Characterization of resistance to the prolactin-lowering effects of cabergoline in macroprolactinomas : a study in 122 patients

Context: Macroprolactinomas poorly responsive to dopamine-agonists are often more aggressive and are usually termed resistant but this clinical concept has always been defined empirically. Objective: To define resistance to cabergoline on the basis of a dose-response relationship established in a large series of macroprolactinoma patients and to assess the influence of gender and of tumor invasiveness on the response to treatment. Design: Retrospective study. Methods: 122 patients (72 women and 50 men) primarily treated with cabergoline for at least one year were included. Main outcome measures were serum prolactin and tumor size. Results: Normalization of prolactin was obtained in 115 of the 122 patients (94%). The majority of patients (96/115, 83%) was controlled with a cabergoline dose < 1.5 mg/week. Most of the other patients (19/26) had only a partial resistance, responding to a further increase of the cabergoline dose. Beyond the dose of 3.5 mg/week, there was no clear advantage in further increasing the dose instead of continuing the treatment at the same dose. Most tumors (98/119 assessable cases, 82%) showed a significant shrinkage during cabergoline treatment. It was more likely to occur in cases of prolactin normalization. Both cavernous sinus invasion and male gender were significantly and independently associated with partial or complete resistance to treatment. Conclusions: Most macroprolactinomas primarily treated with cabergoline are adequately controlled with doses < 1.5 mg/week. About 20% of patients, mainly men and/or those with invasive tumors, will require a higher dose. We suggest defining such patients as resistant to cabergoline