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

Department of Internal Medicine, Cliniques de Mont-Godinne, Mont-Godinne Hospital, Université Catholique de Louvain, B-5530 Mont-sur-Meuse, Belgium¹ Department of Endocrinology, University of Antwerp, B-2610 Antwerp, Belgium² Department of Endocrinology, Middelheim Hospital, B-2610 Antwerp, Belgium³ Department of Endocrinology, Cliniques Saint-Luc, Université Catholique de Louvain, B-1200 Brussels, Belgium

(Correspondence should be addressed to E Delgrange; Email: etienne.delgrange{at}uclouvain.be)

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 (CAB) on the basis of a dose–response relationship established in a large series of macroprolactinoma patients and to assess the influence of gender and tumor invasiveness on the response to treatment.

Design: Retrospective study.

Methods: One hundred and twenty-two patients (72 women and 50 men) primarily treated with CAB for at least 1 year were included. Main outcome measures were serum prolactin (PRL) and tumor size.

Results: Normalization of PRL was obtained in 115 out of the 122 patients (94%). The majority of patients (96/115, 83%) were controlled with a CAB dose 1.5 mg/week. Most of the other patients (19/26) had only a partial resistance, responding to a further increase of the CAB 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 CAB treatment. It was more likely to occur in cases of PRL 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 CAB 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 of CAB. We suggest defining such patients as resistant to CAB.