Excellent response to pasireotide therapy in an aggressive and dopamine-resistant prolactinoma

in European Journal of Endocrinology
Correspondence should be addressed to E C Coopmans; Email: e.coopmans@erasmusmc.nl

*(E C Coopmans and S W F van Meyel contributed equally to this work)

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Prolactinomas are the most commonly encountered pituitary adenomas in the clinical setting. While most can be controlled by dopamine agonists, a subset of prolactinomas are dopamine-resistant and very aggressive. In such tumors, the treatment of choice is neurosurgery and radiotherapy, with or without temozolomide. Here, we report 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 (SST) receptor subtype 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.

 

     European Society of Endocrinology

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    Following first pituitary surgery. Immunohistochemistry for prolactin (A) showing strong expression of prolactin in most lesional cells, Ki-67 (Mib-1) (B) showing staining in 5–10% of the lesional cells without overexpression of p53 (C). Immunohistochemistry for SST2a receptor (D) showing membranous staining IRS 9, SST5 receptor (E) with IRS 12 after first surgery. IRS, immunoreactivity score.

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    Prolactin levels in response to different medical therapies during the academic clinical follow-up of the proband. Time (months) = 0 represents the time point of the referral to our institution. Data are shown until 60 months. CAB, cabergoline; LAN, lanreotide autogel; ng/mL, nanogram per milliliter; PAS-LAR, pasireotide long-acting release; ULN, upper limit of normal; wk, week. A full colour version of this figure is available at https://doi.org/10.1530/EJE-19-0279.

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    MRI scans showing T1- and T2-signal intensity, and tumor shrinkage during treatment with PAS-LAR in combination with low-dose cabergoline. Gadolinium-enhanced T1 and T2-weighted MRI scans obtained before initiation of PAS-LAR therapy, showing a large prolactinoma (left scan, tumor marked in red) during 5, 13 and 23 months of treatment, with marked reduction of the mass (second, third and fourth scan, tumor marked in red). Both visual assessment and the quantification of the T2-weighted signal by ROI measurement of the adenoma shows a higher T2-signal intensity during PAS-LAR treatment. PAS-LAR, pasireotide long-acting release; ROI, region of interest.

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