The Limited Role of Hypocortisolism in the Development of Delayed Postoperative Hyponatremia After Pituitary Surgery

PURPOSE: Delayed postoperative hyponatremia (DPH) is a common complication following pituitary surgery. Although hypocortisolism has been proposed as a contributing factor, the temporal interplay between cortisol and sodium levels remains unclear. This study aimed to elucidate the relationship between postoperative cortisol and sodium dynamics, identify independent predictors of DPH and assess potential protective factors. METHODS: We retrospectively analyzed 261 patients who underwent fully endoscopic surgery for clinically non-functioning pituitary neuroendocrine tumors (Pit-NETs, also known as pituitary adenomas) between 2021 and 2024. Serial measurements of serum sodium and morning cortisol were collected from the immediate postoperative period through 3-month follow-up. Comparative analyses between patients with and without DPH were performed to characterize hormonal and electrolyte trends. The frequency of hypocortisolism during hyponatremic episodes was compared, and multivariable logistic regression identified independent predictors. The potential protective role of preoperative steroid replacement was also evaluated. RESULTS: DPH occurred in 54 patients (20.7%), with symptomatic cases accounting for 4.2% of the cohort. The median time to nadir sodium was 8 days with a median nadir of 129 mEq/L. The serum cortisol level between hyponatremia and non-hyponatremia group did not show significant differences. For propensity score matched comparison, median nadir cortisol levels were lower in the DPH group (6.10 vs. 7.34 µg/dL, p = 0.29), and hypocortisolism during hyponatremic episodes was more frequent (48.2% vs. 40.7%, p = 0.52), though neither difference reached statistical significance. Multivariate analysis identified age > 60 years (OR 2.09, 95% CI 1.11-3.96, p = 0.023) and postoperative pneumocephalus (OR 3.28, 95% CI 1.59-6.81, p = 0.001) as independent predictors. Preoperative cortisol replacement did not demonstrate a protective effect against DPH. CONCLUSION: Hypocortisolism does not appear to be the primary mechanism underlying DPH following pituitary surgery, as evidenced by the lack of temporal correlation. Advanced age and postoperative pneumocephalus emerge as key risk factors for DPH, supporting a multifactorial etiology. Although preoperative ACTH deficiency was linked to a higher incidence of DPH, preoperative cortisol replacement was not associated with protection.