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Journal of Medical Case Reports
Published in: Journal of Medical Case Reports 1/2023

Open Access 01-12-2023 | Prolactinoma | Case report

Macroprolactinoma with secondary resistance to dopamine agonists: a case report and review of the literature 

Authors: Eng-Loon Tng, Ada Ee Der Teo, Aye Thida Aung

Published in: Journal of Medical Case Reports | Issue 1/2023

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Abstract

Background

Resistance to dopamine agonists is not uncommonly seen in prolactinomas. However, development of resistance to dopamine agonists after an initial period of robust treatment response is rare, and only 39 cases have been reported in the past four decades. We describe a Chinese man with this rare condition and explored the postulated mechanisms that may explain this phenomenon. We compiled similar cases that were previously reported and compared their etiology, progress, and response to treatment. On the basis of these cases, we derived a list of differential diagnoses to consider in patients with secondary resistance to dopamine agonists.

Case presentation

A 63-year-old Chinese man presented with blurred vision and was subsequently diagnosed with a macroprolactinoma. He had initial response to cabergoline but developed secondary resistance to it after 5 years. The prolactinoma continued to grow, and his serum prolactin remained markedly elevated despite adherence to escalating dosages of cabergoline up to 6 mg/week. The patient finally underwent transsphenoidal surgery and was found to have a sparsely granulated lactotroph tumor with Ki-67 index of 5%. Postoperatively, there was improvement in his serum prolactin level, although he still required treatment with cabergoline at 6 mg/week.

