Pituitary Neuroendocrine Tumors (PitNET) are most frequently prolactinomas, which account for around half of all such tumors. The bulk of prolactinomas has typically been treated with Dopamine Agonists (DAs), with surgery being the last resort. The goal is to examine the historical and contemporary management of prolactinomas, with a focus on the effectiveness, safety, and potential future directions of current therapeutic modalities. This includes medical therapy with DAs, trans-sphenoidal surgery, and multimodality therapy for the treatment of aggressive prolactinomas and metastatic PitNETs. Since the 1970s, DAs have been the cornerstone of prolactinoma therapy, first with bromocriptine and more recently with cabergoline. In up to 85% of patients, cabergoline normalizes prolactin, and in up to 80% of cases, it shrinks tumors. Similar to cabergoline, the primary surgical excision of microprolactinomas and contained macroprolactinomas is undertaken by skilled pituitary neurosurgeons. Aggressive prolactinomas and metastatic PitNETS should be treated with a multimodal approach that includes surgery, radiation therapy, stereotactic radiosurgery when appropriate, and temozolomide. The majority of prolactinomas can still be successfully treated with DAs, but during the past decade or so, outcomes from transsphenoidal surgery under skilled surgeons have significantly improved. Surgery has a crucial role in the management of DA-resistant and aggressive prolactinomas, and it should be firmly considered as the first line of treatment, especially in the case of microprolactinomas, non-invasive macroprolactinomas, or prior to attempting pregnancy.
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