Management of Cushing’s disease (CD) has traditionally relied on a strict binary paradigm based on MRI findings (MRI-positive vs. MRI-negative cases). In a recent study published in Brain and Spine, the Neurosurgery team at Lariboisière Hospital proposes moving beyond this dichotomy by conceptualizing CD as a radiological, clinical, and functional spectrum guided by a stepwise surgical strategy.

Moving Beyond the MRI-Positive / MRI-Negative Dichotomy

Corticotroph pituitary tumors are microadenomas in up to 90% of cases. Despite advances in high-resolution 3T MRI, no clear lesion is identified in 23% to 50% of patients during initial workup.

While useful, the classic binary classification fails to reflect the true heterogeneity of corticotroph tumors and intraoperative decision-making. The conceptual framework established by the Lariboisière surgical team redefines CD as a continuous spectrum:

MRI-positive lesions with invasive features: Micro- or macroadenomas with basal dural or cavernous sinus invasion.
MRI-equivocal findings: Consistent focal or bifocal T1/T2 signal heterogeneities requiring targeted surgical exploration.
MRI-negative disease: Absence of a radiological target despite repeated high-resolution MRIs, requiring systematic intraoperative exploration.

A Stepwise Surgical Strategy

Drawing from a prospective database of over 980 patients operated for Cushing’s disease between 2006 and 2025, this study details the decision-making algorithm refined by the expert team using a mononostril endoscopic transsphenoidal approach:

1. Workup & Repeat Imaging

Preoperative cortisol control (e.g., with osilodrostat) improves patient condition and provides time for repeated high-resolution MRI. Over 70% of initially negative MRIs eventually reveal a target on repeat scans. Molecular imaging (FET-PET) and IPSS further guide lateralization.

2. Targeted Resection & Dural Extension

For well-circumscribed tumors, selective adenomectomy is performed. When basal dural or cavernous sinus medial wall invasion is identified, extended dural resection is conducted to maximize endocrine remission rates.

3. Exploration of MRI-Negative Cases

If imaging remains strictly normal, systematic bilateral gland exploration is performed. Resection is tailored based on intraoperative tissue findings (enlarged adenomectomy or partial hypophysectomy).

Outcomes and Clinical Impact

Key results from the illustrative series across the CD spectrum include:

Early Endocrine Remission: Achieved in 6 out of 7 patients, with the remaining patient achieving postoperative eucortisolism.
Surgical Safety: Transient diabetes insipidus was the only reported complication, with no permanent hypopituitarism or neurovascular injury.

This dynamic framework demonstrates that an individualized, stepwise surgical strategy delivers high cure rates while preserving pituitary function, even in complex or MRI-negative cases.

Publication Reference

Ferlendis L, Chu HT, Passeri T, Villa C, Leclercq D, Barat M, Fava A, Beccaria K, Assié G, Froelich S, Baussart B. Beyond the MRI-positive/MRI-negative dichotomy: A stepwise surgical strategy for Cushing’s disease. Brain Spine. 2026 Sep 5;6:106668. doi:10.1016/j.bas.2026.106668. Read Full Article (Open Access) ➤