PURPOSE: Although several reports have addressed cerebrospinal fluid (CSF) rhinorrhea following dopamine agonist (DA) therapy of macroprolactinomas, further study is warranted for this relatively uncommon entity. Toward this aim, our retrospective series and review of literature further clarifies recommendations in treatment of this rare problem. METHODS: We retrospectively reviewed all macroprolactinoma cases in our hospital for a 15-year period. Our systematic search of PubMed identified original articles and reviews of all macroprolactinoma cases with an associated medication-induced CSF leak. RESULTS: Five patients with drug-induced CSF leak were identified; four of these patients received cabergoline therapy an average of 6 weeks before the onset of rhinorrhea and then underwent surgical repair of the CSF leak. Of 35 published studies included, we identified 60 patients with medication-induced CSF leak. Medical therapy included bromocriptine in 34 patients, cabergoline in 21 patients, and use of both DAs in two patients. Three cases did include complete diagnostic and treatment data. Median time from initiation of the DA treatment to occurrence of rhinorrhea was 6 weeks. For CSF rhinorrhea, 49 patients underwent surgical repair (38 by the transnasal approach) and seven patients were treated nonoperatively. CONCLUSION: Baseline skull base erosion in macroprolactinomas in combination with subsequent tumor shrinkage induced by DA therapy may result in spontaneous CSF rhinorrhea. Therefore, such patients should be advised about and monitored for this potential setback. Once CSF leak is diagnosed, prompt treatment must be carried out to avoid infectious complications. Transnasal surgery appears the most effective therapeutic approach.

4th Department of Internal Medicine Haematology University Hospital Hradec Kralove Charles University Hradec Kralove Czech Republic

Department of Anatomy Faculty of Medicine in Hradec Kralove Charles University Hradec Kralove Czech Republic

Department of Neurosurgery University Hospital Hradec Kralove Charles University Hradec Kralove Czech Republic

Department of Otorhinolaryngology and Head and Neck Surgery University Hospital Hradec Kralove Charles University Hradec Kralove Czech Republic

Saint Alphonsus Neuroscience Institute Neurosurgery Boise ID USA

The Fingerland Department of Pathology University Hospital Hradec Kralove Charles University Hradec Kralove Czech Republic

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J Clin Neurosci. 2015 Oct;22(10):1568-74 PubMed

