J Neurol Surg B Skull Base
DOI: 10.1055/a-2212-0504
Original Article

Outcome Measures for Medical and Surgical Treatment of Prolactinomas. Is the Role of Surgery Underestimated?

Andrius Anuzis
1   Department of Neurosurgery, University of Colorado Anschutz Medical Center, Aurora, Colorado, United States
2   Department of Neurosurgery, King's College Hospital, London, United Kingdom
Kevin O. Lillehei
1   Department of Neurosurgery, University of Colorado Anschutz Medical Center, Aurora, Colorado, United States
› Author Affiliations


Introduction The first line treatment for prolactinomas is currently dopamine agonists (DAs). Medical management is prolonged, associated with side effects, financial, and psychological burdens. In dedicated centers, pituitary surgery is a low-risk alternative. We evaluated outcome measures of medical and surgical treatment, to assess, if the role of surgery is underestimated.

Methods We reviewed the charts of 4,660 pituitary patients, managed at the University of Colorado, from 2004 to 2019. The final analysis included 154 patients with prolactinomas, managed medically, and 120 patients, treated surgically. Primary outcome measures were percentage of tumor volume reduction and prolactin level (ng/mL). Mann–Whitney test was used for quantitative variables, contingency tables, and chi-square tests for qualitative variables. Statistical significance was set at p < 0.05.

Results DAs alone were more frequently used for microprolactinomas and Knosp grade 0 adenomas. Surgery was more often performed for macroprolactinomas, giant adenomas, tumors with suprasellar extension, mixed consistency, and sellar floor erosion. Among macroprolactinomas, mean tumor volume reduction after treatment with DAs alone, DAs and surgery, and surgery alone was 53.8, 94.9, and 94.1%, respectively. Prolactin levels after treatment were not significantly different. Continuous DA treatment was required in 94.3% patients in the medical group versus 39.6% in the surgical group.

Conclusions Surgery for macroprolactinomas achieved greater tumor volume reduction and dose reduction or discontinuation of DAs. Prolactin levels achieved did not differ significantly between the groups. Over 60% of patients, undergoing surgery, were able to discontinue DAs. The current treatment paradigm may underestimate the role of surgery in the management of prolactinomas.


Presented at NASBS 31st Annual Meeting in February 2022 as a Podium Presentation.

Ethical Approval

Ethical approval was waived by the Ethics Committee of the University of Colorado in view of the retrospective nature of the study and all the procedures being performed were part of the routine care.

Publication History

Received: 24 May 2023

Accepted: 10 November 2023

Accepted Manuscript online:
16 November 2023

Article published online:
13 December 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

