Effectiveness of Bilateral Inferior Petrosal Sinuses Sampling in Tumor Lateralization: Intraoperative Findings and Postoperative Results

Introduction: The diagnosis and treatment of Cushing´s Disease is a demanding endeavor. A multi-disciplinary approach using state-of-the-art imaging and laboratory tests is mandatory. Alas, numerous patients with central hypercortisolism present without any identifiable lesions in MRI. We believe IPSS is an invaluable tool in preoperative tumor lateralization with a direct impact in surgical outcomes and disease remission rates.

Methods: Fifty-two consecutive patients with Cushing´s Disease and no abnormal findings in contrast-enhanced MRI were enrolled between 2009 and 2015. Selective bilateral Inferior Petrosal Sinus catheterization was performed via bilateral femoral artery puncture. Samples were taken from both IPS and a peripheral vein before and three, five and ten minutes after stimulation with Corticotropin-Releasing Hormone (CRH) and were sent for Adrenocorticotropic Hormone (ACTH) level measurement. Significant lateralization was considered as a 3-fold difference between sides. Peripheral measurements were used to ensure all patients had Cushing´s Disease. Patients were deemed to have no lateralization when both sides had a two-to-3-fold increase in comparison with peripheral measurement but no significant differences were found between sides. All patients underwent Endoscopic Transsphenoidal resection. Demographic, biochemical and imaging data were prospectively collected and reviewed six and twelve months after surgery.

Results: Twenty-five (48%) and twenty (38.4%) patients had right and left lateralization, respectively. The remaining seven patients (13.6%) had bilateral ACTH elevation after CRH-induced stimulation without significant difference between sides and were deemed to have no lateralization. During surgical exploration twenty-two patients (42.3%) were found to have a macroscopic lesion that was not evident in preoperative, independently-evaluated MRI studies and was thus resected. All patients with bilateral elevation were found to have a midline lesion while the remaining fifteen patients had the lesion on the side predicted by IPSS. Thirty patients (57.7%) had no macroscopic lesion during careful endoscopic dissection by an experienced skull-base neurosurgeon. Hemi-hypophysectomy was performed based on IPSS findings on all but two of the patients who had only authorized resection if a lesion was found. Of the patients with lesion resection nineteen of twenty two (86%) had biochemical remission by six and twelve months. Twenty-two patients who underwent hemi-hypophysectomy had biochemical remission by six months (73%). At the 12-month evaluation, two patients had disease recurrence with twenty patients still disease-free (66.6%).

Conclusions: We found a significant amount of patients with normal MRI have a macroscopic lesion that is found when careful and thorough dissection is undertaken by an expert neurosurgeon. When no lesion is evident either by imaging studies or direct visualization, we recommend performing a hemi-hypophysectomy based on the IPSS findings with a significant remission rate (73 and 66% by 6 and 12 months, respectively) in patients that would otherwise remain with a challenging, potentially lethal disorder. Long-term evaluation is ongoing. Two and five-year follow-up results will be eventually published.