿瘤。卡麦角林（CAB）是一种长效多巴胺激动剂（DA），安全且耐受性良好，可有效使微泌乳素瘤和大泌乳素瘤患者的泌乳素（PRL）水平恢复正常并促使肿瘤缩小。这项前瞻性研究的目的是评估CAB治疗巨大泌乳素瘤的疗效和安全性。
10例巨大泌乳素瘤男性患者，中位年龄44.8岁，接受CAB治疗。在使用CAB之前，4例患者曾接受经蝶窦手术，但肿瘤的鞍旁扩展情况或视力缺陷未得到改善。治疗前血清PRL水平在1230至22916微克/升之间（均值±标准误：5794±1996），肿瘤体积在21.8至105.5立方厘米之间（均值±标准误：50.7±8.8）。CAB初始剂量为每周三次，每次0.5毫克，对于5例PRL水平未恢复正常的患者，剂量逐渐增加至每周10.5毫克。治疗持续时间为13至68个月（平均38.9个月）。在CAB治疗开始前、30天后以及之后每3个月检测PRL水平和垂体靶器官激素。在治疗前、1 - 3个月后、6个月后以及之后每10 - 12个月进行磁共振成像（MRI）检查，以评估肿瘤缩小情况。
每位患者的PRL均显著降低（P = 0.0086），至少降至治疗前值的96%（从5794±1996降至77±38，均值±标准误）；10例患者中有5例（50%）从CAB治疗的前3 - 6个月开始PRL水平持续恢复正常（仅1例患者需要12个月的治疗）。治疗12个月后，10例患者中有9例（90%）肿瘤显著缩小（P = 0.0003），3例患者肿瘤体积缩小超过95%，4例患者缩小50%，2例患者缩小25%。CAB治疗6个月和12个月后，肿瘤体积分别从50.7±8.8降至28.6±9.4，然后降至22.3±8.8立方厘米（均值±标准误）。在CAB治疗前有视力损害的7例患者中，6例患者的视野缺损（VFD）得到改善。在出现性欲和性功能（L - P）障碍的8例患者中，5例患者的PRL水平恢复正常。其中2例患者的性欲和性功能完全恢复。在整个研究期间，3例继发性肾上腺皮质功能减退患者和1例继发性甲状腺功能减退患者接受替代治疗。所有患者对该药物耐受性良好，无人停止治疗。
这些数据表明，对于巨大侵袭性泌乳素瘤，CAB是一种有效的一线治疗方法，可有效降低PRL水平并促使肿瘤缩小。
