Endocrinology Service and the Experimental Endocrinology Unit, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, MX, USA.
Pathology Department, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, MX, USA.
Endocrine. 2018 Aug;61(2):343-348. doi: 10.1007/s12020-018-1638-9. Epub 2018 Jun 11.
Dopamine agonist (DA)-resistant prolactinomas are rare but they constitute a real challenge, since there are few therapeutic alternatives left for these patients.
Proof-of-concept study at a tertiary care, referral center.
The studied population consisted of five patients (one female and four males, mean age at diagnosis 23.5 ± 19) with macroprolactinomas with persistent hyperprolactinemia and/or tumor mass despite high doses of cabergoline (CBG) and pituitary surgery, to whom 20 mg monthly of octreotide LAR was added for 6-13 months. Response was evaluated by measuring prolactin (PRL) levels and by magnetic resonance imaging. Immunohistochemistry (IHC) for pituitary hormones, Ki-67, and somatostatin receptor subtypes 2 and 5 was (SSTR2 and 5) was available in two of the subjects.
The addition of octreotide LAR to ongoing CBG treatment had no effect on either PRL levels or tumor size in three patients. In two of the five patients, combination treatment resulted in a significant reduction in PRL concentrations (from 7643 to 200 ng/mL and from 2587 to 470 ng/mL) as well as in adenoma size (93% reduction). IHC evaluation of tumor samples from two patients (a responder and a non-responder) revealed positive immunostaining for PRL and SSTR5 but not for other pituitary hormones or for SSTR2.
The addition of a somatostatin analog to ongoing CBG treatment may be effective in some patients with DA-resistant macroprolactinomas, independently of the adenoma's SSTR expression profile.
多巴胺激动剂（DA）耐药性泌乳素瘤较为罕见，但它们确实构成了一个挑战，因为这些患者的治疗选择有限。
在一家三级医疗保健转诊中心进行的概念验证研究。
研究人群包括五名患者（一名女性和四名男性，诊断时的平均年龄为 23.5±19 岁），他们患有大泌乳素瘤，尽管使用了高剂量卡麦角林（CBG）和垂体手术，但仍存在持续性高泌乳素血症和/或肿瘤体积。在这五名患者中，有三名患者在接受 CBG 治疗的同时加用每月 20mg 的奥曲肽 LAR，但治疗 6-13 个月后，这三名患者的泌乳素（PRL）水平和磁共振成像结果均无变化。在这两名患者中，对肿瘤组织进行了垂体激素、Ki-67 和生长抑素受体亚型 2 和 5（SSTR2 和 5）的免疫组化（IHC）检测。
在三名患者中，奥曲肽 LAR 联合 CBG 治疗对 PRL 水平或肿瘤大小均无影响。在五名患者中的两名患者中，联合治疗使 PRL 浓度（从 7643 降至 200ng/mL 和从 2587 降至 470ng/mL）和腺瘤体积（减少 93%）显著降低。对两名患者（一名有反应者和一名无反应者）的肿瘤样本进行 IHC 评估显示，PRL 和 SSTR5 的免疫染色呈阳性，但其他垂体激素和 SSTR2 则无阳性染色。
在一些 DA 耐药性大泌乳素瘤患者中，在继续使用 CBG 治疗的同时添加生长抑素类似物可能是有效的，而与腺瘤的 SSTR 表达谱无关。
