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Recurrence of hyperprolactinemia following dopamine agonist withdrawal and possible predictive factors of recurrence in prolactinomas

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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.

Materials

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.

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References

  1. Faglia G (1991) Should dopamine agonist treatment for prolactinomas be lifelong. Clin Endocrinol Oxf 34:173–174

    Article  CAS  PubMed  Google Scholar 

  2. Vitale G, Di Sarno A, Rota F, Lombardi G, Colao A (2003) When can we stop cabergoline treatment in prolactinomas? Curr Opin Endocrinol Diabetes 10:259–264

    Article  CAS  Google Scholar 

  3. Dekkers OM, Lagro J, Burman P, Jørgensen JO, Romijn JA, Pereira AM (2010) Recurrence of hyperprolactinemia after withdrawal of dopamine agonists: systematic review and meta-analysis. J Clin Endocrinol Metab 95:43–51

    Article  CAS  PubMed  Google Scholar 

  4. Ogilvie CM, Milsom SR (2011) Dopamine agonists in the treatment of prolactinoma: are they still first choice? Intern Med J 41:156–161

    Article  CAS  PubMed  Google Scholar 

  5. Mancini T, Casanueva FF, Giustina A (2008) Hyperprolactinemia and prolactinomas. Endocrinol Metab Clin North Am 37:67–99

    Article  CAS  PubMed  Google Scholar 

  6. Kars M, Dekkers OM, Pereira AM, Romijn JA (2010) Update in prolactinomas. Neth J Med 68:104–112

    CAS  PubMed  Google Scholar 

  7. Casanueva FF, Molitch ME, Schlechte JA, Abs R, Bonert V, Bronstein MD, Brue T, Cappabianca P, Colao A, Fahlbusch R, Fideleff H, Hadani M, Kelly P, Kleinberg D, Laws E, Marek J, Scanlon M, Sobrinho LG, Wass JA, Giustina A (2006) Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas. Clin Endocrinol 65:265–273

    Article  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  9. 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 63:26–31

    Article  CAS  PubMed  Google Scholar 

  10. 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 hyperprolactinemia after long-term withdrawal of cabergoline therapy. Clin Endocrinol Oxf 67:426–433

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. 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 75:819–824

    Article  CAS  PubMed  Google Scholar 

  13. 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 15:25–29

    Article  PubMed  Google Scholar 

  14. Colao A, Di Sarno A, Cappabianca P, Di Somma C, Pivonello R, Lombardi G (2003) Withdrawal of long-term cabergoline therapy for tumoural and nontumoural hyperprolactinemia. N Engl J Med 349:2023–2033

    Article  CAS  PubMed  Google Scholar 

  15. Mehmet S, Powrie JK (2003) A survey of dopamine agonist withdrawal policy in UK endocrinologists treating patients with prolactinomas. Clin Endocrinol Oxf 58:111–113

    Article  CAS  PubMed  Google Scholar 

  16. Wong A, Eloy JA, Couldwell WT, Liu JK (2015) Update on prolactinomas. Part 1: clinical manifestations and diagnostic challenges. J Clin Neurosci 22:1562–1567

    Article  PubMed  Google Scholar 

  17. Bogazzi F, Buralli S, Manetti L, Raffaelli V, Cigni T, Lombardi M, Boresi F, Taddei S, Salvetti A, Martino E (2008) Treatment with low doses of cabergoline is not associated with increased prevalence of cardiac valve regurgitation in patients with hyperprolactinaemia. Int J Clin Pract 62:1864–1869

    Article  CAS  PubMed  Google Scholar 

  18. Vallette S, Serri K, Serri O (2010) Cabergoline therapy for prolactinomas: is valvular heart disease a real safety concern? Expert Rev Cardiovasc Ther 8:49–54

    Article  CAS  PubMed  Google Scholar 

  19. Vallette S, Serri K, Rivera J, Santagata P, Delorme S, Garfield N, Kahtani N, Beauregard H, Aris-Jilwan N, Houde G, Serri O (2009) Long-term cabergoline therapy is not associated with valvular heart disease in patients with prolactinomas. Pituitary 12:153–157

    Article  CAS  PubMed  Google Scholar 

  20. Di Sarno A, Landi ML, Cappabianca P, Di Salle F, Rossi FW, Pivonello R, Di Somma C, Faggiano A, Lombardi G, Colao A (2001) Resistance to cabergoline as compared with bromocriptine in hyperprolactinemia: prevalence, clinical definition, and therapeutic strategy. J Clin Endocrinol Metab 86:5256–5261

    Article  CAS  PubMed  Google Scholar 

  21. Swords FM, Monson JP, Besser GM, Chew SL, Drake WM, Grossman AB, Plowman PN (2009) Gamma knife radiosurgery: a safe and effective salvage treatment for pituitary tumours not controlled despite conventional radiotherapy. Eur J Endocrinol 161:819–828

    Article  CAS  PubMed  Google Scholar 

  22. Huda MS, Athauda NB, Teh MM, Carroll PV, Powrie JK (2010) Factors determining the remission of microprolactinomas after dopamine agonist withdrawal. Clin Endocrinol (Oxf) 72:507–511

    Article  CAS  Google Scholar 

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Funding

This work was supported by Grant AIRC (Associazione Italiana Ricerca Cancro) to G.M. (IG 2014-15507) and Ricerca Corrente Funds from the Italian Ministry of Health.

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Authors and Affiliations

  1. 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

    E. Sala, P. Bellaviti Buttoni, E. Malchiodi, E. Verrua, G. Carosi, E. Profka, G. Rodari, M. Filopanti, E. Ferrante, A. Spada & G. Mantovani

  2. Unit of Endocrinology, San Carlo Borromeo Hospital, Milan, Italy

    E. Ferrante

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  1. E. Sala
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Correspondence to E. Sala.

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For this type of study formal consent is not required.

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In this retrospective study we collected data from medical reports, a written informed consent was obtained from each subject.

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Sala, E., Bellaviti Buttoni, P., Malchiodi, E. et al. Recurrence of hyperprolactinemia following dopamine agonist withdrawal and possible predictive factors of recurrence in prolactinomas. J Endocrinol Invest 39, 1377–1382 (2016). https://doi.org/10.1007/s40618-016-0483-z

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  • DOI: https://doi.org/10.1007/s40618-016-0483-z

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