COVID19 infection and vaccination and the risk of pituitary apoplexy: an entangled yarn

Pituitary apoplexy (PA) has been increasingly reported in association with both infection from and vaccination for COVID19. Our aim was to analyse the available published cases and compare the clinical characteristics in the two groups (infection vs vaccination). We systematically reviewed the published literature for all cases of PA associated with COVID19 infection or vaccination. We also presented two cases managed at our Centre. Collectively, fortythree cases were analysed. Patients with PA after COVID19 vaccination (n = 7), compared with patients with PA after COVID19 infection (n = 36), were significantly younger (p = 0.009) and had a more abrupt onset of PA (p = 0.022), but showed a milder hormonal involvement (p = 0.008) and a lower rate of persistent hypopituitarism during follow-up (p = 0.001). Patients in the vaccination group did not have clinical risk factors for PA, although this difference did not reach statistical significance. PA associated with COVID19 is a rare but clinically significant entity, although pathophysiological details of this association are lacking. Given the significantly different clinical presentation, we could speculate that PA induced by COVID19 vaccination might represent a distinct clinical entity, with different pathophysiological mechanism, compared to PA from COVID19 infection.