  • References

  • 1 Quinones-Hinojosa A. Schmidek & Sweet Operative Neurosurgical Techniques. 6th ed.. Philadelphia: Saunders; 2012: 221-222
  • 2 Andereggen L, Frey J, Andres RH. et al. 10-year follow-up study comparing primary medical vs. surgical therapy in women with prolactinomas. Endocrine 2017; 55 (01) 223-230
  • 3 Donoho DA, Laws Jr ER. The role of surgery in the management of prolactinomas. Neurosurg Clin N Am 2019; 30 (04) 509-514
  • 4 Maiter D, Primeau V. 2012 update in the treatment of prolactinomas. Ann Endocrinol (Paris) 2012; 73 (02) 90-98
  • 5 Hamilton DK, Vance ML, Boulos PT, Laws ER. Surgical outcomes in hyporesponsive prolactinomas: analysis of patients with resistance or intolerance to dopamine agonists. Pituitary 2005; 8 (01) 53-60
  • 6 Ferrari CI, Abs R, Bevan JS. et al. Treatment of macroprolactinoma with cabergoline: a study of 85 patients. Clin Endocrinol (Oxf) 1997; 46 (04) 409-413
  • 7 Verhelst J, Abs R, Maiter D. et al. Cabergoline in the treatment of hyperprolactinemia: a study in 455 patients. J Clin Endocrinol Metab 1999; 84 (07) 2518-2522
  • 8 Losa M, Mortini P, Barzaghi R, Gioia L, Giovanelli M. Surgical treatment of prolactin-secreting pituitary adenomas: early results and long-term outcome. J Clin Endocrinol Metab 2002; 87 (07) 3180-3186
  • 9 Akin S, Isikay I, Soylemezoglu F, Yucel T, Gurlek A, Berker M. Reasons and results of endoscopic surgery for prolactinomas: 142 surgical cases. Acta Neurochir (Wien) 2016; 158 (05) 933-942
  • 10 Webster J, Piscitelli G, Polli A, Ferrari CI, Ismail I, Scanlon MF. Cabergoline Comparative Study Group. A comparison of cabergoline and bromocriptine in the treatment of hyperprolactinemic amenorrhea. N Engl J Med 1994; 331 (14) 904-909
  • 11 Pascal-Vigneron V, Weryha G, Bosc M, Leclere J. Hyperprolactinemic amenorrhea: treatment with cabergoline versus bromocriptine. Results of a national multicenter randomised double-blind study. Presse Med 1995; 24 (16) 753-757
  • 12 Colao A, Di Sarno A, Landi ML. et al. Macroprolactinoma shrinkage during cabergoline treatment is greater in naive patients than in patients pretreated with other dopamine agonists: a prospective study in 110 patients. J Clin Endocrinol Metab 2000; 85 (06) 2247-2252
  • 13 Lee Y, Ku CR, Kim E-H, Hong JW, Lee EJ, Kim SH. Early prediction of long-term response to cabergoline in patients with macroprolactinomas. Endocrinol Metab (Seoul) 2014; 29 (03) 280-292
  • 14 Molitch ME. Dopamine resistance of prolactinomas. Pituitary 2003; 6 (01) 19-27
  • 15 Molitch ME. Pharmacologic resistance in prolactinoma patients. Pituitary 2005; 8 (01) 43-52
  • 16 Di Sarno A, Landi ML, Cappabianca P. et al. Resistance to cabergoline as compared with bromocriptine in hyperprolactinemia: prevalence, clinical definition, and therapeutic strategy. J Clin Endocrinol Metab 2001; 86 (11) 5256-5261
  • 17 Vroonen L, Jaffrain-Rea ML, Petrossians P. et al. Prolactinomas resistant to standard doses of cabergoline: a multicenter study of 92 patients. Eur J Endocrinol 2012; 167 (05) 651-662
  • 18 Delgrange E, Daems T, Verhelst J, Abs R, Maiter D. Characterization of resistance to the prolactin-lowering effects of cabergoline in macroprolactinomas: a study in 122 patients. Eur J Endocrinol 2009; 160 (05) 747-752
  • 19 Biller BM, Molitch ME, Vance ML. et al. Treatment of prolactin-secreting macroadenomas with the once-weekly dopamine agonist cabergoline. J Clin Endocrinol Metab 1996; 81 (06) 2338-2343
  • 20 Zamanipoor Najafabadi AH, Zandbergen IM, de Vries F. et al. Surgery as a viable alternative first-line treatment for prolactinoma patients. A systematic review and meta-analysis. J Clin Endocrinol Metab 2020; 105 (03) e32-e41
