Endocrine Abstracts

Objective: Macroprolactinomas (MPRL) may result in spontaneous or dopamine-agonist-induced CSF rhinorrhoea. The incidence of, and mechanisms underlying this phenomenon are poorly understood. In this study, we aimed to determine the incidence of non-surgical (spontaneous and dopamine-agonist-induced) rhinorrhoea, and to identify biochemical, radiological and histopathological factors associated with this phenomenon.

Methods: We retrospectively reviewed MPRL patients (n=114) in comparison with patients with non-functioning pituitary adenoma (NFA) (n=180) seen over a 19-year period (1985–2004). Incidence of CSF rhinorrhoea, clinical factors predictive of leakage, and differential expression of candidate markers of invasiveness were assessed.

Results: Non-surgical CSF rhinorrhoea occurred in 8.7% of MPRLs (10/114) (2.6% spontaneous (3/114) and 6.1% dopamine-agonist-induced (7/114)), whereas no NFAs developed non-surgical rhinorrhoea. There was a clear male preponderance in MPRLs with CSF rhinorrhoea (M:F, 9:1, P=0.008). Dopamine-agonist resistance was more frequent in MPRLs with CSF rhinorrhoea versus MPRL without rhinorrhoea (30% (n=10) vs. 5% (n=104) P=0.003). Baseline prolactin levels, the rate of prolactin decline in response to dopamine-agonists and tumour volume at diagnosis did not predict CSF rhinorrhoea. Candidate markers of invasiveness, specifically, the protease-activated receptor1 (PAR1) and E-cadherin expression scores and tumour macrophage density were not significantly different among MPRLwith CSF rhinorrhoea (n=6), MPRL without CSF rhinorrhoea (n=9) and NFAs (n=9). All tumours studied for these specific markers were typical adenomas according to the WHO classification.

Conclusions: The incidence of non-surgical CSF rhinorrhoea in MPRL patients (8.7%) is higher then expected. Dopamine-agonist resistance is commoner in MPRLs developing CSF rhinorrhoea; however, whether this is a mechanistic relationship requires further study. PAR1 and e-cadherin expression and the extent of macrophage infiltration do not distinguish tumours with rhinorrhoea from those without CSF rhinorrhoea.