Cell. 1991 Jul 12;66(1):107-19 PubMed

Int Forum Allergy Rhinol. 2016 Jan;6(1):8-16 PubMed

Am J Med. 1987 Nov;83(5):995-1002 PubMed

Clin Diabetes Endocrinol. 2015 Jul 20;1:5 PubMed

J Clin Endocrinol Metab. 1997 Nov;82(11):3574-9 PubMed

Otolaryngol Head Neck Surg. 2004 Apr;130(4):443-8 PubMed

Laryngoscope. 2006 Oct;116(10):1882-6 PubMed

J Clin Endocrinol Metab. 2000 Aug;85(8):2931-5 PubMed

Clin Endocrinol (Oxf). 1994 Sep;41(3):359-64 PubMed

Acta Neurochir (Wien). 1989;96(3-4):107-13 PubMed

Cell. 2005 Feb 11;120(3):303-13 PubMed

Laryngoscope. 2005 Feb;115(2):205-12 PubMed

J Clin Endocrinol Metab. 2010 Apr;95(4):1708-16 PubMed

No Shinkei Geka. 1992 Oct;20(10):1091-5 PubMed

Endocr Rev. 1992 May;13(2):220-40 PubMed

Laryngoscope. 2004 Jun;114(6):969-74 PubMed

Eur J Endocrinol. 2008 Jan;158(1):11-8 PubMed

J Clin Endocrinol Metab. 2012 Oct;97(10):3412-3 PubMed

N Engl J Med. 1994 Oct 6;331(14):904-9 PubMed

Surg Neurol. 1982 Jul;18(1):61-3 PubMed

Int Forum Allergy Rhinol. 2012 Sep-Oct;2(5):397-401 PubMed

J Clin Neurosci. 2015 Oct;22(10):1562-7 PubMed

Endocr Pract. 2010 Jan-Feb;16(1):42-6 PubMed

Pituitary. 2004;7(2):83-7 PubMed

Clin Endocrinol (Oxf). 2009 Apr;70(4):588-92 PubMed

Ann Saudi Med. 1994 Jan;14(1):64-7 PubMed

Pituitary. 2005;8(2):147-54 PubMed

Laryngoscope Investig Otolaryngol. 2017 Apr 07;2(5):215-224 PubMed

Am J Rhinol Allergy. 2016 Nov 1;30(6):424-429 PubMed

Medicine (Baltimore). 2017 Jan;96(2):e5833 PubMed

Neurosurgery. 1982 Sep;11(3):395-401 PubMed

AMA Arch Otolaryngol. 1952 Jul;56(1):1-12 PubMed

Minim Invasive Neurosurg. 1998 Jun;41(2):66-73 PubMed

Melanoma Res. 2005 Oct;15(5):417-25 PubMed

J Endocrinol Invest. 2001 Mar;24(3):183-7 PubMed

Clin Endocrinol (Oxf). 2000 Jan;52(1):43-9 PubMed

Clin Endocrinol (Oxf). 2000 Oct;53(4):529-34 PubMed

Surg Neurol. 1989 Nov;32(5):346-9 PubMed

Surg Neurol. 2009 Nov;72(5):461-3; discussion 463 PubMed

J Clin Endocrinol Metab. 1992 Jul;75(1):275-80 PubMed

N Engl J Med. 2004 Mar 4;350(10):1054-7; author reply 1054-7 PubMed

Pituitary. 2002;5(4):243-6 PubMed

Clin Endocrinol (Oxf). 2013 Oct;79(4):447-56 PubMed

J Neurooncol. 2014 May;117(3):421-8 PubMed

Neurocirugia (Astur). 2011 Dec;22(6):558-61; discussion 561 PubMed

Arq Neuropsiquiatr. 2001 Jun;59(2-A):263-5 PubMed

Ear Nose Throat J. 1992 Jul;71(7):300-5 PubMed

Q J Med. 1990 Mar;74(275):227-38 PubMed

J Clin Endocrinol Metab. 2007 Oct;92(10):3829-35 PubMed

Endocrinol Metab Clin North Am. 2008 Mar;37(1):67-99, viii PubMed

Neurosurgery. 1997 Feb;40(2):225-36; discussion 236-7 PubMed

N Engl J Med. 2003 Nov 20;349(21):2035-41 PubMed

Neurosurg Focus. 2010 Oct;29(4):E4 PubMed

Clin Endocrinol (Oxf). 2000 Jul;53(1):53-60 PubMed

Nat Med. 1998 Aug;4(8):909-14 PubMed

Neurosurg Rev. 2007 Jan;30(1):78-82; discussion 82 PubMed

J Clin Invest. 2004 Sep;114(5):623-33 PubMed

Neurology. 1985 Aug;35(8):1193-5 PubMed

Brain Pathol. 2011 Sep;21(5):533-43 PubMed

Surg Neurol. 1992 Oct;38(4):321 PubMed

N Engl J Med. 1979 Jun 14;300(24):1391 PubMed

J Clin Endocrinol Metab. 2015 Apr;100(4):1699-708 PubMed

Eur J Endocrinol. 2007 Oct;157(4):371-82 PubMed

J Neurol Surg A Cent Eur Neurosurg. 2013 Dec;74 Suppl 1:e50-3 PubMed

Acta Clin Belg. 2009 Sep-Oct;64(5):457 PubMed

N Engl J Med. 1982 Jan 21;306(3):178 PubMed

Hum Pathol. 2014 Jan;45(1):71-7 PubMed

Acta Endocrinol (Copenh). 1983 Aug;103(4):457-60 PubMed

J Clin Neurosci. 2004 Nov;11(8):825-8 PubMed

Am J Pathol. 2003 May;162(5):1503-13 PubMed

Pituitary. 2014 Apr;17(2):97-102 PubMed

Cancer Res. 2002 Mar 1;62(5):1326-9 PubMed

J Clin Endocrinol Metab. 2008 Dec;93(12):4721-7 PubMed

AJNR Am J Neuroradiol. 2000 Feb;21(2):337-42 PubMed

Neurosurg Focus. 2012 Jun;32(6):E2 PubMed

J Clin Endocrinol Metab. 1985 Apr;60(4):698-705 PubMed

J Clin Endocrinol Metab. 2011 Feb;96(2):273-88 PubMed

Am J Surg Pathol. 2011 Aug;35(8):1204-13 PubMed

Clin Endocrinol (Oxf). 2003 May;58(5):662-70 PubMed

Surg Neurol. 1994 Jun;41(6):486-9 PubMed

Eur J Endocrinol. 2013 Nov 22;170(1):31-8 PubMed

J Hum Reprod Sci. 2011 May;4(2):104-5 PubMed

Cell. 2006 Jan 27;124(2):263-6 PubMed

Eur J Endocrinol. 2014 Jun;170(6):R213-27 PubMed

Neurosurg Focus. 2012 Jun;32(6):E7 PubMed

Aust N Z J Med. 2000 Jun;30(3):399-400 PubMed

J Neurosurg. 2002 Aug;97(2):299-306 PubMed

Laryngoscope. 2004 Jun;114(6):991-9 PubMed

Ann Endocrinol (Paris). 1994;54(5):347-51 PubMed

J Clin Endocrinol Metab. 1999 Jul;84(7):2518-22 PubMed

Mod Pathol. 2002 Dec;15(12):1357-65 PubMed

Neurology. 1984 Jan;34(1):111-3 PubMed

J Endocrinol Invest. 2006 Dec;29(11):1001-5 PubMed

Clin Endocrinol (Oxf). 1985 May;22(5):573-81 PubMed

Curr Opin Otolaryngol Head Neck Surg. 2015 Feb;23(1):78-82 PubMed