{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T15:02:58Z","timestamp":1789311778325,"version":"build-2803163510"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T00:00:00Z","timestamp":1757376000000},"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>Purpose<\/jats:title><jats:p>To date, no specific criteria have been clearly established to predict the response to dopamine agonists (DA), and a universally accepted definition of DA resistance remains lacking. This study aimed to analyze the clinical, hormonal, and radiological characteristics of patients with prolactin (PRL)-secreting PitNETs, also known as pituitary adenomas, treated with DA, in order to identify potential predictive factors of hormonal and radiological response to medical therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This retrospective cohort study included 62 patients consecutively admitted to our institution over a 20-year period (2004 \u2013 2024). Seven patients underwent transsphenoidal surgery as first-line treatment before starting DA therapy. Demographic, clinical, hormonal, and radiological data were collected at diagnosis and during follow-up (6, 12, and 24 months, and at the last visit). DA resistance was defined as the failure to normalize PRL levels and to achieve at least a 50% reduction in the tumor\u2019s major diameter or volume.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The median age at diagnosis was 37 years (IQR 26.5 \u2013 45.3), with a male-to-female ratio of 1:1.7. Microprolactinomas were observed in 48.4% of patients. All patients were treated with cabergoline (median dose 1.0 mg\/week) and followed for a median of 84 months (IQR 35.3 \u2013 114.0). Macroprolactinomas were more frequent in males, who also showed higher baseline PRL levels. Early PRL response to DA treatment was a significant predictor of long-term hormonal response, independent of sex, age, and DA dosage (OR = 11.29; 95% CI 1.10 \u2013 60.74). Tumor response assessment revealed low agreement between classifications based on diameter versus volume reduction. Diameter-based evaluation was more effective in identifying clinical responders at 6 months and at final follow-up, while volumetric measurements provided greater accuracy at 12 and 24 months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Normalization of PRL levels is a practical and reliable predictor of treatment response. A combined radiological assessment using both tumor diameter and volume is advisable: diameter offers greater insight in the early stages, while volume becomes more informative in the mid- to long-term follow-up. In patients with persistently elevated PRL levels and lack of radiological response, alternative management strategies\u2014including surgical resection\u2014should be considered, especially in light of recent evidence supporting the cost-effectiveness of surgery in enclosed prolactinomas.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1664621","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T04:19:25Z","timestamp":1757391565000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Prolactin secreting pituitary neuroendocrine tumors treated by dopamine agonists: predictors of response"],"prefix":"10.3389","volume":"16","author":[{"given":"Chiara","family":"Mele","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Zavattaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Pitino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Romanisio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Ferrero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Sturnia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Catenazzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Rosmini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Baldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Marzullo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Aimaretti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"Prodam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Caputo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.19699","article-title":"Diagnosis and treatment of pituitary adenomas: A review","volume":"317","author":"Molitch","year":"2017","journal-title":"JAMA"},{"key":"B2","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s11102-005-5079-0","article-title":"The epidemiology of prolactinomas","volume":"8","author":"Ciccarelli","year":"2005","journal-title":"Pituitary"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2019.101290","article-title":"The epidemiology, diagnosis and treatment of Prolactinomas: The old and the new","volume":"33","author":"Chanson","year":"2019","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.82.7.4088","article-title":"Sex-related difference in the growth of prolactinomas: a clinical and proliferation marker study","volume":"82","author":"Delgrange","year":"1997","journal-title":"J Clin Endocrinol Metab"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/s0090-3019(03)00012-0","article-title":"Growth potential of prolactinomas in men: is it really different from women","volume":"59","author":"Nishioka","year":"2003","journal-title":"Surg Neurol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2018.00706","article-title":"Sex-related differences in lactotroph tumor aggressiveness are associated with a specific gene-expression signature and genome instability","volume":"9","author":"Wierinckx","year":"2018","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-1692","article-title":"Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline","volume":"96","author":"Melmed","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"key":"B8","doi-asserted-by":"publisher","first-page":"P1","DOI":"10.1530\/EJE-21-0977","article-title":"Italian Association of Clinical Endocrinologists (AME) and International Chapter of Clinical Endocrinology (ICCE). 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