Endocrine Abstracts

Background: Prolactinomas are the most frequent secreting pituitary adenomas encountered in the clinical setting. Cabergoline is considered the mainstay medical treatment and transsphenoidal surgery (TSS) is recommended for patients that are medically resistant to dopamine agonist therapy. Resistance to dopamine agonists is commonly defined as failure to normalize prolactin and less than 50% decrease in tumor diameter at a maximal labeled dose of 2.0 mg/week. Pasireotide LAR (PAS-LAR) is a 2nd generation multi-somatostatin receptor (SST) ligand, with particularly high affinity for SST₅ receptor.

Case presentation: A 61-year-old woman was referred for evaluation of a dopamine agonist-resistant prolactinoma. In 1993, she presented in a local hospital with only secondary amenorrhea since the age of 25. Her laboratory results showed hyperprolactinemia and her MRI revealed an invasive macro-adenoma in the anterior lobe of the pituitary. In the local hospital the patient received twice TSS and radiosurgery due to regrowth of the tumour with visual field defects on dopamine agonists. She was treated with cabergoline (weekly 3.0 mg), but eventually therapy failed and both hyperprolactinemia and clinically relevant tumor growth occurred again (227.36 ng per milliliter, tumour size 2549 mm³). We tried higher dosages of dopamine agonists (up to weekly 7 mg) as well as in combination with 1^st generation SST analogues. This again appeared to be unsuccessful (679.25 ng per milliliter, tumour size 3900 mm³). Before the use of temozolomide, we attempted PAS-LAR in combination with cabergoline to which our patient responded excellently (0.47 ng per milliliter, tumour size 1300 mm³). An important argument supporting to initiate PAS-LAR was the absence of visual field defects, which provided a window of opportunity. Immunohistochemistry showed membranous expression score of IRS 9 for SST₂ and IRS 12 for SST₅ and strong reactivity for prolactin. PAS-LAR markedly reduced the tumour size from 3900 mm³ before initiation to 1300 mm³ 24 months after treatment. Also, it lowered prolactin levels below upper limit of normal (43.9 ng per milliliter) within 2 months of administration to 0.47 ng per milliliter. Furthermore, T2-hyperintense signal and inhomogeneity on T1-signal intensity of the adenoma was observed after PAS-LAR treatment, indicating cystic degeneration/or tumour cell necrosis, which suggests an antitumour effect.

Conclusion: PAS-LAR therapy holds potential in dopamine agonist- and 1st generation SST analogue resistant prolactinomas that express high affinity for SST₅. Furthermore, switching to PAS-LAR can be considered in patients with an aggressive tumour as an in between treatment step before starting with Temozolomide.