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      Pituitary surgery for small prolactinomas as an alternative to treatment with dopamine agonists

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          Abstract

          Despite the fact that consensus guidelines recommend long-term dopamine agonist (DA) therapy as a first-line approach to the treatment of small prolactinoma, some patients continue to prefer a primary surgical approach. Concerns over potential adverse effects of long-term medical therapy and/or the desire to become pregnant and avoid long-term medication are often mentioned as reasons to pursue surgical removal. In this retrospective study, 34 consecutive patients (30 female, 4 male) preferably underwent primary pituitary surgery without prior DA treatment for small prolactinomas (microprolactinoma 1–10 mm, macroprolactinoma 11–20 mm) at the Department of Neurosurgery, University of Bern, Switzerland. At the time of diagnosis, 31 of 34 patients (91%) presented with symptoms. Patients with microprolactinomas had significantly lower preoperative prolactin (PRL) levels compared to patients with macroprolactinomas (median 143 μg/l vs. 340 μg/l). Ninety percent of symptomatic patients experienced significant improvement of their signs and symptoms upon surgery. The postoperative PRL levels (median 3.45 μg/l) returned to normal in 94% of patients with small prolactinomas. There was no mortality and no major morbidities. One patient suffered from hypogonadotropic hypogonadism after surgery despite postoperative normal PRL levels. Long-term remission was achieved in 22 of 24 patients (91%) with microprolactinomas, and in 8 of 10 patients (80%) with macroprolactinomas after a median follow-up period of 33.5 months. Patients with small prolactinomas can safely consider pituitary surgery in a specialized centre with good chance of long-term remission as an alternative to long-term DA therapy.

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          Most cited references55

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          Advances in the treatment of prolactinomas.

          Prolactinomas account for approximately 40% of all pituitary adenomas and are an important cause of hypogonadism and infertility. The ultimate goal of therapy for prolactinomas is restoration or achievement of eugonadism through the normalization of hyperprolactinemia and control of tumor mass. Medical therapy with dopamine agonists is highly effective in the majority of cases and represents the mainstay of therapy. Recent data indicating successful withdrawal of these agents in a subset of patients challenge the previously held concept that medical therapy is a lifelong requirement. Complicated situations, such as those encountered in resistance to dopamine agonists, pregnancy, and giant or malignant prolactinomas, may require multimodal therapy involving surgery, radiotherapy, or both. Progress in elucidating the mechanisms underlying the pathogenesis of prolactinomas may enable future development of novel molecular therapies for treatment-resistant cases. This review provides a critical analysis of the efficacy and safety of the various modes of therapy available for the treatment of patients with prolactinomas with an emphasis on challenging situations, a discussion of the data regarding withdrawal of medical therapy, and a foreshadowing of novel approaches to therapy that may become available in the future.
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            Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas.

            In June 2005, an ad hoc Expert Committee formed by the Pituitary Society convened during the 9th International Pituitary Congress in San Diego, California. Members of this committee consisted of invited international experts in the field, and included endocrinologists and neurosurgeons with recognized expertise in the management of prolactinomas. Discussions were held that included all interested participants to the Congress and resulted in formulation of these guidelines, which represent the current recommendations on the diagnosis and management of prolactinomas based upon comprehensive analysis and synthesis of all available data.
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              A comparison of cabergoline and bromocriptine in the treatment of hyperprolactinemic amenorrhea. Cabergoline Comparative Study Group.

              Cabergoline is a long-acting dopamine-agonist drug that suppresses prolactin secretion and restores gonadal function in women with hyperprolactinemic amenorrhea. We designed a study to compare its safety and efficacy with those of bromocriptine, which has been the standard therapy. A total of 459 women with hyperprolactinemic amenorrhea were treated with either cabergoline (0.5 to 1.0 mg twice weekly) or bromocriptine (2.5 to 5.0 mg twice daily), administered in a double-blind fashion for 8 weeks and subsequently in an open fashion for 16 weeks, during which adjustments in the dose were made according to the response. Of the 459 women, 279 had microprolactinomas, 3 had macroprolactinomas, 1 had a craniopharyngioma, 167 had idiopathic hyperprolactinemia, and the remainder had an empty sella. Clinical and biochemical status was assessed at 2-week intervals for 8 weeks and monthly thereafter for a total of 6 months, with an additional assessment at 14 weeks. Stable normoprolactinemia was achieved in 186 of the 223 women treated with cabergoline (83 percent) and 138 of the 236 women treated with bromocriptine (59 percent, P < 0.001). Seventy-two percent of the women treated with cabergoline and 52 percent of those treated with bromocriptine had ovulatory cycles or became pregnant during treatment (P < 0.001). Amenorrhea persisted in 7 percent of the cabergoline-treated women and 16 percent of the bromocriptine-treated women. Adverse effects were recorded in 68 percent of the women taking cabergoline and 78 percent of those taking bromocriptine (P = 0.03); 3 percent discontinued taking cabergoline, and 12 percent stopped taking bromocriptine (P < 0.001) because of drug intolerance. Gastrointestinal symptoms were significantly less frequent, less severe, and shorter-lived in the women treated with cabergoline. Cabergoline is more effective and better tolerated than bromocriptine in women with hyperprolactinemic amenorrhea.
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                Author and article information

                Contributors
                +1-415-2114810 , +1-415-7506929 , muriel.babey@ucsf.edu
                +41-31-6323039 , +41-31-6328414 , rahel.sahli@insel.ch
                Journal
                Pituitary
                Pituitary
                Springer US (Boston )
                1386-341X
                1573-7403
                18 December 2010
                18 December 2010
                September 2011
                : 14
                : 3
                : 222-230
                Affiliations
                [1 ]Department of Neurosurgery, University of Berne, Inselspital, 3010 Berne, Switzerland
                [2 ]Division of Endocrinology, Diabetes and Clinical Nutrition, University of Berne, Inselspital, 3010 Berne, Switzerland
                [3 ]Endocrine Research Unit, Division of Endocrinology, University of California, San Francisco, 4150 Clement Street, San Francisco, CA 94121 USA
                [4 ]Institute of Pathology, University of Berne, Inselspital, 3010 Berne, Switzerland
                Article
                283
                10.1007/s11102-010-0283-y
                3146980
                21170594
                0a2ce38d-ed90-4f9f-8362-240f91c104b1
                © The Author(s) 2010
                History
                Categories
                Article
                Custom metadata
                © Springer Science+Business Media, LLC 2011

                Medicine
                hyperprolactinemia,prolactin,dopamine agonists,microprolactinomas,pituitary surgery,prolactinomas,macroprolactinomas

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