MRI-Negative Cushing's Disease: A Systematic Review and Meta-Analysis

Objective: In this systematic review and meta-analysis, we review the literature regarding pituitary-dependent Cushing's disease (CD) patients with negative or inconclusive MRI. This review will analyze demographics, information about the type of operation, and surgical outcomes such as remission, persistence, and recurrence. Based on this information, we will suggest which therapeutic approach is more efficient in managing patients with pituitary-dependent CD.

Methods: A quantitative systematic review was performed. Article selection was performed by searching MEDLINE (using PubMed), EMBASE, and Cochrane electronic bibliographic databases. The keywords used include “Magnetic resonance imaging’ OR “MRI” AND “Negative” OR “Equivocal” AND “ACTH secreting pituitary adenoma” OR “Cushing disease” AND “hypophysectomy” OR “adenectomy” OR “Endoscopy” OR “Endonasal transsphenoidal” OR “Endoscopic endonasal transsphenoidal” OR “Microscopic endonasal transsphenoidal” OR “radiation” OR “radiotherapy” OR “radiosurgery” OR “Medical Treatment.” The search strategy was not limited by study design.

Results: Twenty-eight articles described surgical management of inconclusive MRI or MRI-negative CD. Of these studies, a total of 858 patients underwent surgery for their Cushing adenoma. 73.7% of patients were female, and the mean age of MRI-negative CD adult patients was 41.6 years. Different types of surgery, including endoscopic endonasal transsphenoidal surgery (EETS) (190 cases) and microscopic endonasal transsphenoidal surgery (METS) (488 cases), were performed on MRI-negative CD patients. Seven studies, which included 164 patients, didn’t describe any surgery. EETS and METS are conducted to achieve selective adenomectomy (231 cases), partial adenomectomy (80 cases), total adenomectomy (13 cases), hemi-hypophysectomy (15 cases), or enlarged adenomectomy (48 cases). Based on available data on these studies, the remission rate, persistence rate, and recurrence rate after different types of surgeries on MRI-negative CD patients were 72.97, 27.03, and 12.05%, respectively. There was no statistically significant difference between EETS and METS in the subanalysis regarding recurrence rate, remission rate, and persistence rate. However, the recurrence rate in the METS group is almost three times higher than in the EETS group. Also, we proposed an approach to the management of MRI-negative Cushing's disease patients with positive IPSS.

Conclusion: Surgery has a great prognosis in MRI-negative CD patients in terms of remission, and EETS has a lower rate of disease recurrence than METS; therefore, EETS is the potential recommended treatment technique in these patients ([Figs. 1]–[4]).

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Publication History

Article published online:
15 February 2022