{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T15:56:40Z","timestamp":1780070200919,"version":"3.54.0"},"reference-count":43,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T00:00:00Z","timestamp":1624924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Prolactinomas represent a unique challenge for endocrinologists and neurosurgeons. Considering recent innovations in surgical practice, the authors aimed to investigate the best management for prolactinomas. Methods: A retrospective, cross-sectional and monocentric study was designed. Consecutive patients affected by prolactinomas were enrolled if treated with a first-line treatment with a dopamine agonist (DA) or trans-sphenoidal surgery (TSS). Patients carried giant prolactinomas, and those with a follow-up &lt;12 months were excluded. Results: Two hundred and fifty-nine patients were enrolled. The first treatment was DA for 140 patients and TS for 119 cases. One hundred and forty-six of 249 patients (58.6%) needed a second therapy. The mean follow-up was 102.2 months (12\u2013438 months). Surgery highly impacted on the cure rate\u2014in particular, in females (p = 0.0021) and in microprolactinomas (p = 0.0020). Considering the multivariate analysis, the female gender and surgical treatment in the course of the clinical history were the only independent positive predictors of a cure at the end of 5 years follow-up (p = 0.0016, p = 0.0005). The evaluation of serum prolactin (24 hours after TSS) revealed that 86.4% of patients with postoperative prolactin (PRL) \u226410 ng\/mL were cured at the end of the follow-up (p &lt; 0.0001). Conclusions: According to our experience, surgery allows a high cure rate of prolactinomas, particularly in females with microadenoma, with a good safety profile. TSS for prolactinomas should be considered as a concrete option, during the multidisciplinary evaluation, in centers of reference for pituitary diseases.<\/jats:p>","DOI":"10.3390\/cancers13133252","type":"journal-article","created":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T10:52:46Z","timestamp":1624963966000},"page":"3252","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Reappraising the Role of Trans-Sphenoidal Surgery in Prolactin-Secreting Pituitary Tumors"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2857-9096","authenticated-orcid":false,"given":"Pier Paolo","family":"Mattogno","sequence":"first","affiliation":[{"name":"Institute of Neurosurgery, Fondazione Policlinico Gemelli IRCCS, Universit\u00e0 Cattolica del Sacro Cuore-Roma, Largo A. Gemelli 8, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quintino Giorgio","family":"D\u2019Alessandris","sequence":"additional","affiliation":[{"name":"Institute of Neurosurgery, Fondazione Policlinico Gemelli IRCCS, Universit\u00e0 Cattolica del Sacro Cuore-Roma, Largo A. Gemelli 8, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Chiloiro","sequence":"additional","affiliation":[{"name":"Pituitary Unit, Department of Endocrinology and Metabolism, Fondazione Policlinico Gemelli IRCCS-Universit\u00e0 Cattolica del Sacro Cuore-Roma, Largo A. Gemelli 8, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Bianchi","sequence":"additional","affiliation":[{"name":"Pituitary Unit, Department of Endocrinology and Metabolism, Fondazione Policlinico Gemelli IRCCS-Universit\u00e0 Cattolica del Sacro Cuore-Roma, Largo A. Gemelli 8, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Giampietro","sequence":"additional","affiliation":[{"name":"Pituitary Unit, Department of Endocrinology and Metabolism, Fondazione Policlinico Gemelli IRCCS-Universit\u00e0 Cattolica del Sacro Cuore-Roma, Largo A. Gemelli 8, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Pontecorvi","sequence":"additional","affiliation":[{"name":"Pituitary Unit, Department of Endocrinology and Metabolism, Fondazione Policlinico Gemelli IRCCS-Universit\u00e0 Cattolica del Sacro Cuore-Roma, Largo A. Gemelli 8, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"De Marinis","sequence":"additional","affiliation":[{"name":"Pituitary Unit, Department of Endocrinology and Metabolism, Fondazione Policlinico Gemelli IRCCS-Universit\u00e0 Cattolica del Sacro Cuore-Roma, Largo A. Gemelli 8, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Olivi","sequence":"additional","affiliation":[{"name":"Institute of Neurosurgery, Fondazione Policlinico Gemelli IRCCS, Universit\u00e0 Cattolica del Sacro Cuore-Roma, Largo A. Gemelli 8, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmelo","family":"Anile","sequence":"additional","affiliation":[{"name":"Institute of Neurosurgery, Fondazione Policlinico Gemelli IRCCS, Universit\u00e0 Cattolica del Sacro Cuore-Roma, Largo A. Gemelli 8, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6463-055X","authenticated-orcid":false,"given":"Liverana","family":"Lauretti","sequence":"additional","affiliation":[{"name":"Institute of Neurosurgery, Fondazione Policlinico Gemelli IRCCS, Universit\u00e0 Cattolica del Sacro Cuore-Roma, Largo A. Gemelli 8, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1002\/cncr.20412","article-title":"The prevalence of pituitary adenomas: A systematic review","volume":"101","author":"Ezzat","year":"2004","journal-title":"Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1111\/j.1365-2265.2007.02905.x","article-title":"Predictors of remission of hyperprolactinaemia after long-term withdrawal of cabergoline therapy","volume":"673","author":"Colao","year":"2007","journal-title":"Clin. Endocrinol."