MRI-negative Cushing’s Disease: Management Strategy and Outcomes in 15 Cases Utilizing a Pure Endoscopic Endonasal Approach

Abstract

Background Cushing’s disease (CD) is among the most common etiologies of hypercortisolism. Magnetic resonance imaging (MRI) is often utilized in the diagnosis of CD, however, up to 64% of adrenocorticotropic hormone (ACTH)-producing pituitary microadenomas are undetectable on MRI. We report 15 cases of MRI negative CD who underwent surgical resection utilizing a purely endoscopic endonasal approach. Methods Endoscopic endonasal transsphenoidal surgery (EETS) was performed on 134 CD cases by a single surgeon. Fifteen cases met inclusion criteria: no conclusive MRI studies and no previous surgical treatment. Data collected included signs/symptoms, pre- and post-operative hormone levels, and complications resulting from surgical or medical management. Data regarding tumor diameter, location, and tumor residue/recurrence was obtained from both pre- and post-operative MRI. Immunohistochemistry was performed to assess for tumor hormone secretion. Results Aside from a statistically significant difference (P = 0.001) in histopathological results between patients with negative and positive MRI, there were no statistically significant difference between these two groups in any other demographic or clinical data point. Inferior petrosal sinus sampling (IPSS) with desmopressin (DDAVP®) administration was performed on the 15 patients with inconclusive MRIs to identify the origin of ACTH hypersecretion via a central/peripheral (C/P) ratio. IPSS in seven, five and three patients showed right, left, and central side lateralization, respectively. With a mean follow-up of 5.5 years, among MRI-negative patients, 14 (93%) and 12 patients (80%) achieved early and long-term remission, respectively. In the MRI-positive cohort, over a mean follow-up of 4.8 years, 113 patients (94.9%) and 102 patients (85.7%) achieved initial and long-term remission, respectively. Conclusions Surgical management of MRI-negative/inconclusive Cushing’s disease is challenging scenario requiring a multidisciplinary approach. An experienced neurosurgeon, in collaboration with a dedicated endocrinologist, should identify the most likely location of the adenoma utilizing IPSS findings, followed by careful surgical exploration of the pituitary to identify the adenoma.

Medium and Long-Term Data from a Series of 96 Endoscopic Transsphenoidal Surgeries for Cushing Disease

“…In the series presented by Sharifi et al [ 35 ] and some other series [ 8 , 12 , 32 , 36 ], no significant difference was observed between the remission rates of CD cases with and without a conclusive MRI.This finding is controversial since other studies showed decreased remission rates with preoperative inconclusive MRIs [ 13 , 40 ]. Similar to the results reported by Sharifi et al [ 35 ], we did not find a statistically significant difference between the remission rates of tumors <6 mm and those between 6–20 mm. However, a significant difference was observed between tumors <6 mm and those ≥20 mm.…”

“…In our series, when the tumors were stratified further by the tumor size, the medium-term remission rate further decreased to 36% for tumors ≥20 mm in size, although the remission rates for other groups <20 mm were all above 75% ( p =0.003). Sharifi et al [ 35 ] classified pituitary MRI scans in CD showing a tumor size <6 mm as “inconclusive” because incidentalomas are frequent among tumors in this size range, and this size is not indicative of CD. Previously published series reported that the rate of inconclusive MRI scans in CD was 36–64%, and the remission rates varied between 50% and 71% for those with an inconclusive MRI scan [ 10 , 24 , 27 , 32 , 33 ].…”

Endoscopic endonasal approach for MRI–Negative Cushing’s microadenoma

“…The surgical approach differs from conventional resection of pituitary adenomas visible on MRI, as emphasis is placed on the exploration of the pituitary gland and the cavernous sinus while preserving as much of the normal gland as possible. 1 …”

Endoscopic Endonasal Transsphenoidal Resection for MRI-Negative Cushing Disease With 2 Separate Functioning Pituitary Adenomas Neuroendocrine Tumors: 2-Dimensional Operative Video

“…1 However, the surgical approach to MRI-negative CD presents significant challenges, given that many CDs exhibit no visible tumor despite the advancements in pituitary imaging. 2-6 This leads to the decision to undertake surgery in MRI-negative CD remaining a contentious issue. Furthermore, the rare manifestation of double pituitary tumors is predominantly associated with adrenocorticotropic hormone (ACTH)–secreting or growth hormone–secreting tumors.…”