SUN-066 Association Between Pre-operative Diagnosis of Cushing's Disease with ACTH Immunoreactivity: A Single-Institution Study

Abstract Disclosure: I. Cipollone: None. C. Malesky: None. V. Kantorovich: None. S. Zurek: None. P. Schwartz: None. Background: Cushing’s Disease (CD), caused by ACTH-secreting pituitary adenomas, associates with extended range of conditions, like hypertension, diabetes, osteoporosis, etc., that could generate severe morbidity. Accurate and timely pre-operative evaluation is essential for both appropriate managements, as well as prevention of potential post-operative complications like adrenal insufficiency. While proliferative and corticotrope markers assist in post-operative management, there is variability reported in the literature on their relationship to clinical symptoms1. This study evaluates the immunohistochemical profiles of pituitary adenomas in patients diagnosed with Cushing’s Disease, contributing to the understanding of pre-operative diagnostic challenges and their implications for patient management. Methods: A retrospective chart review was performed at a single urban hospital, involving patients who underwent transnasal endoscopic resection of a pituitary adenoma between April 2017 and September 2024. Pre-operative endocrinology evaluations were conducted to assess for thr presence of Cushing’s disease, and tumor characteristics were analyzed using immunohistochemical staining. Results: In this study, 19 patients diagnosed with Cushing's Disease displayed clear immunohistochemical staining patterns. The mean age of the participants was 53.3 years, with 79% being female. The average pre-operative BMI was 30.53, and 63% had a pre-operative diagnosis of diabetes mellitus. Of the 13 patients with ACTH-positive staining in their pituitary adenomas, 10 tumors (77%) showed diffuse staining, while 3 tumors (23%) exhibited sparse staining. Conclusions: Our findings indicate that pre-operative diagnosis of Cushing’s Disease is not consistently supported by immunohistochemical results. The distinction between focal and diffuse staining does not reliably correlate with the severity of the disease. Nonetheless, a majority of patients with a pre-operative diagnosis exhibited ACTH positive tumors with diffuse staining. Future research should explore the relationship between MIB1 labeling and ACTH staining distribution, use of PIT-1 to assess prevalence of ACTH negative/PIT-1 positive tumors among both clinical and subclinical CD cases, as well as assess the completeness of pre-operative evaluations and their impact on intervention timing and post-operative management. Presentation: Sunday, July 13, 2025