},{"key":"ref_3","first-page":"1045","article-title":"Prolactinoma treatment status in the cabergoline era","volume":"39","author":"Watanabe","year":"2011","journal-title":"No Shinkei Geka."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"273","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":"ref_5","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1007\/s00701-016-2762-z","article-title":"Reasons and results of endoscopic surgery for prolactinomas: 142 surgical cases","volume":"158","author":"Akin","year":"2016","journal-title":"Acta Neurochir."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e5833","DOI":"10.1097\/MD.0000000000005833","article-title":"Surgical treatment for male prolactinoma: A retrospective study of 184 cases","volume":"96","author":"Song","year":"2017","journal-title":"Medicine"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1007\/s11102-010-0261-4","article-title":"Effect of dopaminergic drug treatment on surgical findings in prolactinomas","volume":"14","author":"Menucci","year":"2011","journal-title":"Pituitary"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e32","DOI":"10.1210\/clinem\/dgz144","article-title":"Surgery as a Viable Alternative First-Line Treatment for Prolactinoma Patients. A Systematic Review and Meta-Analysis","volume":"105","author":"Zandbergen","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.wneu.2018.06.015","article-title":"O-arm in Endonasal Endoscopic Cranial Base Surgery: Technical Note on Initial Feasibility","volume":"117","author":"Lauretti","year":"2018","journal-title":"World Neurosurg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1111\/cen.13355","article-title":"The incidence of anterior pituitary hormone deficiencies in patients with microprolactinoma and idiopathic hyperprolactinaemia","volume":"87","author":"Behan","year":"2017","journal-title":"Clin. Endocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1093\/neuros\/nyy385","article-title":"Endoscopic Transsphenoidal Surgery of Microprolactinomas: A Reappraisal of Cure Rate Based on Radiological Criteria","volume":"85","author":"Micko","year":"2019","journal-title":"Neurosurgery"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1056\/NEJMcp0912025","article-title":"Clinical practice. Prolactinomas","volume":"362","author":"Klibanski","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1007\/s40618-016-0483-z","article-title":"Recurrence of hyperprolactinemia following dopamine agonist withdrawal and possible predictive factors of recurrence in prolactinomas","volume":"29","author":"Sala","year":"2016","journal-title":"J. Endocrinol. Investig."},{"key":"ref_14","unstructured":"Melmed, S. (2017). Prolactinoma. The Pituitary, Elsevier. [4th ed.]."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1007\/s11102-017-0820-z","article-title":"Best candidates for dopamine agonist withdrawal in patients with prolactinomas","volume":"20","author":"Ji","year":"2017","journal-title":"Pituitary"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1007\/s11102-010-0283-y","article-title":"Pituitary Surgery for Small Prolactinomas as an Alternative to Treatment with Dopamine Agonists","volume":"14","author":"Babey","year":"2011","journal-title":"Pituitary"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s11102-005-5086-1","article-title":"Surgical Outcomes in Hyporesponsive Prolactinomas: Analysis of Patients with Resistance or Intolerance to Dopamine Agonists","volume":"8","author":"Hamilton","year":"2005","journal-title":"Pituitary"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1016\/j.clineuro.2013.02.016","article-title":"Transsphenoidal Microsurgical Results of Female Patients with Prolactinomas","volume":"115","author":"Ikeda","year":"2013","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1530\/EJE-07-0248","article-title":"Operative Treatment of Prolactinomas: Indications and Results in a Current Consecutive Series of 212 Patients","volume":"158","author":"Kreutzer","year":"2008","journal-title":"Eur. J. Endocrinol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.wneu.2012.06.024","article-title":"Pituitary Tumor Surgery: Review of 3004 Cases","volume":"79","year":"2013","journal-title":"World Neurosurg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s11102-013-0502-4","article-title":"Endoscopic Endonasal Approach for Pituitary Adenomas: A Series of 555 Patients","volume":"17","author":"Paluzzi","year":"2014","journal-title":"Pituitary"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1530\/EJE-11-1000","article-title":"Outcomes of Transsphenoidal Surgery in Prolactinomas: Improvement of Hormonal Control in Dopamine Agonist-Resistant Patients","volume":"166","author":"Primeau","year":"2012","journal-title":"Eur. J. Endocrinol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1530\/EJE-10-0961","article-title":"Surgical Outcomes and Prognostic Factors of Transsphenoidal Surgery for Prolactinoma in Men: A Single-Center Experience with 87 Consecutive Cases","volume":"164","author":"Qu","year":"2011","journal-title":"Eur. J. Endocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1210\/jc.2009-1191","article-title":"Prognostic Factors in Prolactin Pituitary Tumors: Clinical, Histological, and Molecular Data From a Series of 94 Patients With a Long Postoperative Follow-Up","volume":"95","author":"Raverot","year":"2010","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"532","DOI":"10.4103\/0028-3886.84332","article-title":"Microsurgical Management of Prolactinomas-Clinical and Hormonal Outcome in a Series of 172 Cases","volume":"59","author":"Sinha","year":"2011","journal-title":"Neurol. India"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"691","DOI":"10.3390\/medicina43090089","article-title":"Transsphenoidal Surgery for Prolactinomas: Results and Prognosis","volume":"43","author":"Rastenyte","year":"2007","journal-title":"Medicina"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1007\/s00701-012-1450-x","article-title":"Transsphenoidal Surgery for Microprolactinomas in Women: Results and Prognosis","volume":"154","author":"Tamasauskas","year":"2012","journal-title":"Acta Neurochir."