Basis of persistent and recurrent Cushing disease: an analysis of findings at repeated pituitary surgery

OBJECT: The goal of this study was to establish the clinical importance of occult dural invasion--invasion of the dura mater or cavernous sinus that is not evident on imaging studies and is not obvious to the surgeon--as the basis of recurrent or persistent tumor and endocrinopathy. METHODS: The authors retrospectively reviewed the case files of patients who underwent repeated transsphenoidal surgery for resection of an adrenocorticotropic hormone (ACTH)-producing pituitary adenoma. Patient selection required the availability of operative and pathology reports from the initial and repeated transsphenoidal surgeries. Because no determination of the cause of persistent or recurrent disease could be made if the tumor could not be localized during the repeated surgery, a pathology report confirming the presence of tumor from the second surgery was also required. Sixty-eight patients met these criteria. In 43 patients (63%) an ACTH-producing tumor was identified at the initial surgery, in 25 patients (37%) no tumor was found, and in three patients (4%) dural invasion was noted at surgery. In 49 (72%) of the 68 patients there was initial resolution of hypercortisolism and recurrent Cushing disease (CD), whereas in 19 patients (28%) there was persistent CD after the initial surgery. At repeated surgery (44 +/- 35 months after the initial surgery) in all 43 patients in whom tumor had been identified at the initial surgery, the tumor was found at the same site or contiguous to the same site. Dural invasion was noted by the surgeon in only three patients at the original surgery, whereas dural invasion by an ACTH-producing tumor was identified during repeated surgery in 42 (62%) of the 68 patients. In addition, 39 (93%) of the 42 invasive adenomas were located laterally and involved the cavernous sinus. Adenomatous invasion of the dura mater was found in 31 (54%) of the 57 microadenomas and in all 11 macroadenomas at repeated surgery. The presence of tumor was not detected in 28 of the 59 patients studied with magnetic resonance (MR) imaging and in none of these 59 patients was dural invasion evident on MR images. CONCLUSIONS: Recurrent and persistent CD consistently results from residual tumor. At repeated surgery the residual tumor can be found at or immediately contiguous to the site at which the tumor was found originally. Unappreciated dural invasion with growth of residual tumor within the cavernous sinus dura, which frequently occurs without residual tumor or dural invasion being evident on MR images or to the surgeon during surgery, is the basis of surgical failure in many patients with CD. Occult lateral dural invasion by tumor may also underlie recurrences of other types of pituitary adenomas.