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      Predictors of dopamine agonist resistance in prolactinoma patients

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          Abstract

          Background

          Surgical resection of prolactinomas resistant to dopamine agonists is frequently incomplete due to fibrotic changes of the tumour under pharmacological therapy. In order to identify a subgroup of patients who may benefit from early surgery, we thought to investigate possible predictive factors of pharmacological resistance of prolactinomas to dopamine agonists.

          Methods

          We retrospectively analyzed a database of a Belgian tertiary reference center for patients with pituitary tumours from 2014 to 2016. The groups of interest were patients with dopamine agonist responsive and resistant prolactinomas. The possible predictive factors, including MRI findings, endocrinological parameters, response of tumour and patient factors for dopamine agonist resistance were investigated.

          Results

          We included 69 patients of whom 52 were women (75,4%) and 17 were men (24,6%). Rate of dopamine agonist resistance was 15.9%. We identified four significant predictors of dopamine agonist resistance: male gender, a large tumour volume, prolonged time to prolactin normalization and presence of a cystic, hemorrhagic and/or necrotic component. In addition, symptoms due to mass effect, high baseline prolactin level and a high contrast capture on MRI are factors that can be taken into consideration.

          Conclusion

          We identified predictive factors for pharmacological resistance and developed a scoring system for patient specific prediction of resistance to dopamine agonists. This scoring system may have impact on the timing and decision of surgery in prolactinoma patients after further prospective evaluation.

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          Most cited references 23

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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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            Prolactinomas resistant to standard doses of cabergoline: a multicenter study of 92 patients.

            Dopamine agonist resistance in prolactinoma is an infrequent phenomenon. Doses of cabergoline (CAB) of up to 2.0 mg/week are usually effective in controlling prolactin (PRL) secretion and reducing tumor size in prolactinomas. The clinical presentation, management, and outcome of patients that are not well controlled by such commonly used doses of CAB-resistant patients are poorly understood.
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              Management of medically refractory prolactinoma.

               Mark Molitch (2014)
              Resistance to dopamine agonists is defined here as failure to normalize prolactin levels and failure to decrease macroprolactinoma size by ≥50 %. Failure to normalize prolactin levels is found in about 25 % of patients treated with bromocriptine and 10-15 % 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 cabergoline. Treatment approaches for patients resistant to dopamine agonists include changing to another dopamine agonist and increasing the dose of the drug as long as there is continued response to the dose increases and no adverse effects with higher doses. Transsphenoidal surgery is also an option. Clomiphene, gonadotropins, and GnRH can be used if fertility is desired. For those not desiring fertility, 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. In many patients modest or even no reduction in tumor size may be acceptable as long as there is not tumor growth. Hormone replacement [estrogen or testosterone] may cause a decrease in efficacy of the dopamine agonist. Reduction of endogenous estrogen, use of selective estrogen receptor modulators, and aromatase inhibitors are potential experimental approaches. Temozolomide may be useful as a last resort for aggressive, invasive tumors refractory to other medical and ablative therapies.
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                Author and article information

                Contributors
                Sven.Glasker@vub.be
                Journal
                BMC Endocr Disord
                BMC Endocr Disord
                BMC Endocrine Disorders
                BioMed Central (London )
                1472-6823
                19 May 2020
                19 May 2020
                2020
                : 20
                Affiliations
                [1 ]GRID grid.411326.3, ISNI 0000 0004 0626 3362, Department of Neurosurgery, , VUB University Hospital of Brussels, ; Laarbeeklaan 101, 1090 Brussels, Belgium
                [2 ]GRID grid.411326.3, ISNI 0000 0004 0626 3362, Department of Radiology, , VUB University Hospital of Brussels, ; Laarbeeklaan 101, 1090, Brussels, Belgium
                [3 ]GRID grid.411326.3, ISNI 0000 0004 0626 3362, Department of Endocrinology, , VUB University Hospital of Brussels, ; Laarbeeklaan 101, 1090, Brussels, Belgium
                [4 ]GRID grid.411326.3, ISNI 0000 0004 0626 3362, Department of Statistics, , VUB University Hospital of Brussels, ; Laarbeeklaan 101, 1090, Brussels, Belgium
                Article
                543
                10.1186/s12902-020-0543-4
                7236128
                32429916
                © The Author(s). 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data.

                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100003130, Fonds Wetenschappelijk Onderzoek;
                Award ID: FWO-V 1831017 N
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2020

                Endocrinology & Diabetes

                pituitary adenoma, prolactinoma, resistance, dopamine agonist

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