title: Recurrence of hyperprolactinemia following dopamine agonist withdrawal and possible predictive factors of recurrence in prolactinomas.
abstract: BACKGROUND
  The optimal duration of cabergoline (CAB) treatment of prolactinomas that minimizes recurrences is not well established. 2011 Endocrine Society Guidelines suggested that withdrawal may be safely undertaken after 2 years in patients achieving normoprolactinemia and tumor reduction.
  
  
  METHODS
  We analyzed 74 patients (mean age = 46.9 ± 14.4, M/F = 19/55, macro/micro = 18/56) bearing a prolactinoma divided in 3 groups: group A (23) treated for 3 years, group B (23) for a period between 3 and 5 years, and group C (28) for a period >5 years. CAB therapy was interrupted according to Endocrine Society Guidelines. Prolactin (PRL) levels were measured 3, 6, 12 and 24 months after withdrawal. Recurrence was defined with PRL levels ≥30 ng/ml.
  
  
  RESULTS
  Groups did not differ in pretreatment PRL levels (123.2 ± 112.1, 120.9 ± 123.8, 176.6 ± 154.0), pituitary deficit (4, 17, 17 %), mean CAB weekly dose (0.7 ± 0.4, 0.6 ± 0.3, 0.7 ± 0.4) and PRL levels before withdrawal (17.1 ± 19.6, 11.4 ± 8.8, 13.8 ± 13.5). Recurrence occurred within 12 months in 34 patients (45.9 %), without significant differences among groups. Neuroradiological evaluation showed a significantly higher presence of macroadenoma in group C (13, 17 and 39 %, respectively). Recurrence rate of hyperprolactinemia did not depend on sex, tumor size or CAB dose but it was significantly correlated with PRL levels at diagnosis and before withdrawal (p = 0.03). Finally, patients with pituitary deficit at diagnosis showed a significantly higher recurrence rate (p = 0.03).
  
  
  CONCLUSIONS
  The study provides additional evidence that prolonging therapy for more than 3 years does not reduce recurrence rate. In particular, recurrence risk was similar in micro- and macroadenomas, and higher in patients with pituitary deficits at diagnosis.
authors.affiliation: Unit of Endocrinology and Diabetology - Pad. Granelli, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University of Milan, Via F. Sforza, 35, 20122, Milan, Italy. elisasala@yahoo.it.
authors.forename: E
authors.initials: E
authors.lastname: Sala
authors.affiliation: Unit of Endocrinology and Diabetology - Pad. Granelli, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University of Milan, Via F. Sforza, 35, 20122, Milan, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Bellaviti Buttoni
authors.affiliation: Unit of Endocrinology and Diabetology - Pad. Granelli, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University of Milan, Via F. Sforza, 35, 20122, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Malchiodi
authors.affiliation: Unit of Endocrinology and Diabetology - Pad. Granelli, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University of Milan, Via F. Sforza, 35, 20122, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Verrua
authors.affiliation: Unit of Endocrinology and Diabetology - Pad. Granelli, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University of Milan, Via F. Sforza, 35, 20122, Milan, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Carosi
authors.affiliation: Unit of Endocrinology and Diabetology - Pad. Granelli, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University of Milan, Via F. Sforza, 35, 20122, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Profka
authors.affiliation: Unit of Endocrinology and Diabetology - Pad. Granelli, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University of Milan, Via F. Sforza, 35, 20122, Milan, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Rodari
authors.affiliation: Unit of Endocrinology and Diabetology - Pad. Granelli, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University of Milan, Via F. Sforza, 35, 20122, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Filopanti
authors.affiliation: Unit of Endocrinology and Diabetology - Pad. Granelli, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University of Milan, Via F. Sforza, 35, 20122, Milan, Italy.|Unit of Endocrinology, San Carlo Borromeo Hospital, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Ferrante
authors.affiliation: Unit of Endocrinology and Diabetology - Pad. Granelli, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University of Milan, Via F. Sforza, 35, 20122, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Spada
authors.affiliation: Unit of Endocrinology and Diabetology - Pad. Granelli, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University of Milan, Via F. Sforza, 35, 20122, Milan, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Mantovani
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D000077465:Cabergoline; D018491:Dopamine Agonists / Q000627:therapeutic use*; D004873:Ergolines / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006966:Hyperprolactinemia / Q000175:diagnosis / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000209:etiology*; D010911:Pituitary Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D011379:Prognosis; D015175:Prolactinoma / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D014057:Tomography, X-Ray Computed / Q000379:methods; D028761:Withholding Treatment
chemical_list: D015415:Biomarkers; D018491:Dopamine Agonists; D004873:Ergolines; D000077465:Cabergoline
keywords: Dopamine agonist therapy; Hyperprolactinemia; Pituitary adenoma; Prolactinomas; Recurrence