Skip to main content
Log in

Prolactinoma management: predictors of remission and recurrence after dopamine agonists withdrawal

  • Published:
Pituitary Aims and scope Submit manuscript

Abstract

Objective

Prolactinomas are the most common functional pituitary tumour. Dopamine agonists (DA) are its principal treatment. The criteria that should guide therapy withdrawal and the factors that influence disease remission or relapse are not yet fully established. Our purpose is to evaluate the proportion of patients who attempted DA withdrawal, and to identify the factors that influence clinicians to try it. In addition, we aim to study the factors that are involved in prolactinoma remission/relapse after therapy withdrawal.

Methods

We retrospectively evaluated 142 patients with prolactinoma diagnosis who had been treated exclusively with DA. Firstly, the patients were divided in two groups, according to whether DA withdrawal had been attempted, or not, and the factors that might predict clinicians’ decision to discontinue the therapy were then analysed. Secondly, patients who attempted withdrawal were further divided into two subgroups, based on their remission or relapse status and predictors of remission were evaluated.

Results

DA withdrawal was attempted in 35.2% of our patients. Females, subjects with lower initial serum prolactin (PRL) levels, those with microadenomas and those with longer treatment duration all had a higher probability of seeing their therapy discontinued. In the withdrawal group, the remission rate was 72%. Macroprolactinomas relapse more often than microprolactinomas (p < 0.05). The recurrence group had higher median initial serum PRL levels and a lower mean duration of therapy, however these variables did not reach statistical significance.

Conclusion

We found a low percentage of attempt of withdrawal of DA therapy in the subjects with prolactinoma. Our data confirms that DA therapy can be discontinued with a high remission rate. Tumour size was the main variable that affected the withdrawal outcome in our patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Gillam MP, Molitch ME, Lombardi G, Colao A (2006) Advances in the treatment of prolactinomas. Endocr Rev 27(5):485–534. doi:10.1210/er.2005-9998

    Article  CAS  PubMed  Google Scholar 

  2. Kars M, Dekkers O, Pereira A, Romijn J (2010) Update in prolactinomas. Neth J Med 68(3):104–112

    CAS  PubMed  Google Scholar 

  3. Romijn JA (2014) Hyperprolactinemia and prolactinoma. Handb Clin Neurol 124:185–195. doi:10.1016/B978-0-444-59602-4.00013-7

    Article  PubMed  Google Scholar 

  4. Barber TM, Kenkre J, Garnett C, Scott RV, Byrne JV, Wass JA (2011) Recurrence of hyperprolactinaemia following discontinuation of dopamine agonist therapy in patients with prolactinoma occurs commonly especially in macroprolactinoma. Clin Endocrinol (Oxf) 75(6):819–824. doi:10.1111/j.1365-2265.2011.04136.x

    Article  CAS  Google Scholar 

  5. Kharlip J, Salvatori R, Yenokyan G, Wand G (2009) Recurrence of hyperprolactinemia after withdrawal of long-term cabergoline therapy. J Clin Endocrinol Metab 94(7):2428–2436

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Passos VQ, Souza JJ, Musolino NR, Bronstein MD (2002) Long-term follow-up of prolactinomas: normoprolactinemia after bromocriptine withdrawal. J Clin Endocrinol Metab 87(8):3578–3582

    Article  CAS  PubMed  Google Scholar 

  7. Huda MS, Athauda NB, Teh MM, Carroll PV, Powrie JK (2010) Factors determining the remission of microprolactinomas after dopamine agonist withdrawal. Clin Endocrinol (Oxf) 72(4):507–511. doi:10.1111/j.1365-2265.2009.03657.x

    Article  CAS  Google Scholar 

  8. Casanueva FF, Molitch ME, Schlechte JA, Abs R, Bonert V, Bronstein MD, Brue T, Cappabianca P, Colao A, Fahlbusch R (2006) Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas. Clin Endocrinol (Oxf) 65(2):265–273

    Article  Google Scholar 

  9. Melmed S, Casanueva FF, Hoffman AR, Kleinberg DL, Montori VM, Schlechte JA, Wass JA (2011) Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96(2):273–288

    Article  CAS  PubMed  Google Scholar 

  10. Hu J, Zheng X, Zhang W, Yang H (2015) Current drug withdrawal strategy in prolactinoma patients treated with cabergoline: a systematic review and meta-analysis. Pituitary 18(5):745–751. doi:10.1007/s11102-014-0617-2

    Article  CAS  PubMed  Google Scholar 

  11. Biswas M, Smith J, Jadon D, McEwan P, Rees DA, Evans LM, Scanlon MF, Davies JS (2005) Long-term remission following withdrawal of dopamine agonist therapy in subjects with microprolactinomas. Clin Endocrinol (Oxf) 63(1):26–31. doi:10.1111/j.1365-2265.2005.02293.x

