Pituitary apoplexy in cushing's disease: a single center study and systematic literature review

Abstract

Introduction: Pituitary apoplexy (PA) in Cushing's disease (CD) is rare with data limited to case reports/series.

Methods: We retrospectively reviewed case records of PA in CD managed at our center from 1987 to 2023 and performed a systematic literature review.

Results: We identified 58 patients (44 females), including twelve from our center (12/315 CD, yielding a PA prevalence in CD of 3.8%) and forty six from systematic review. The median age at PA diagnosis was 35 years. The most common presentation was type A (79.3%) and symptom was headache (89.6%), with a median Pituitary Apoplexy Score (PAS) of 2. Median cortisol and ACTH levels were 24.9 µg/dl and 94.1 pg/ml, respectively. Apoplexy was the first manifestation of underlying CD in 55.2% of cases, with 31.1% (14/45) presenting with hypocortisolemia (serum cortisol ≤ 5.0 µg/dl), underscoring the importance of recognizing clinical signs/symptoms of hypercortisolism. The median largest tumor dimension was 1.7 cm (53/58 were macroadenomas). PA was managed surgically in 57.8% of cases, with the remainder conservatively managed. All five PA cases in CD with microadenoma achieved remission through conservative management, though two later relapsed. Among treatment-naïve CD patients with macroadenoma, PA-related neuro-deficit improvement was comparable between surgical and conservative groups. However, a greater proportion of surgically managed patients remained in remission longer (70% vs. 38.5%; p = 0.07), for an average of 31 vs. 10.5 months.

Conclusion: PA in CD is more commonly associated with macroadenomas, may present with hypocortisolemia, and surgical treatment tends towards higher and longer-lasting remission rates.

Keywords: Cushing’s disease; Macroadenoma; Pituitary apoplexy; Surgical management.