Conclusions

Surgery can facilitate disease control in patients with prolactinomas that develop secondary resistance to dopamine agonists. Malignant prolactinoma is an important differential diagnosis in this group of patients, especially when serum prolactin remains markedly elevated despite resolution or stability of the primary pituitary lesion, suggesting a metastatic source of prolactin secretion.
Literature
1.
Clayton RN. Sporadic pituitary tumours: from epidemiology to use of databases. Baillieres Best Pract Res Clin Endocrinol Metab. 1999;13(3):451–60.PubMedCrossRef
2.
Daly AF, Rixhon M, Adam C, Dempegioti A, Tichomirowa MA, Beckers A. High prevalence of pituitary adenomas: a cross-sectional study in the province of Liege. Belgium J Clin Endocrinol Metab. 2006;91(12):4769–75.PubMedCrossRef
3.
Fernandez A, Karavitaki N, Wass JAH. Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK). Clin Endocrinol (Oxf). 2010;72(3):377–82.PubMedCrossRef
4.
Bevan JS, Webster J, Burke CW, Scanlon MF. Dopamine agonists and pituitary tumor shrinkage. Endocr Rev. 1992;13(2):220–40.PubMedCrossRef
5.
Di Sarno A, Landi ML, Cappabianca P, Di Salle F, Rossi FW, Pivonello R, et al. Resistance to cabergoline as compared with bromocriptine in hyperprolactinemia: prevalence, clinical definition, and therapeutic strategy. J Clin Endocrinol Metab. 2001;86(11):5256–61.PubMedCrossRef
6.
7.
Delgrange E, Crabbé J, Donckier J. Late development of resistance to bromocriptine in a patient with macroprolactinoma. Horm Res Paediatr. 1998;49(5):250–3.CrossRef
8.
Sbardella E, Farah G, Fathelrahman A, Cudlip S, Ansorge O, Karavitaki N, et al. A macroprolactinoma becoming resistant to cabergoline and developing atypical pathology. Endocrinol Diabetes Metab Case Rep. 2016;2016:78.
9.
Scheithauer BW, Randall RV, Laws ER, Kovacs KT, Horvath E, Whitaker MD. Prolactin cell carcinoma of the pituitary. Clinicopathologic, immunohistochemical, and ultrastructural study of a case with cranial and extracranial metastases. Cancer. 1985;55(3):598–604.PubMedCrossRef
10.
Zornitzki T, Knobler H, Nass D, Hadani M, Shimon I. Increased MIB-1/Ki-67 Labeling index as a predictor of an aggressive course in a case of prolactinoma. Horm Res Paediatr. 2004;61(3):111–6.CrossRef
11.
Assies J, Verhoeff NPLG, Bosch DA, Hofland LJ. Intracranial dissemination of a macroprolactinoma. Clin Endocrinol (Oxf). 1993;38(5):539–46.PubMedCrossRef
12.
Kars M, Roelfsema F, Romijn JA, Pereira AM. Malignant prolactinoma: case report and review of the literature. Eur J Endocrinol. 2006;155(4):523–34.PubMedCrossRef
13.
Martin NA, Hales M, Wilson CB. Cerebellar metastasis from a prolactinoma during treatment with bromocriptine: Case report. J Neurosurg. 1981;55(4):615–9.PubMedCrossRef
14.
Petrossians P, De Herder W, Kwekkeboom D, Lamberigts G, Stevenaert A, Beckers A. Malignant Prolactinoma Discovered by D2 Receptor Imaging. J Clin Endocrinol Metab. 2000;85(1):398–401.PubMedCrossRef
15.
16.
Pernicone PJ, Scheithauer BW, Sebo TJ, Kovacs KT, Horvath E, Young WF, et al. Pituitary carcinoma: A clinicopathologic study of 15 cases. Cancer. 1997;79(4):804–12.PubMedCrossRef
17.
Mallea-Gil MS, Cristina C, Perez-Millan MI, Villafañe AMR, Ballarino C, Stalldecker G, et al. Invasive giant prolactinoma with loss of therapeutic response to cabergoline: expression of angiogenic markers. Endocr Pathol. 2009;20(1):35–40.PubMedCrossRef
18.
McCall D, Hunter SJ, Cooke RS, Herron B, Sheridan B, Atkinson AB. Unusual late development of dopamine agonist resistance in two women with hyperprolactinaemia associated with transition from micro to macroadenoma. Clin Endocrinol (Oxf). 2006;12:3.
19.
Shimazu S, Shimatsu A, Yamada S, Inoshita N, Nagamura Y, Usui T, et al. Resistance to dopamine agonists in prolactinoma is correlated with reduction of dopamine D2 receptor long isoform mRNA levels. Eur J Endocrinol. 2012;166(3):383–90.PubMedCrossRef
20.
Alberiche Ruano M, Boronat Cortés M, Ojeda Pino A, Rodriguez Perez C, Gracía Nuñez M, Marrero Arencibia D, et al. Acquired resistance to cabergoline: progression from initially responsive micro to macroprolactinoma. Pituitary. 2010;13(4):380–2.PubMedCrossRef
21.
Behan LA, Draman MS, Moran C, King T, Crowley RK, O’Sullivan EP, et al. Secondary resistance to cabergoline therapy in a macroprolactinoma: a case report and literature review. Pituitary. 2011;14(4):362–6.PubMedCrossRef
22.
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.PubMedCrossRef
23.
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.PubMedCrossRef
24.
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.PubMedCrossRef
25.
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.PubMedCrossRef
26.
27.
Dallabonzana D, Spelta B, Oppizzi G, Tonon C, Luccarelli G, Chiodini PG. Reenlargement of macroprolactinomas during bromocriptine treatment: report of two cases. J Endocrinol Invest. 1983;6:47–50.PubMedCrossRef
28.
Pivonello R, Ferone D, Lombardi G, Colao A, Lamberts SWJ, Hofland LJ. Novel insights in dopamine receptor physiology. Eur J Endocrinol. 2007;156:S13-21.PubMedCrossRef
29.
Pellegrini I, Rasolonjanahary R, Gunz G, Bertrand P, Delivet S, Jedynak CP, et al. Resistance to bromocriptine in prolactinomas. J Clin Endocrinol Metab. 1989;69(3):500–9.PubMedCrossRef
30.
