Delayed cerebral ischemia associated with surgery for pituitary macroadenomas that express elevated levels of PACAP

• Published in: Brain hemorrhages Vol. 4; no. 1; pp. 1 - 5
• Main Authors: Siler, Dominic A., Rosen, Kate U., Bowden, Stephen G., Powers, Andrew Y., Liu, Jesse J., Dogan, Aclan, Hinson, Holly E., Fleseriu, Maria, Woltjer, Randy L., Cetas, Justin S.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01-03-2023; KeAi Communications Co., Ltd
• Subjects: Delayed cerebral ischemia; PACAP; Pituitary macroadenoma; Vasospasm; Vasospasm; Delayed cerebral ischemia; Pituitary macroadenoma; PACAP
• ISSN: 2589-238X; 2589-238X
• DOI: 10.1016/j.hest.2022.05.003

Delayed cerebral ischemia (DCI) and cerebral vasospasm (VS) are rare but serious post-operative complications after surgery for pituitary macroadenomas; the mechanism of which are poorly understood. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a vasoactive neuropeptide expressed in pituitary adenomas and may play a role in DCI/VS. The aim of this case-control study was to investigate the association between tumor expression of PACAP and DCI/VS following pituitary surgery. Tumor tissue from five patients with DCI/VS following pituitary surgery and nine matched controls were evaluated for PACAP expression by immunohistochemistry. Nuclear PACAP expression was significantly elevated in patients with DCI/VS following pituitary surgery compared to controls (0.396 ± 0.0.16 a.u. vs 0.093 ± 0.04 a.u, p < 0.0001). There was a positive linear relationship between nuclear PACAP expression and pre-operative tumor volume (r2 = 0.41, p < 0.02) with a significant difference in slopes between the DCI/VS group compared to controls (y = x(5.0 × 10−3), r2 = 0.76 vs y = x(7.4 × 10−4), r2 = 0.07, p < 0.05). Elevated levels of tumor PACAP expression is associated with DCI/VS following pituitary surgery and may have a role in tumor growth. PACAP signaling may play a role the development of DCI, but further studies are needed.