Ferone D, Lastoria S, Colao A, Varrella P, Cerbone G, Acampa W, Merola B, Salvatore M, Lombardi G
Department of Molecular and Clinical Endocrinology and Oncology, Federico II University, Naples, Italy.
J Clin Endocrinol Metab. 1998 Jan;83(1):248-52. doi: 10.1210/jcem.83.1.4493.
The efficacy of dopaminergic agents in the medical treatment of pituitary adenomas is well known. Quinagolide is a nonergot derivative dopamine agonist, which binds dopamine D2 receptors with high affinity. The treatment with this drug is reported to suppress hormone levels and to cause tumor shrinkage in prolactinomas and in a few GH-secreting pituitary adenomas. In clinically nonfunctioning pituitary adenomas (NFPA), the efficacy of quinagolide treatment is controversial. The scintigraphy of the pituitary region using 123I-methoxybenzamide (123I-IBZM) allows us to visualize in vivo the expression of dopamine D2 receptors on pituitary tumors. In this study, the pituitary scintigraphy with 123I-IBZM was performed in 14 patients with macroadenoma before starting a long-term treatment with quinagolide: 6 NFPA with high circulating alpha-subunit levels, 4 PRL-secreting, and 4 GH-secreting adenomas. A 3-point score was used to grade the ligand accumulation within the pituitary adenomas: 0 = negative, 1 = moderate uptake (equal to that recorded in the cerebral cortex), and 2 = intense uptake (equal to that recorded in the basal nuclei). The treatment with quinagolide was carried out at the dose of 0.3-0.6 mg/day for 6-12 months. Clinical, biochemical and hormonal assessment was repeated monthly during the first 3 months, then quarterly. Sellar magnetic resonance imaging was performed before and after 6 and 12 months of quinagolide treatment, to evaluate tumor shrinkage (> 25% of baseline size). In all 14 patients, a significant positive correlation was found between the degree of 123I-IBZM uptake and the clinical response to quinagolide treatment (r = 0.90; P < 0.001). In particular, the normalization of serum alpha-subunit and PRL levels, respectively, was achieved in 3 patients with NFPA and in 2 patients with prolactinoma, who showed intense 123I-IBZM uptake in the pituitary region. In 4 of these 5 patients with positive scan, a significant tumor shrinkage occurred between 6 and 12 months after the beginning of quinagolide treatment. In all patients with GH-secreting adenoma, no significant uptake of 123I-IBZM was found and no significant decrease of circulating GH and/or insulin-like growth factor-I levels, and tumor shrinkage was obtained during long-term treatment with quinagolide. In conclusion, the pituitary scintigraphy with 123I-IBZM can be considered a useful tool to indicate adenomas with significant expression of functioning D2 receptors. This innovative technique may predict the response to long-term treatment with quinagolide in patients with NFPA, where the lack of pituitary hormone hypersecretion makes difficult the monitoring of medical treatment efficacy.
多巴胺能药物在垂体腺瘤药物治疗中的疗效是众所周知的。喹高利特是一种非麦角衍生物多巴胺激动剂,它以高亲和力结合多巴胺D2受体。据报道,用这种药物治疗可抑制激素水平,并使催乳素瘤和少数生长激素分泌型垂体腺瘤的肿瘤缩小。在临床无功能垂体腺瘤(NFPA)中,喹高利特治疗的疗效存在争议。使用123I-甲氧基苄胺(123I-IBZM)对垂体区域进行闪烁扫描,可使我们在体内观察垂体肿瘤上多巴胺D2受体的表达。在本研究中,对14例大腺瘤患者在开始长期使用喹高利特治疗前进行了123I-IBZM垂体闪烁扫描:6例循环α亚基水平高的NFPA、4例分泌催乳素的腺瘤和4例分泌生长激素的腺瘤。采用三分制对垂体腺瘤内的配体聚集进行分级:0 = 阴性,1 = 中等摄取(等于大脑皮质记录的摄取),2 = 强烈摄取(等于基底核记录的摄取)。喹高利特的治疗剂量为0.3 - 0.6毫克/天,持续6 - 12个月。在最初3个月每月重复进行临床、生化和激素评估,然后每季度进行一次。在喹高利特治疗6个月和12个月前后进行蝶鞍磁共振成像,以评估肿瘤缩小情况(>基线大小的25%)。在所有14例患者中,发现123I-IBZM摄取程度与喹高利特治疗的临床反应之间存在显著正相关(r = 0.90;P < 0.001)。特别是,3例NFPA患者和2例催乳素瘤患者的血清α亚基和催乳素水平分别恢复正常,他们在垂体区域显示出强烈的123I-IBZM摄取。在这5例扫描阳性的患者中,有4例在喹高利特治疗开始后6至12个月出现显著的肿瘤缩小。在所有分泌生长激素的腺瘤患者中,未发现123I-IBZM有显著摄取,循环生长激素和/或胰岛素样生长因子-I水平也没有显著下降,并且在喹高利特长期治疗期间未观察到肿瘤缩小。总之,123I-IBZM垂体闪烁扫描可被认为是一种有用的工具,用于指示具有功能性D2受体显著表达的腺瘤。这种创新技术可能预测NFPA患者对喹高利特长期治疗的反应,在NFPA患者中,缺乏垂体激素分泌过多使得监测药物治疗效果变得困难。