{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T21:41:01Z","timestamp":1793742061570,"version":"4.6.1"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T00:00:00Z","timestamp":1693267200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Prolactinomas are the most frequent type of pituitary adenoma encountered in clinical practice. Dopamine agonists (DA) like cabergoline typically provide sign\/ symptom control, normalize prolactin levels and decrease tumor size in most patients. DA-resistant prolactinomas are infrequent and can occur in association with some genetic causes like MEN1 and pathogenic germline variants in the <jats:italic>AIP<\/jats:italic> gene (AIPvar).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We compared the clinical, radiological, and therapeutic characteristics of AIPvar-related prolactinomas (n=13) with unselected hospital-treated prolactinomas (\u201cunselected\u201d, n=41) and genetically-negative, DA-resistant prolactinomas (DA-resistant, n=39).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>AIPvar-related prolactinomas occurred at a significantly younger age than the unselected or DA-resistant prolactinomas (p&amp;lt;0.01). Males were more common in the AIPvar (75.0%) and DA- resistant (49.7%) versus unselected prolactinomas (9.8%; p&amp;lt;0.001). AIPvar prolactinomas exhibited significantly more frequent invasion than the other groups (p&amp;lt;0.001) and exhibited a trend to larger tumor diameter. The DA-resistant group had significantly higher prolactin levels at diagnosis than the AIPvar group (p&amp;lt;0.001). Maximum DA doses were significantly higher in the AIPvar and DA-resistant groups versus unselected. DA-induced macroadenoma shrinkage (&amp;gt;50%) occurred in 58.3% in the AIPvar group versus 4.2% in the DA-resistant group (p&amp;lt;0.01). Surgery was more frequent in the AIPvar and DA- resistant groups (43.8% and 61.5%, respectively) versus unselected (19.5%: p&amp;lt;0.01). Radiotherapy was used only in AIPvar (18.8%) and DA-resistant (25.6%) groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>AIPvar confer an aggressive phenotype in prolactinomas, with invasive tumors occurring at a younger age. These characteristics can help differentiate rare AIPvar related prolactinomas from DA-resistant, genetically-negative tumors.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2023.1242588","type":"journal-article","created":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T10:03:46Z","timestamp":1693389826000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["The clinical and therapeutic profiles of prolactinomas associated with germline pathogenic variants in the aryl hydrocarbon receptor interacting protein (AIP) 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