Caccavelli L, Feron F, Morange I, Rouer E, Benarous R, Dewailly D, et al. Decreased expression of the two D2 dopamine receptor isoforms in bromocriptine-resistant prolactinomas. Neuroendocrinology. 1994;60(3):314–22.PubMedCrossRef
31.
Radl D, De Mei C, Chen E, Lee H, Borrelli E. Each individual isoform of the dopamine D2 receptor protects from lactotroph hyperplasia. Mol Endocrinol Baltim Md. 2013;27(6):953–65.CrossRef
32.
Kukstas LA, Domec C, Bascles L, Bonnet J, Verrier D, Israel JM, et al. Different expression of the two dopaminergic D2 receptors, D2415 and D2444, in two types of lactotroph each characterised by their response to dopamine, and modification of expression by sex steroids. Endocrinology. 1991;129(2):1101–3.PubMedCrossRef
33.
Wu ZB, Zheng WM, Su ZP, Chen Y, Wu JS, Wang CD, et al. Expression of D2RmRNA isoforms and ERmRNA isoforms in prolactinomas: correlation with the response to bromocriptine and with tumor biological behavior. J Neurooncol. 2010;99(1):25–32.PubMedCrossRef
34.
Gürlek A, Karavitaki N, Ansorge O, Wass JAH. What are the markers of aggressiveness in prolactinomas? Changes in cell biology, extracellular matrix components, angiogenesis and genetics. Eur J Endocrinol. 2007;156(2):143–53.PubMedCrossRef
35.
Freeman ME, Kanyicska B, Lerant A, Nagy G. Prolactin: structure, function, and regulation of secretion. Physiol Rev. 2000;80(4):1523–631.PubMedCrossRef
36.
37.
Auriemma RS, Galdiero M, Vitale P, Granieri L, Lo Calzo F, Salzano C, et al. Effect of chronic cabergoline treatment and testosterone replacement on metabolism in male patients with prolactinomas. Neuroendocrinology. 2015;101(1):66–81.PubMedCrossRef
38.
Gillam MP, Middler S, Freed DJ, Molitch ME. The novel use of very high doses of cabergoline and a combination of testosterone and an aromatase inhibitor in the treatment of a giant prolactinoma. J Clin Endocrinol Metab. 2002;87(10):4447–51.PubMedCrossRef
39.
Missale C, Losa M, Sigala S, Balsari A, Giovanelli M, Spano PF. Nerve growth factor controls proliferation and progression of human prolactinoma cell lines through an autocrine mechanism. Mol Endocrinol Baltim Md. 1996;10(3):272–85.
40.
Missale C, Boroni F, Losa M, Giovanelli M, Zanellato A, Dal Toso R, et al. Nerve growth factor suppresses the transforming phenotype of human prolactinomas. Proc Natl Acad Sci U S A. 1993;90(17):7961–5.PubMedPubMedCentralCrossRef
41.
Lin R, Canfield V, Levenson R. Dominant negative mutants of filamin A block cell surface expression of the D2 dopamine receptor. Pharmacology. 2002;66(4):173–81.PubMedCrossRef
42.
Peverelli E, Mantovani G, Vitali E, Elli FM, Olgiati L, Ferrero S, et al. Filamin-A is essential for dopamine d2 receptor expression and signaling in tumorous lactotrophs. J Clin Endocrinol Metab. 2012;97(3):967–77.PubMedCrossRef
43.
Hu B, Mao Z, Du Q, Jiang X, Wang Z, Xiao Z, et al. miR-93-5p targets Smad7 to regulate the transforming growth factor-β1/Smad3 pathway and mediate fibrosis in drug-resistant prolactinoma. Brain Res Bull. 2019;149:21–31.PubMedCrossRef
44.
Sabuncu T, Arikan E, Tasan E, Hatemi H. Comparison of the effects of cabergoline and bromocriptine on prolactin levels in hyperprolactinemic patients. Intern Med Tokyo Jpn. 2001;40(9):857–61.CrossRef
45.
Webster J, Piscitelli G, Polli A, Ferrari CI, Ismail I, Scanlon MF. A comparison of cabergoline and bromocriptine in the treatment of hyperprolactinemic amenorrhea. N Engl J Med. 1994;331(14):904–9.PubMedCrossRef
46.
Eguchi K, Kawamoto K, Uozumi T, Ito A, Arita K, Kurisu K. Effect of cabergoline, a dopamine agonist, on estrogen-induced rat pituitary tumors. In Vitro Culture Studies Endocr J. 1995;42(3):413–20.PubMed
47.
Verhelst J, Abs R, Maiter D, van den Bruel A, Vandeweghe M, Velkeniers B, et al. Cabergoline in the treatment of hyperprolactinemia: a study in 455 patients. J Clin Endocrinol Metab. 1999;84(7):2518–22.PubMedCrossRef
48.
Di Sarno A, Landi ML, Marzullo P, Di Somma C, Pivonello R, Cerbone G, et al. The effect of quinagolide and cabergoline, two selective dopamine receptor type 2 agonists, in the treatment of prolactinomas. Clin Endocrinol (Oxf). 2000;53(1):53–60.PubMedCrossRef
49.
50.
Kupersmith MJ, Kleinberg D, Warren FA, Budzilovitch G, Cooper P. Growth of prolactinoma despite lowering of serum prolactin by bromocriptine. Neurosurgery. 1989;24(3):417–23.PubMedCrossRef
51.
Brue T, Pellegrini I, Priou A, Morange I, Jaquet P. Prolactinomas and resistance to dopamine agonists. Horm Res. 1992;38(1–2):84–9.PubMedCrossRef
52.
Laboy-Ortiz IE, Velez-Maymí S, Hernán Martínez J, Trinidad R, Mangual M, Sanchez A, et al. Secondary resistance to dopamine agonist after thirteen months of successful treatment in a 42 years old man. Boletin Asoc Medica. 2016;108(10066):29–34.
53.
Astafeva LI, Kadashev BA, Trunin II. Rotin DL [Development of secondary resistance to dopamine agonists in a patient with giant prolactinoma]. Zh Vopr Neirokhir Im N N Burdenko. 2010;4:48–51.
Metadata
Title
Macroprolactinoma with secondary resistance to dopamine agonists: a case report and review of the literature 
Authors
Eng-Loon Tng
Ada Ee Der Teo
Aye Thida Aung
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Journal of Medical Case Reports / Issue 1/2023
Electronic ISSN: 1752-1947
DOI
https://doi.org/10.1186/s13256-023-03820-5

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