We describe the 20-year course of a 63-year-old male with a macroprolactinoma that acquired resistance to treatment and aggressive behavior after a 4-year successful treatment with cabergoline. He was submitted to multiple surgical resections by a skilled surgeon, fractionated radiotherapy and was eventually treated with temozolomide. After a first 6-month standard cycle, a relapse occurred and he was treated again successfully. Learning points: •• Prolactinomas are the most frequent type of pituitary adenoma. •• They usually have a benign course. •• In most cases dopamine-agonist drugs, mainly cabergoline, are first-line (and usually only) treatment. •• Occasionally prolactinomas can have or acquire resistance to treatment and/or aggressive behavior. •• Temozolomide (TMZ), an oral alkylating drug, can be effective in such aggressive tumors. •• Multimodal treatment (surgery, radiation, cabergoline and TMZ) is warranted in aggressive pituitary tumors. •• We describe here successful rechallenge with TMZ after relapse occurring 18 months after a first TMZ cycle.
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