Dopamine agonist resistant lactotroph adenoma [Neurosurgery Wiki]

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====== Dopamine agonist resistant lactotroph adenoma ======

{{ ::prolactinoma.jpeg?200|}}

While [[dopamine agonist]]s are a primary method of therapeutic treatment for [[Lactotroph adenoma]], the rate of resistance to these [[drug]]s continues to increase each year. 

Surgery is typically indicated for patients who are resistant to medical therapy or intolerant of its adverse side effects, or are experiencing progressive tumor growth. Surgical resection can also be considered as a primary treatment for those with smaller focal tumors where a biochemical cure can be expected as an alternative to lifelong dopamine agonist treatment. [[Stereotactic radiosurgery]] also serves as an option for those refractory to medical and surgical therapy
((Wong A, Eloy JA, Couldwell WT, Liu JK. Update on prolactinomas. Part 2:
Treatment and management strategies. J Clin Neurosci. 2015 Oct;22(10):1568-74.
doi: 10.1016/j.jocn.2015.03.059. Epub 2015 Aug 1. Review. PubMed PMID: 26243714.
)).

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Coopmans et al., reported a patient with an highly aggressive, dopamine-resistant prolactinoma, who only achieved biochemical and tumor control during [[pasireotide]] long-acting release (PAS-LAR) therapy , a second-generation [[somatostatin receptor ligand]] (SRL). Interestingly, cystic degeneration, tumor cell necrosis, or both was observed after PAS-LAR administration suggesting an antitumor effect. This case shows that PAS-LAR therapy holds clinical potential in selective aggressive, dopamine-resistant prolactinomas that express [[somatostatin receptor 5]] and appears to be a potential new treatment option before starting [[temozolomide]]. In addition, PAS-LAR therapy may induce cystic degeneration, tumor cell necrosis, or both in prolactinomas
((Coopmans EC, van Meyel SWF, Pieterman KJ, van Ipenburg JA, Hofland L, Donga E,
Daly AF, Beckers A, Van der Lely AJ, Neggers SJCMM. Excellent response to
pasireotide therapy in an aggressive and dopamine-resistant prolactinoma. Eur J
Endocrinol. 2019 Jun 1. pii: EJE-19-0279.R1. doi: 10.1530/EJE-19-0279. [Epub
ahead of print] PubMed PMID: 31167168.
)).
----
During previous long-term clinical investigations, Hu et al., from Department of Neurosurgery and Pituitary Tumor Center, The First Affiliated Hospital, Sun Yat-sen University, [[Guangzhou]], [[China]], found that partial resistant [[prolactinoma]]s exhibited significantly more fibrosis than did sensitive [[adenoma]]s, suggesting a role of fibrosis in their drug resistance. Furthermore, resistant adenomas with extensive fibrosis mainly express type I and type III [[collagen]]s. Since [[TGF-β1]] is the key factor in the initiation and development of tissue fibrosis, including in the [[pituitary]], in this study, they aimed to determine whether TGF-β1 mediated fibrosis in prolactinomas and whether fibrosis was related to prolactinoma drug resistance. Using [[immunochemistry]] and [[western blot]]ting, they found that the [[TGF-β1]]/[[Smad3]] [[signaling pathway]]-related proteins were elevated in resistant prolactinoma specimens with high degrees of fibrosis compared to levels in sensitive samples, suggesting that this pathway may play a role in prolactinoma fibrosis. [[In vitro]], TGF-β1 stimulation promoted collagen expression in normal [[HS27]] [[fibroblast]]s. Furthermore, the sensitivity of rat prolactinoma [[MMQ cell]]s to [[bromocriptine]] decreased when they were co-cultured with HS27 cells treated with TGF-β1. The TGF-β1/Smad3 signaling-specific inhibitor [[SB431542]] counteracted these effects, indicating that TGF-β1/Smad3-mediated fibrosis was involved in the drug-resistant mechanisms of [[prolactinoma]]s. These results indicate that [[SB431542]] may serve as a promising novel treatment for preventing fibrosis and further improving the drug resistance of [[prolactinoma]]s
((Hu B, Mao Z, Jiang X, He D, Wang Z, Wang X, Zhu Y, Wang H. Role of
[[TGF-β1]]/[[Smad3]]-mediated [[fibrosis]] in drug resistance mechanism of [[prolactinoma]].
Brain Res. 2018 Jul 26. pii: S0006-8993(18)30408-6. doi:
10.1016/j.brainres.2018.07.024. [Epub ahead of print] PubMed PMID: 30055965.
)).

===== References =====