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      Management of macroprolactinomas

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          Abstract

          Prolactin (PRL) secreting tumors are the most common functional neoplasms of the pituitary and are commonly subdivided into microprolactinomas (<10 mm) and macroprolactinomas (≥10 mm) according to their baseline diameter. Patients with prolactinoma present with symptoms evolving from hyperprolactinemia and with those caused by pressure of the expanding mass on surrounding tissues, including the optic chiasm and the cavernous sinuses. We hereby describe the possible complications of macroprolactinomas, including mass effects, hypopituitarism, CSF leak and apoplexy and discuss their relevant management.

          In general, all patients harboring macroprolactinomas should be treated, the objectives being to achieve normal or near normal PRL levels, to reduce or stabilize adenoma size and to recover altered pituitary axes. Medical therapy with dopamine agonists (DA) is the preferred initial treatment for the vast majority of patients harboring prolactinomas. Pituitary surgery is indicated in patients who cannot tolerate or are resistant to therapy with DAs, patients that seek fertility and harbor adenomas that impinge on the optic chiasm, psychiatric patients with contraindication to DA treatment and patients presenting with pituitary apoplexy or a cerebrospinal fluid (CSF) leak. In addition, in this review, several patient populations with unique clinical characteristics will be discussed separately namely postmenopausal women, the elderly, children and patients with pituitary carcinoma.

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          Most cited references 96

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          Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline.

          The aim was to formulate practice guidelines for the diagnosis and treatment of hyperprolactinemia. The Task Force consisted of Endocrine Society-appointed experts, a methodologist, and a medical writer. This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of The Endocrine Society, The European Society of Endocrinology, and The Pituitary Society reviewed and commented on preliminary drafts of these guidelines. Practice guidelines are presented for diagnosis and treatment of patients with elevated prolactin levels. These include evidence-based approaches to assessing the cause of hyperprolactinemia, treating drug-induced hyperprolactinemia, and managing prolactinomas in nonpregnant and pregnant subjects. Indications and side effects of therapeutic agents for treating prolactinomas are also presented.
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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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              Pituitary adenoma predisposition caused by germline mutations in the AIP gene.

              Pituitary adenomas are common in the general population, and understanding their molecular basis is of great interest. Combining chip-based technologies with genealogy data, we identified germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene in individuals with pituitary adenoma predisposition (PAP). AIP acts in cytoplasmic retention of the latent form of the aryl hydrocarbon receptor and also has other functions. In a population-based series from Northern Finland, two AIP mutations account for 16% of all patients diagnosed with pituitary adenomas secreting growth hormone and for 40% of the subset of patients who were diagnosed when they were younger than 35 years of age. Typically, PAP patients do not display a strong family history of pituitary adenoma; thus, AIP is an example of a low-penetrance tumor susceptibility gene.
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                Author and article information

                Affiliations
                [1 ]GRID grid.413156.4, ISNI 000000040575344X, , Institute of Endocrinology, Rabin Medical Center, ; Beilinson Campus, Petah Tiqva, 4941492 Israel
                [2 ]GRID grid.12136.37, ISNI 0000000419370546, , Felsenstein Medical Research Center, Sackler School of Medicine, Tel Aviv University, ; Tel Aviv-Yafo, Israel
                Contributors
                tiroshamit@gmail.com
                +972-54-5749044 , ilanshi@clalit.org.il
                Journal
                Clin Diabetes Endocrinol
                Clin Diabetes Endocrinol
                Clinical Diabetes and Endocrinology
                BioMed Central (London )
                2055-8260
                20 July 2015
                20 July 2015
                2015
                : 1
                5469196 6 10.1186/s40842-015-0006-4
                © Tirosh and Shimon. 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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                Review Article
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                © The Author(s) 2015

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