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Published in: BMC Endocrine Disorders 1/2020

01-12-2020 | Pituitary Adenoma | Research article

Predictors of dopamine agonist resistance in prolactinoma patients

Authors: Elle Vermeulen, Jean D’Haens, Tadeusz Stadnik, David Unuane, Kurt Barbe, Vera Van Velthoven, Sven Gläsker

Published in: BMC Endocrine Disorders | Issue 1/2020

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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.
Literature
1.
go back to reference Cao Y, Wang F, Liu Z, Jiao B. Effects of preoperative bromocriptine treatment on prolactin-secreting pituitary adenoma surgery. Exp Ther Med. 2016;11(5):1977–82.PubMedPubMedCentral Cao Y, Wang F, Liu Z, Jiao B. Effects of preoperative bromocriptine treatment on prolactin-secreting pituitary adenoma surgery. Exp Ther Med. 2016;11(5):1977–82.PubMedPubMedCentral
2.
go back to reference Smith TR, Hulou MM, Huang KT, Gokoglu A, Cote DJ, Woodmansee WW, et al. Current indications for the surgical treatment of prolactinomas. J Clin Neurosci. 2015;22(11):1785–91.PubMed Smith TR, Hulou MM, Huang KT, Gokoglu A, Cote DJ, Woodmansee WW, et al. Current indications for the surgical treatment of prolactinomas. J Clin Neurosci. 2015;22(11):1785–91.PubMed
3.
go back to reference Colao A. Pituitary tumours: the prolactinoma. Best Pract Res Clin Endocrinol Metab. 2009;23(5):575–96.PubMed Colao A. Pituitary tumours: the prolactinoma. Best Pract Res Clin Endocrinol Metab. 2009;23(5):575–96.PubMed
4.
go back to reference Vasilev V, Daly AF, Vroonen L, Zacharieva S, Beckers A. Resistant prolactinomas. J Endocrinol Investig. 2011;34(4):312–6. Vasilev V, Daly AF, Vroonen L, Zacharieva S, Beckers A. Resistant prolactinomas. J Endocrinol Investig. 2011;34(4):312–6.
5.
go back to reference Casanueva FF, Molitch ME, Schlechte JA, Abs R, Bonert V, Bronstein MD, et al. Guidelines of the pituitary society for the diagnosis and management of prolactinomas. Clin Endocrinol. 2006;65(2):265–73. Casanueva FF, Molitch ME, Schlechte JA, Abs R, Bonert V, Bronstein MD, et al. Guidelines of the pituitary society for the diagnosis and management of prolactinomas. Clin Endocrinol. 2006;65(2):265–73.
6.
go back to reference Molitch ME. Dopamine resistance of prolactinomas. Pituitary. 2003;6(1):19–27.PubMed Molitch ME. Dopamine resistance of prolactinomas. Pituitary. 2003;6(1):19–27.PubMed
7.
go back to reference Colao A, di Sarno A, Pivonello R, di Somma C, Lombardi G. Dopamine receptor agonists for treating prolactinomas. Expert Opin Investig Drugs. 2002;11(6):787–800.PubMed Colao A, di Sarno A, Pivonello R, di Somma C, Lombardi G. Dopamine receptor agonists for treating prolactinomas. Expert Opin Investig Drugs. 2002;11(6):787–800.PubMed
8.
go back to reference Hamilton DK, Vance ML, Boulos PT, Laws ER. Surgical outcomes in hyporesponsive prolactinomas: analysis of patients with resistance or intolerance to dopamine agonists. Pituitary. 2005;8(1):53–60.PubMed Hamilton DK, Vance ML, Boulos PT, Laws ER. Surgical outcomes in hyporesponsive prolactinomas: analysis of patients with resistance or intolerance to dopamine agonists. Pituitary. 2005;8(1):53–60.PubMed
9.
go back to reference Melmed S, Casanueva FF, Hoffman AR, Kleinberg DL, Montori VM, Schlechte JA, et al. Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(2):273–88. Melmed S, Casanueva FF, Hoffman AR, Kleinberg DL, Montori VM, Schlechte JA, et al. Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(2):273–88.
