Cerebrospinal Fluid Rhinorrhea after Medical Therapy for Prolactinoma: Systematic Review and Case Examples

Introduction: Prolactinomas are the most common hormone-secreting pituitary tumor. First-line treatment entails medical management with dopamine agonists (DAs) such as cabergoline or bromocriptine. Cerebrospinal fluid (CSF) leakage is an uncommon complication after DA treatment of prolactinomas and hypothesized to potentially be due to unplugging of osseous defects. It is important for treatment teams to recognize this potential complication. We hypothesized that systematic literature review and examination of cases at a tertiary care center may reveal important management considerations.

Methodology: A systematic review of PubMed, Web of Science, and EmBase was also conducted following PRISMA guidelines ([Fig. 1]). Data on incidence of dopamine agonist-induced CSF leakage, prolactinoma location and characteristics, and treatment details were collected. Two cases of CSF leak after DA treatment of prolactinoma were identified at Johns Hopkins (2022–2024).

Results: Systematic review yielded 39 case reports and case series and 20 larger patient sample size studies reporting CSF rhinorrhea post DA treatment of prolactinomas. From these studies a total of 112 patients with CSF leakage post DA were identified. In 43 patients there was reported CSF leakage in the context of tumor shrinkage, 66 patients with no documentation of tumor size comparison before or immediately after CSF-leak, and 3 patients with CSF-leakage in the context of no macroprolactinoma size change. There is a wide range of reported DA medication-induced CSF leakage incidence from 0 to 18.2% with one study reporting increased observations in giant and macro prolactinomas ([Table 1]). Most episodes of CSF leak occurred within 2 months of DA initiation with the longest time to CSF leak being over 5 years.

Case 1 is a 57-year-old female with a newly discovered skull base mass and elevated prolactin levels. She was prescribed cabergoline with no side effects for over 2 years. MRI imaging showed mild tumor growth from a baseline 3.5 cm × 2.5 cm to a 3.7 cm × 3.2 cm. Three years after cabergoline initiation, the patient endorsed right sided rhinorrhea that was positive for beta 2 transferrin. She underwent expanded endonasal approach debulking of the mass and CSF leak repair with a nasoseptal flap. Patient tolerated the procedure well and remained on cabergoline with well-managed prolactin levels and no further evidence of CSF leak.

Case 2 is a 50-year-old male with a macroprolactinoma treated for 2 months with cabergoline and developed new clear positional rhinorrhea. Physical exam confirmed slow clear drainage positive for beta 2 transferrin from the right nasal cavity with leaning forward. The patient underwent an endoscopic endonasal approach and nasoseptal flap reconstruction for CSF leak repair and debulking of the mass. Prolactin levels remained elevated thus the patient was re-prescribed cabergoline, which within 19 months lowered prolactin levels to single digits. There was no further evidence of CSF leak.

Conclusion: CSF leakage can complicate medical therapy of prolactinomas and should be considered in the differential diagnosis of new rhinorrhea by treatment teams throughout the treatment course with DA.

Publication History

Article published online:
07 February 2025