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s12020-016-1115-2","article-title":"10-year follow-up study comparing primary medical vs. surgical therapy in women with prolactinomas","volume":"55","author":"Andereggen","year":"2017","journal-title":"Endocrine"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1080\/17446651.2018.1411798","article-title":"Medical versus surgical treatment of prolactinoma: An analysis of treatment outcomes","volume":"13","author":"Rutkowski","year":"2018","journal-title":"Expert Rev. Endocrinol. Metab."},{"key":"ref_30","first-page":"267","article-title":"Radically resected pituitary adenomas: Prognostic role of Ki 67 labeling index in a monocentric retrospective series and literature review","volume":"17","author":"Chiloiro","year":"2014","journal-title":"Pituitary"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1530\/EJE-15-0586","article-title":"Minichromosome Maintenance Protein 7 as Prognostic Marker of Tumor Aggressiveness in Pituitary Adenoma Patients","volume":"174","author":"Coli","year":"2016","journal-title":"Eur. J. Endocrinol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/S0895-3988(15)30112-4","article-title":"The Expression of Estrogen Receptor Subtypes in Prolactinomas and Their Relationship to Tumor Biological Behavior","volume":"28","author":"Li","year":"2015","journal-title":"Biomed. Environ. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1530\/EJE-11-0656","article-title":"Resistance to Dopamine Agonists in Prolactinoma Is Correlated with Reduction of Dopamine D2 Receptor Long Isoform mRNA Levels","volume":"166","author":"Shimazu","year":"2012","journal-title":"Eur. J. Endocrinol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1159\/000499382","article-title":"Clinical, Pathological, and Molecular Factors of Aggressiveness in Lactotroph Tumours","volume":"109","author":"Trouillas","year":"2019","journal-title":"Neuroendocrinology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1016\/0026-0495(82)90159-7","article-title":"Dopaminergic Mechanisms Regulating Prolactin Secretion in Patients With Prolactin-Secreting Pituitary Adenoma. Long-term Studies after Selective Transsphenoidal Surgery","volume":"31","author":"Barbarino","year":"1982","journal-title":"Metabolism"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1210\/jcem-47-5-1148","article-title":"Serum Prolactin Response to Thyrotropin-Releasing Hormone and Metoclopramide in Patients with Prolactin-Secreting Tumors Before and After Transsphenoidal Surgery","volume":"47","author":"Barbarino","year":"1978","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_37","first-page":"10","article-title":"Prolactin Dynamics in Patients with Non-Secretin Tumours of the Hypothalamic-Pituitary Region","volume":"110","author":"Barbarino","year":"1985","journal-title":"Acta Endocrinol."},{"key":"ref_38","first-page":"397","article-title":"Prolactin-secreting Pituitary Adenomas: Prolactin Dynamics Before and After Transsphenoidal Surgery","volume":"91","author":"Barbarino","year":"1979","journal-title":"Acta Endocrinol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/0026-0495(85)90138-6","article-title":"Evaluation of Dopaminergic Tone in Hyperprolactinemia. III. Thyroid-stimulating Hormone Response to Metoclopramide in Differential Diagnosis and Postoperative Follow-Up of Prolactinoma Patients","volume":"34","author":"Mancini","year":"1985","journal-title":"Metabolism"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1007\/s12020-017-1486-z","article-title":"Use of 111In-pentetreotide Scintigraphy for Diagnosis and Management of Resistant Macroprolactinoma","volume":"60","author":"Bima","year":"2018","journal-title":"Endocrine"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/s11102-008-0162-y","article-title":"Efficacy of the Combined Cabergoline and Octreotide Treatment in a Case of a Dopamine-Agonist Resistant Macroprolactinoma","volume":"14","author":"Fusco","year":"2011","journal-title":"Pituitary"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1227\/00006123-198905000-00013","article-title":"Prolactin-secreting Adenomas: Surgical Results and Long-Term Follow-Up","volume":"24","author":"Maira","year":"1989","journal-title":"Neurosurgery"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1017\/S0317167100030067","article-title":"Prolactin-secreting Adenomas--Surgical Results","volume":"17","author":"Maira","year":"1990","journal-title":"Can. J. Neurol. Sci."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/13\/3252\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:26:38Z","timestamp":1760163998000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/13\/3252"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,29]]},"references-count":43,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["cancers13133252"],"URL":"https:\/\/doi.org\/10.3390\/cancers13133252","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-283128\/v1","asserted-by":"object"}]},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,29]]}}}