10.
go back to reference Delgrange E, Daems T, Verhelst J, Abs R, Maiter D. Characterization of resistance to the prolactin-lowering effects of cabergoline in macroprolactinomas: a study in 122 patients. Eur J Endocrinol. 2009;160(5):747–52.PubMed Delgrange E, Daems T, Verhelst J, Abs R, Maiter D. Characterization of resistance to the prolactin-lowering effects of cabergoline in macroprolactinomas: a study in 122 patients. Eur J Endocrinol. 2009;160(5):747–52.PubMed
11.
go back to reference Lee Y, Ku CR, Kim EH, Hong JW, Lee EJ, Kim SH. Early prediction of long-term response to cabergoline in patients with macroprolactinomas. Endocrinol Metab (Seoul). 2014;29(3):280–92. Lee Y, Ku CR, Kim EH, Hong JW, Lee EJ, Kim SH. Early prediction of long-term response to cabergoline in patients with macroprolactinomas. Endocrinol Metab (Seoul). 2014;29(3):280–92.
12.
go back to reference Bevan JS, Adams CB, Burke CW, Morton KE, Molyneux AJ, Moore RA, et al. Factors in the outcome of transsphenoidal surgery for prolactinoma and non-functioning pituitary tumour, including pre-operative bromocriptine therapy. Clin Endocrinol. 1987;26(5):541–56. Bevan JS, Adams CB, Burke CW, Morton KE, Molyneux AJ, Moore RA, et al. Factors in the outcome of transsphenoidal surgery for prolactinoma and non-functioning pituitary tumour, including pre-operative bromocriptine therapy. Clin Endocrinol. 1987;26(5):541–56.
13.
go back to reference Menucci M, Quinones-Hinojosa A, Burger P, Salvatori R. Effect of dopaminergic drug treatment on surgical findings in prolactinomas. Pituitary. 2011;14(1):68–74.PubMedPubMedCentral Menucci M, Quinones-Hinojosa A, Burger P, Salvatori R. Effect of dopaminergic drug treatment on surgical findings in prolactinomas. Pituitary. 2011;14(1):68–74.PubMedPubMedCentral
14.
go back to reference Landolt AM, Keller PJ, Froesch ER, Mueller J. Bromocriptine: does it jeopardise the result of later surgery for prolactinomas? Lancet. 1982;2(8299):657–8.PubMed Landolt AM, Keller PJ, Froesch ER, Mueller J. Bromocriptine: does it jeopardise the result of later surgery for prolactinomas? Lancet. 1982;2(8299):657–8.PubMed
15.
go back to reference Vale FL, Deukmedjian AR, Hann S, Shah V, Morrison AD. Medically treated prolactin-secreting pituitary adenomas: when should we operate? Br J Neurosurg. 2013;27(1):56–62.PubMed Vale FL, Deukmedjian AR, Hann S, Shah V, Morrison AD. Medically treated prolactin-secreting pituitary adenomas: when should we operate? Br J Neurosurg. 2013;27(1):56–62.PubMed
16.
go back to reference Oh MC, Aghi MK. Dopamine agonist-resistant prolactinomas. J Neurosurg. 2011;114(5):1369–79.PubMed Oh MC, Aghi MK. Dopamine agonist-resistant prolactinomas. J Neurosurg. 2011;114(5):1369–79.PubMed
17.
go back to reference Delgrange E, Duprez T, Maiter D. Influence of parasellar extension of macroprolactinomas defined by magnetic resonance imaging on their responsiveness to dopamine agonist therapy. Clin Endocrinol. 2006;64(4):456–62. Delgrange E, Duprez T, Maiter D. Influence of parasellar extension of macroprolactinomas defined by magnetic resonance imaging on their responsiveness to dopamine agonist therapy. Clin Endocrinol. 2006;64(4):456–62.
18.
go back to reference Vroonen L, Jaffrain-Rea ML, Petrossians P, Tamagno G, Chanson P, Vilar L, et al. Prolactinomas resistant to standard doses of cabergoline: a multicenter study of 92 patients. Eur J Endocrinol. 2012;167(5):651–62.PubMed Vroonen L, Jaffrain-Rea ML, Petrossians P, Tamagno G, Chanson P, Vilar L, et al. Prolactinomas resistant to standard doses of cabergoline: a multicenter study of 92 patients. Eur J Endocrinol. 2012;167(5):651–62.PubMed