    Article  CAS  Google Scholar 

  12. Colao A, Di Sarno A, Cappabianca P, Di Somma C, Pivonello R, Lombardi, G (2004) Withdrawal of long-term cabergoline therapy for tumoral and nontumoral hyperprolactinemia. Obstet Gynecol Surv 59(5):349–351

    Article  Google Scholar 

  13. Dekkers OM, Lagro J, Burman P, Jorgensen JO, Romijn JA, Pereira AM (2010) Recurrence of hyperprolactinemia after withdrawal of dopamine agonists: systematic review and meta-analysis. J Clin Endocrinol Metab 95(1):43–51. doi:10.1210/jc.2009-1238

    Article  CAS  PubMed  Google Scholar 

  14. Colao A, Lombardi G, Annunziato L (2000) Cabergoline. Expert Opin Pharmacother 1(3):555–574

    Article  CAS  PubMed  Google Scholar 

  15. Dogansen SC, Selcukbiricik OS, Tanrikulu S, Yarman S (2016) Withdrawal of dopamine agonist therapy in prolactinomas: in which patients and when? Pituitary 19(3):303–310

    Article  CAS  PubMed  Google Scholar 

  16. Colao A, Di Sarno A, Guerra E, Pivonello R, Cappabianca P, Caranci F, Elefante A, Cavallo LM, Briganti F, Cirillo S, Lombardi, G (2007) Predictors of remission of hyperprolactinaemia after long-term withdrawal of cabergoline therapy. Clin Endocrinol (Oxf) 67(3):426–433. doi:10.1111/j.1365-2265.2007.02905.x

    Article  CAS  Google Scholar 

  17. Anagnostis P, Adamidou F, Polyzos SA, Efstathiadou Z, Karathanassi E, Kita M (2012) Long term follow-up of patients with prolactinomas and outcome of dopamine agonist withdrawal: a single center experience. Pituitary 15(1):25–29. doi:10.1007/s11102-011-0303-6

    Article  PubMed  Google Scholar 

  18. Delgrange E, Trouillas J, Maiter D, Donckier J, Tourniaire J (1997) Sex-related difference in the growth of prolactinomas: a clinical and proliferation marker study 1. J Clin Endocrinol Metab 82(7):2102–2107

    CAS  PubMed  Google Scholar 

  19. Colao A, Sarno A, Cappabianca P, Briganti F, Pivonello R, Somma C, Faggiano A, Biondi B, Lombardi G (2003) Gender differences in the prevalence, clinical features and response to cabergoline in hyperprolactinemia. Eur J Endocrinol 148(3):325–331

    Article  CAS  PubMed  Google Scholar 

  20. Tindall GT, Kovacs K, Horvath E, Thorner MO (1982) Presence of human prolactin-producing adenomas and bromocriptine: a histological, immunocytochemical, ultrastructural, and morphometric study. J Clin Endocrinol Metab 55(6):1178–1183

    Article  CAS  PubMed  Google Scholar 

  21. Bassetti M, SPADA A, Pezzo G, Giannattasio G (1984) Bromocriptine treatment reduces the cell size in human macroprolactinomas: a morphometric study. J Clin Endocrinol Metab 58(2):268–273

    Article  CAS  PubMed  Google Scholar 

  22. Landolt AM, Osterwalder V (1984) perivascular fibrosis in prolactinomas: is it increased by bromocriptine. J Clin Endocrinol Metab 58(6):1179–1183

    Article  CAS  PubMed  Google Scholar 

  23. Jeffcoate W, Pound N, Sturrock N, Lambourne J (1996) Long-term follow-up of patients with hyperprolactinaemia. Clin Endocrinol (Oxf) 45(3):299–303

    Article  CAS  Google Scholar 

  24. Koppelman MC, Jaffe MJ, Rieth KG, Caruso RC, Loriaux DL (1984) Hyperprolactinemia, amenorrhea, and galactorrhea: a retrospective assessment of twenty-five cases. Ann Intern Med 100(1):115–121

    Article  CAS  PubMed  Google Scholar 

  25. Sisam DA, Sheehan JP, Sheeler LR (1987) The natural history of untreated microprolactinomas. Fertil Steril 48(1):67–71

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Margarida Teixeira.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Teixeira, M., Souteiro, P. & Carvalho, D. Prolactinoma management: predictors of remission and recurrence after dopamine agonists withdrawal. Pituitary 20, 464–470 (2017). https://doi.org/10.1007/s11102-017-0806-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11102-017-0806-x

Keywords

Navigation