Hospital Universitario Ramón y Cajal, Madrid, Spain.
Endocrinology Department, Hospital Universitario Puerta de Hierro, Madrid, Spain.
Endocrinol Diabetes Nutr (Engl Ed). 2020 Mar;67(3):194-204. doi: 10.1016/j.endinu.2019.04.007. Epub 2019 Jun 11.
Dopamine agonists (DA) are the first-line therapy in prolactinomas, but they fail to decrease prolactin (PRL) levels and/or tumor size in some of these tumors, which are labeled as resistant prolactinomas (RP). To date, risk factors for DA resistance are not fully understood and management of DA-RP is not well established.
We retrospectively recorded clinical, biochemical and radiological features, as well as management and outcome, of all cabergoline (CAB)-RP attended at the Endocrinology department of a tertiary hospital between 1995 and 2016. CAB resistance was defined as the failure to normalize PRL (biochemical resistance, BR) or reduce tumor size by at least 50% (morphological resistance, MR) with a CAB dose up to 2mg/week (or 3mg/week in cases where lower doses were not tested) for at least 3 months.
Ten CAB-RP were found. The mean age of the cohort was 30.6 years and 50% of subjects were male. The average tumor size was 1.78cm (80% macroadenomas). The mean maximal dose of CAB was 3.8mg/week. Five patients showed isolated MR, four combined MR+BR and only one isolated BR. MR patients were more often males and older than MR+BR patients. Transsphenoidal surgery achieved normalization of PRL and/or disappearance of tumor in three of seven patients. At the end of follow up all patients had controlled PRL levels (with or without CAB) and most of them bore a visible although stable tumor.
Isolated MR and combined MR+BR are the most frequent patterns of DA resistance whereas isolated BR seems to be uncommon. Our data support a high tumor size but not male gender as a risk factor for DA resistance.
多巴胺激动剂（DA）是催乳素瘤的一线治疗药物，但在一些被标记为耐药性催乳素瘤（RP）的肿瘤中，它们未能降低催乳素（PRL）水平和/或肿瘤大小。迄今为止，DA 耐药的危险因素尚未完全阐明，DA-RP 的治疗也尚未得到很好的建立。
我们回顾性地记录了 1995 年至 2016 年间在一家三级医院内分泌科就诊的所有卡麦角林（CAB）-RP 的临床、生化和影像学特征、治疗方法和结局。CAB 耐药定义为 CAB 剂量高达 2mg/周（或在未测试较低剂量的情况下为 3mg/周）至少 3 个月后，未能使 PRL 正常化（生化耐药，BR）或使肿瘤大小至少缩小 50%（形态学耐药，MR）。
发现 10 例 CAB-RP。该队列的平均年龄为 30.6 岁，50%的患者为男性。平均肿瘤大小为 1.78cm（80%为大腺瘤）。CAB 的最大平均剂量为 3.8mg/周。5 例患者仅表现为 MR，4 例患者同时表现为 MR+BR，仅 1 例患者仅表现为 BR。MR 患者比 MR+BR 患者更常为男性且年龄更大。经蝶窦手术使 7 例患者中的 3 例 PRL 正常化和/或肿瘤消失。在随访结束时，所有患者的 PRL 水平均得到控制（无论是否使用 CAB），且大多数患者的肿瘤虽然稳定但仍可见。
孤立性 MR 和合并的 MR+BR 是最常见的 DA 耐药模式，而孤立性 BR 似乎不太常见。我们的数据支持大肿瘤体积而不是男性性别是 DA 耐药的危险因素。