19.
go back to reference Molitch ME. Management of medically refractory prolactinoma. J Neuro-Oncol. 2014;117(3):421–8. Molitch ME. Management of medically refractory prolactinoma. J Neuro-Oncol. 2014;117(3):421–8.
20.
go back to reference Delgrange E, Trouillas J, Maiter D, Donckier J, Tourniaire J. Sex-related difference in the growth of prolactinomas: a clinical and proliferation marker study. J Clin Endocrinol Metab. 1997;82(7):2102–7.PubMed Delgrange E, Trouillas J, Maiter D, Donckier J, Tourniaire J. Sex-related difference in the growth of prolactinomas: a clinical and proliferation marker study. J Clin Endocrinol Metab. 1997;82(7):2102–7.PubMed
21.
go back to reference Delgrange E, Sassolas G, Perrin G, Jan M, Trouillas J. Clinical and histological correlations in prolactinomas, with special reference to bromocriptine resistance. Acta Neurochir. 2005;147(7):751–7 discussion 7-8.PubMed Delgrange E, Sassolas G, Perrin G, Jan M, Trouillas J. Clinical and histological correlations in prolactinomas, with special reference to bromocriptine resistance. Acta Neurochir. 2005;147(7):751–7 discussion 7-8.PubMed
22.
go back to reference Alkabbani AG, Mon SY, Hatipoglu B, Kennedy L, Faiman C, Weil RJ, et al. Is a stable or decreasing prolactin level in a patient with prolactinoma a surrogate marker for lack of tumor growth? Pituitary. 2014;17(2):97–102.PubMed Alkabbani AG, Mon SY, Hatipoglu B, Kennedy L, Faiman C, Weil RJ, et al. Is a stable or decreasing prolactin level in a patient with prolactinoma a surrogate marker for lack of tumor growth? Pituitary. 2014;17(2):97–102.PubMed
23.
go back to reference Gonzaga MFM, de Castro LF, Naves LA, Mendonca JL, Oton de Lima B, Kessler I, et al. Prolactinomas Resistant to Treatment With Dopamine Agonists: Long-Term Follow-Up of Six Cases. Front Endocrinol (Lausanne). 2018;9:625. Gonzaga MFM, de Castro LF, Naves LA, Mendonca JL, Oton de Lima B, Kessler I, et al. Prolactinomas Resistant to Treatment With Dopamine Agonists: Long-Term Follow-Up of Six Cases. Front Endocrinol (Lausanne). 2018;9:625.
24.
go back to reference Ono M, Miki N, Kawamata T, Makino R, Amano K, Seki T, et al. Prospective study of high-dose cabergoline treatment of prolactinomas in 150 patients. J Clin Endocrinol Metab. 2008;93(12):4721–7.PubMed Ono M, Miki N, Kawamata T, Makino R, Amano K, Seki T, et al. Prospective study of high-dose cabergoline treatment of prolactinomas in 150 patients. J Clin Endocrinol Metab. 2008;93(12):4721–7.PubMed
25.
go back to reference Babey M, Sahli R, Vajtai I, Andres RH, Seiler RW. Pituitary surgery for small prolactinomas as an alternative to treatment with dopamine agonists. Pituitary. 2011;14(3):222–30.PubMed Babey M, Sahli R, Vajtai I, Andres RH, Seiler RW. Pituitary surgery for small prolactinomas as an alternative to treatment with dopamine agonists. Pituitary. 2011;14(3):222–30.PubMed
Metadata
Title
Predictors of dopamine agonist resistance in prolactinoma patients
Authors
Elle Vermeulen
Jean D’Haens
Tadeusz Stadnik
David Unuane
Kurt Barbe
Vera Van Velthoven
Sven Gläsker
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Endocrine Disorders / Issue 1/2020
Electronic ISSN: 1472-6823
DOI
https://doi.org/10.1186/s12902-020-0543-4

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