The Relevance of ACTH Monitoring during Surgical Management of Cushing's Disease

Introduction: The treatment of choice for ACTH-producing pituitary adenomas is complete removal using a transsphenoidal approach. However, even after gross total removal, high levels of ACTH and cortisol can be occasionally found in the first postoperative days. These hormonal findings could lead to a misdiagnosis of surgical failure with a later cortisol and ACTH drop. We propose an evaluation of intraoperative plasma ACTH and its correlation to hormonal postoperative findings to help improve the prediction of surgical success in patients with ACTH-producing adenomas.

Methods: Over 10 months, seven consecutive patients with ACTH-producing pituitary adenomas were analyzed. A detailed hormonal profile was performed preoperatively followed by at least one intraoperative plasma ACTH measurement during the endoscopic endonasal transsphenoidal resection of the tumor. ACTH and cortisol were evaluated postoperatively. The cases were divided according to tumor size, possible tumor invasion of adjacent structures, and surgical removal (intra- or extracapsular). All tumors were ACTH-producing adenomas, confirmed by pathology.

Results: Three patients had a microadenoma and four had a pituitary macroadenoma. One case was an invasive/recurrent adenoma. In all cases, a variable increase in the ACTH levels was observed intraoperatively. The most prominent ACTH increases were found in those cases that an extracapsular resection could not be performed. Minimal elevation in ACTH levels were seen in cases with extracapsular resection, and it correlated with a quick drop in cortisol down to undetectable levels.

Discussion: Low cortisol and ACTH levels in the first postoperative days are the ideal findings to predict successful resection of ACTH-producing pituitary adenomas. Occasionally, despite successful tumor removal, these expected values are not found in the early days after surgery. In this study, we found that ACTH levels can be considerably increased during surgery, especially in invasive tumors. This increase in ACTH levels would stimulate cortisol production and, consequently, would delay the expected cortisol “crash” postoperatively.

Conclusion: Intraoperative ACTH can be used as a baseline parameter to which postoperative ACTH and cortisol can be compared in the early postoperative period following surgical removal of ACTH-producing pituitary adenomas. A delay of the expected cortisol “crash” after surgery may not be always considered a surgical failure, but can be a predictable consequence of tumor manipulation and intraoperative hormonal release.