Cavernous Sinus Exploration in Cushing’s Disease: Indications and Outcomes

Introduction: Microscopic and macroscopic cavernous sinus invasion by adrenocorticotropic hormone (ACTH) secreting adenomas is associated with surgical failures and recurrence of Cushing’s disease (CD). The adenoma will often invade the medial wall of the sinus without extending further into the cavernous sinus compartments, allowing gross total resection of the involved medial wall. It is crucial to identify the extent of cavernous sinus invasion during transsphenoidal surgery (TSS) to attempt potential gross total resection of the ACTH secreting adenomas in CD. Additionally, it is necessary to identify when gross total resection is not feasible to initiate early adjuvant sellar/parasellar radiation. Here, we present our experience with the indications, intraoperative findings, and outcomes of cavernous sinus exploration during TSS for CD.

Methods: Between September 2012 and 2019, a total of 255 patients underwent transsphenoidal surgery (TSS) performed by author P.C. for suspected CD under a current clinical trial (NCT00060541). The patients underwent sublabial TSS with wide sellar and parasellar exposure, pseudocapsule-based adenectomy, exploration of the cavernous sinus, and resection of the medial wall of the cavernous sinus as described by Edward H. Oldfield (Figs.1 and 2).

Results: The cavernous sinus was explored in 34 patients (22 females) with a median age of 27 years. Preoperative MRI demonstrated distinct cavernous sinus invasion in 10 (29%) patients. In the remainder, the cavernous sinus was explored as a result of intraoperative findings. The adenoma was found to be adherent to the medial wall in 7 (21%) with frank invasion of the medial wall discovered in the rest (n = 27). In 15 surgeries, a gross total resection including the involved medial wall of the cavernous sinus was noted by the surgeon and the patients were in endocrinologic remission postoperatively. No further adjuvant radiation was recommended based on intraoperative findings. However, two of these patients recurred at 3 and 4 years postoperatively, respectively. In 19 (56%) patients, adjuvant radiation therapy was recommended as a result of these intraoperative findings—free tumor within the cavernous sinus or incomplete circumferential tumor resection. Of these 19 patients, 6 were in remission in the immediate postoperative period despite of intraoperative findings. So far, adjuvant sellar/parasellar radiation (administered to 10/19) has resulted in remission in eight patients. One has undergone bilateral adrenalectomy. The median length of follow-up for the entire cohort was 32 months. Postoperative complications include delayed central sinus thrombosis and transient cranial nerve 6th palsy in one patient each.

Conclusion: Our study suggests that preoperative MRI underestimates cavernous sinus invasion in CD. The indications for cavernous sinus exploration include adenoma adherence to or invasion of the medial wall of the cavernous sinus. We find that the medial wall of the cavernous sinus can be removed safely and effectively leading to durable remission from CD in many instances. Additionally, we illustrate the necessity for adjuvant radiation therapy when it is evident intraoperatively that gross total resection cannot be achieved (even if hormone values suggest endocrinologic remission).