PROLACTINOMAS RESISTANT TO BROMOCRIPTINE - LONG-TERM EFFICACY OF QUINAGOLIDE AND OUTCOME OF PREGNANCY

Resistance to bromocriptine, defined as the absence of normalization o f prolactin (PRL) levels despite a 15-30 mg daily dose of bromocriptin e during at least 6 months, has been observed in 5-17% of the prolacti nomas according to the literature. The recent availability of a new po tent dopamine agonist, quinagolide, prompted us to analyze its long-te rm therapeutic effects in 28 patients with prolactinomas resistant to bromocriptine. Before bromocriptine, their PRL levels were 520 +/- 185 mu g/l (mean +/- SEM) and decreased to 291 +/- 154 mu g/l after a 6-2 1 month period of bromocriptine treatment. All the women (N = 20) rema ined amenorrheic and hypogonadism was not improved in men (N = 8). Sub sequently, after 1 year of 150-300 mu g/day quinagolide, 12/28 patient s of the present series recovered normal gonadal function and their in itial mean baseline PRL value (404 +/- 180 mu g/l) was 16 +/- 2 mu g/l after 1 year of treatment. A significant tumor shrinkage was observed in 5/8 macroadenomas (62%). During the 3-year follow-up period under quinagolide, a similar good control was achieved in these patients, wi th the exception of one man presenting with a secondary rise of PRL un der quinagolide. In contrast, 15 other patients (one patient interrupt ed quinagolide at 6 months because of poor tolerance) were not normali zed under 150-450 mu g/day quinagolide. Their initial PRL levels (606 +/- 298 mu g/l) were reduced to 343 +/- 187 mu g/l (versus 463 +/- 265 mu g/l under bromocriptine after the same duration of treatment). Des pite such a partial inhibitory effect of quinagolide, 7/12 women resum ed menstrual cycles and three pregnancies occurred. In no case was any tumor shrinkage noticed during the 3-4-year follow-up. Three patients even presented, after 2 pears of quinagolide treatment, with a second ary rise of PRL values associated with a further tumor growth in two p atients. During the 3-year follow-up period, nine pregnancies occurred in seven women. In fine women, after quinagolide withdrawal, the plas ma PRL baseline values ranged from 52 to 158 mu g/l and from 65 to 192 mu g/l, respectively, at the first trimester and at the end of uneven tful pregnancies. In contrast, in two women a rapid increase of PRL (2 40-400 mu g/l) correlated with tumor growth during the first trimester . Such a tumor progression was blocked by quinagolide treatment but no t by bromocriptine. These data, although observed in a limited series, justify the careful follow-up of pregnancies in this subclass of pati ents at risk. Finally, in the whole population, long-term control of h yperprolactinemia by quinagolide was obtained in 11/28 patients (39%) previously resistant to bromocriptine, and 15/20 women (75%) resumed n ormal gonadal function with a quinagolide daily dose of 300 mu g in mo st of them.