7
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Prolactinomas resistentes a agonistas dopaminérgicos: diagnóstico e manejo Translated title: Dopamine-agonists-resistant prolactinomas: diagnosis and management

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Prolactinomas são os tumores hipofisários funcionantes mais freqüentes, sendo as drogas agonistas dopaminérgicas (AD) a principal opção para seu tratamento. Resistência à bromocriptina (BRC), primeiro AD a ser utilizado, definida como ausência de normalização da prolactina (PRL) ou de redução tumoral durante o tratamento, é relatada em 5 a 18% dos pacientes tratados. Novos AD, como a cabergolina (CBG), são alternativa eficaz já que podem normalizar a PRL e reduzir tumores em até 86% e 92% dos casos, respectivamente. Mesmo assim, uma porcentagem dos pacientes pode ser chamada de resistente aos AD. Os mecanismos para a resistência ainda não são completamente elucidados e, embora pouco freqüentes, os prolactinomas resistentes aos AD representam um desafio para o tratamento. As alternativas como cirurgia e radioterapia podem não alcançar a normalização da PRL e, portanto, não resolver os sintomas ligados à hiperprolactinemia. Tratamento do hipogonadismo com reposição de esteróides sexuais, assim como estimulação ovulatória quando o desejo for a gravidez, podem ser alternativas para casos com crescimento tumoral controlado. Novas drogas como anti-estrógenos, novos AD, análogos específicos de subtipos do receptor da somatostatina, drogas quiméricas com ação no receptor da somatostatina e da dopamina e antagonistas da PRL estão sendo estudados e podem representar alternativas futuras ao tratamento deste grupo de pacientes.

          Translated abstract

          Prolactinomas are the more prevalent functioning pituitary tumors, and dopamine agonist drugs (DA) are the main therapeutic option for patients harboring such tumors. Bromocriptine (BRC) resistance, defined as failure to normalize prolactin (PRL) and/or to shrink the tumor is reported in 5 to 18% of the patients treated with this drug, the first DA widely used. Cabergoline (CBG) can bring PRL to normalization and reduce tumor size in up to 86% and 92% of the patients, respectively. Even with this newer DA, a subset of patients does not respond to therapy and are truly resistant. The mechanisms for resistance are not yet fully clarified, so the treatment for the resistant prolactinoma is still a challenge. Transsphenoidal surgery associated or not to radiotherapy is an important tool, but PRL may not normalize, mainly in macroprolactinomas. Treatment with sex steroids or ovulation induction can solve the hypogonadism or infertility, when the tumor growth is under control. New drugs as anti-estrogens, new DA, specific analogs for somatostatin receptor subtypes, chimeric molecules associating dopamine and somatostatin effect, and PRL antagonists are under investigation and can be future alternatives for DA resistance.

          Related collections

          Most cited references 52

          • Record: found
          • Abstract: found
          • Article: not found

          Medical management of prolactin-secreting pituitary adenomas.

           Mark Molitch (2002)
          Prolactinomas are a common cause of reproductive/sexual dysfunction. Once other causes of hyperprolactinemia have been excluded with a careful history and physical examination, routine chemistries, a pregnancy test and a TSH, imaging with MRI or CT will delineate the size and extent of the tumor. Medical therapy is the initial treatment of choice. When infertility is the primary indication for treatment, bromocriptine use has an extensive safety experience and is preferred. However, for other indications, cabergoline appears to be more efficacious and better tolerated. Transsphenoidal surgery remains an option, especially for patients with microadenomas, when medical therapy is ineffective.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Dopamine resistance of prolactinomas.

             Mark Molitch (2002)
            Resistance to dopamine agonists can be defined with respect to failure to normalize PRL levels and failure to decrease tumor size by > or = 50%. Using these definitions, failure to normalize PRL levels is seen in 24% of those treated with bromocriptine, 13% of those treated with pergolide and 11% of those treated with cabergoline. Failure to achieve at least a 50% reduction in tumor size occurs in about one-third of those treated with bromocriptine and 10-15% of those treated with pergolide or cabergoline. Studies of in vitro cell preparations show that the D2 receptors of resistant tumors are decreased in number but have normal affinity. Treatment approaches for resistant patients include switching to another dopamine agonist and raising the dose of the drug as long as there is continued response to the dose increases and no adverse effects. Transsphenoidal surgery can also be done. If fertility is desired, clomiphene, gonadotropins, and GnRH are also options. If fertility is not desired, estrogen replacement may be used unless there is a macroadenoma, in which case control of tumor growth is also an issue and dopamine agonists are generally necessary. However, in many cases modest or even no reduction may be acceptable long-term as long as there is not tumor growth. Hormone replacement (estrogen or testosterone) may cause a decrease in efficacy of the dopamine agonist so that it must be carried out cautiously. Reduction of endogenous estrogen, use of selective estrogen receptor modulators, and aromatase inhibitors are potential experimental approaches.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Perivascular fibrosis in prolactinomas: is it increased by bromocriptine?

              Prolonged treatment of patients with pituitary prolactinomas with bromocriptine may increase the consistency of the tumor thereby making selective extirpation more difficult. We made quantitative determinations of the amount of perivascular fibrous tissue in prolactinomas on random electron micrographs, comparing a group of 21 patients treated with bromocriptine for periods longer than 3 months and a control group of 21 patients who did not receive bromocriptine. Statistical analysis of the data showed a significant increase of perivascular fibrous tissue in the treated group (P less than 0.002). We suspect that this fibrosis is a consequence of the rapid shrinkage of prolactinoma cells caused by bromocriptine. Presumably, this cell shrinkage causes enlargement of the extracellular and perivascular spaces which are filled by the deposition of collagen, producing a more dense consistency of the adenoma.
                Bookmark

                Author and article information

                Contributors
                Role: ND
                Role: ND
                Journal
                abem
                Arquivos Brasileiros de Endocrinologia & Metabologia
                Arq Bras Endocrinol Metab
                Sociedade Brasileira de Endocrinologia e Metabologia (São Paulo )
                1677-9487
                October 2005
                : 49
                : 5
                : 641-650
                Affiliations
                [1 ] Instituto de Psiquiatria
                [2 ] Universidade de São Paulo Brazil
                Article
                S0004-27302005000500005
                10.1590/S0004-27302005000500005
                Product
                Product Information: website
                Categories
                ENDOCRINOLOGY & METABOLISM

                Comments

                Comment on this article