  • 21 Tirosh A, Shimon I. Management of macroprolactinomas. Clin Diabetes Endocrinol 2015; 1: 5
  • 22 Biousse V, Newman NJ, Oyesiku NM. Precipitating factors in pituitary apoplexy. J Neurol Neurosurg Psychiatry 2001; 71 (04) 542-545
  • 23 Leong KS, Foy PM, Swift AC, Atkin SL, Hadden DR, MacFarlane IA. CSF rhinorrhoea following treatment with dopamine agonists for massive invasive prolactinomas. Clin Endocrinol (Oxf) 2000; 52 (01) 43-49
  • 24 Raverot G, Jacob M, Jouanneau E. et al. Secondary deterioration of visual field during cabergoline treatment for macroprolactinoma. Clin Endocrinol (Oxf) 2009; 70 (04) 588-592
  • 25 Jones SE, James RA, Hall K, Kendall-Taylor P. Optic chiasmal herniation—an under recognized complication of dopamine agonist therapy for macroprolactinoma. Clin Endocrinol (Oxf) 2000; 53 (04) 529-534
  • 26 Dekkers OM, Lagro J, Burman P, Jørgensen JO, Romijn JA, Pereira AM. Recurrence of hyperprolactinemia after withdrawal of dopamine agonists: systematic review and meta-analysis. J Clin Endocrinol Metab 2010; 95 (01) 43-51
  • 27 Menucci M, Quiñones-Hinojosa A, Burger P, Salvatori R. Effect of dopaminergic drug treatment on surgical findings in prolactinomas. Pituitary 2011; 14 (01) 68-74
  • 28 Vasilev V, Daly AF, Vroonen L, Zacharieva S, Beckers A. Resistant prolactinomas. J Endocrinol Invest 2011; 34 (04) 312-316
  • 29 Amar AP, Couldwell WT, Chen JC, Weiss MH. Predictive value of serum prolactin levels measured immediately after transsphenoidal surgery. J Neurosurg 2002; 97 (02) 307-314
  • 30 Kreutzer J, Buslei R, Wallaschofski H. et al. Operative treatment of prolactinomas: indications and results in a current consecutive series of 212 patients. Eur J Endocrinol 2008; 158 (01) 11-18
  • 31 Raverot G, Wierinckx A, Dantony E. et al; HYPOPRONOS. Prognostic factors in prolactin pituitary tumors: clinical, histological, and molecular data from a series of 94 patients with a long postoperative follow-up. J Clin Endocrinol Metab 2010; 95 (04) 1708-1716
  • 32 Molitch ME. Medical management of prolactin-secreting pituitary adenomas. Pituitary 2002; 5 (02) 55-65
  • 33 Hofstetter CP, Shin BJ, Mubita L. et al. Endoscopic endonasal transsphenoidal surgery for functional pituitary adenomas. Neurosurg Focus 2011; 30 (04) E10
  • 34 Babey M, Sahli R, Vajtai I, Andres RH, Seiler RW. Pituitary surgery for small prolactinomas as an alternative to treatment with dopamine agonists. Pituitary 2011; 14 (03) 222-230
  • 35 Ikeda H, Watanabe K, Tominaga T, Yoshimoto T. Transsphenoidal microsurgical results of female patients with prolactinomas. Clin Neurol Neurosurg 2013; 115 (09) 1621-1625
  • 36 Ma Q, Su J, Li Y. et al. The chance of permanent cure for micro- and macroprolactinomas, medication or surgery? A systematic review and meta-analysis. Front Endocrinol (Lausanne) 2018; 9 (09) 636
  • 37 Han Y-L, Chen D-M, Zhang C, Pan M, Yang X-P, Wu Y-G. Retrospective analysis of 52 patients with prolactinomas following endoscopic endonasal transsphenoidal surgery. Medicine (Baltimore) 2018; 97 (45) e13198
  • 38 Fraioli MF, Umana G, Pagano A, Fraioli B, Lunardi P. Prolactin secreting pituitary microadenoma: results of transsphenoidal surgery after medical therapy with dopamine agonist. J Craniofac Surg 2017; 28 (04) 992-994
  • 39 Zygourakis CC, Imber BS, Chen R. et al. Cost-effectiveness analysis of surgical versus medical treatment of prolactinomas. J Neurol Surg B Skull Base 2017; 78 (02) 125-131
  • 40 Mathieu D, Kotecha R, Sahgal A. et al. Stereotactic radiosurgery for secretory pituitary adenomas: systematic review and International Stereotactic Radiosurgery Society practice recommendations. J Neurosurg 2021; 136 (03) 801-812