Impact of Venous Drainage on Tumor Lateralization in Inferior Petrosal Sinus Sampling: Reappraisal With Literature Review.

Introduction Venous drainage patterns may compromise the ability of inferior petrosal sinus sampling (IPSS) to correctly lateralize corticotroph tumors in Cushing's disease. We aimed to reappraise this effect in patients proceeding to transsphenoidal surgery (TSS) and to contextualize our findings with a brief review of the literature. Methods We retrospectively reviewed the records of 37 consecutive patients who underwent IPSS at our institution between April 2018 and March 2025. Of these, 28 subsequently underwent TSS based on IPSS findings and other clinical data. Corticotroph pituitary neuroendocrine tumors were histologically confirmed in 25 patients. We compared IPSS-indicated lateralization with the intraoperatively determined and histopathologically confirmed tumor side, and we systematically evaluated the influence of venous drainage patterns on false lateralization. Results Of the 25 histologically confirmed cases, IPSS lateralization agreed with the actual tumor side in 22 patients (88%), including eight with venous drainage from the tumor side toward the contralateral side. In contrast, three patients (12%) showed false lateralization, in which IPSS indicated the opposite side of the actual tumor. All three false-lateralized cases exhibited dominant contralateral venous drainage, and prolactin-adjusted values did not alter the interpretation. Overall, among 11 patients with dominant contralateral drainage, IPSS misidentified the tumor side in three (27%). Discussion IPSS demonstrated high lateralization accuracy in our cohort; however, dominant venous drainage from the tumor to the contralateral side may result in false lateralization. Careful assessment of venous outflow patterns is essential, particularly when IPSS findings contradict MRI-based lateralization, to support appropriate surgical decision-making.