Recurrent pituitary apoplexy: experience from a national registry and review of the literature

Background: Pituitary apoplexy (PA) is a neuroendocrine emergency characterized by acute hemorrhage or infarction of a pituitary adenoma. While its initial presentation and management are well documented, data on recurrent PA remain scarce. Objectives: To determine the prevalence, clinical characteristics, and predictors of recurrent PA in a national cohort, and to contextualize findings through a structured review of the literature. Design: Multicenter retrospective cohort study complemented by a structured literature review. Methods: We analyzed 274 patients from the Spanish Pituitary Apoplexy Registry (2010–2023) with complete follow-up. Recurrent PA was defined as a new acute episode with radiological evidence of hemorrhage or infarction within a previously affected lesion. Clinical, radiological, and treatment-related variables were compared between recurrent and non-recurrent cases. A complementary literature review identified published reports of recurrence. Results: Recurrent PA occurred in 9 patients (3.3%), including 6 of 214 with nonfunctioning adenomas (2.8%) and 3 of 60 with functioning adenomas (5.0%). Compared with nonrecurrent cases, patients with recurrence had significantly larger tumors (median 35 vs 25 mm; p = 0.006), higher rates of cavernous sinus invasion (77.9% vs 37.3%; p = 0.006), and more frequent prior cabergoline therapy (33.3% vs 6.3%; p = 0.020). Median time to recurrence was 18 months (range, 2–108). The literature review identified 11 studies reporting recurrence rates of 2.6%–16.7%, with more consistent estimates (4%–9.6%) in larger series ( n ⩾ 50). All recurrent cases showed a favorable clinical course and recovery. Conclusion: Recurrent PA is uncommon, affecting approximately 3% of patients with a prior apoplexy episode. Given the low frequency of recurrence, the associated factors identified should be interpreted cautiously and considered primarily hypothesis-generating. The second episode was not more severe than the initial event, and the long-term prognosis was favorable. Trial registration: Not applicable.