Postoperative Day 1 and 2 Morning Cortisol Levels: Analysis of Predictive Utility for Endocrine Sequelae in Pituitary Surgery

Introduction: Adrenal insufficiency (AI) is an uncommon sequela following resection of pituitary adenomas (PAs). This study evaluates the predictive utility of postoperative day (POD) 1 and 2 morning (AM) cortisol for endocrinological outcomes following PA resection.

Methods: Patients who underwent resection of PAs between June 2012–August 2023 were included if POD1 or POD2 AM serum cortisol levels and minimum one-year endocrine follow-up were available. Patients with pre-existing Cushing’s syndrome or steroid administration preoperatively, intraoperatively, or on POD1 or POD2 mornings were excluded. Logistic regression and ROC analysis were conducted to assess the predictive utility of POD1 or POD2 AM cortisol for various endocrine outcomes, with optimal cut-off values determined using Youden's index.

Results: Of 230 patients (60.0% female, mean age=51.4 years), 8.3% developed new transient or permanent AI postoperatively. At most recent follow-up, 2.2% had permanent AI, 17.0% had new hypogonadotropic hypogonadism (HGHG), and 13.0% had new hypothyroidism. Logistic regression revealed that each 1 µg/dL increase in POD1 AM cortisol was associated with reduced odds of overall AI by 7.3% (OR=0.927, 95%CI:0.884–0.972, p=0.002), permanent AI by 9.5% (OR=0.905, 95%CI:0.824–0.994, p=0.039), and HGHG by 5.7% (OR=0.943, 95%CI:0.915–0.972, p< 0.001). In those who received additional testing, often due to equivocal POD1 results, each 1 µg/dL increase in POD2 AM cortisol was associated with reduced odds of overall AI by 70.4% (OR=0.296, 95%CI:0.178–0.492, p< 0.001), permanent AI by 63.4% (OR=0.366, 95%CI:0.214–0.626, p< 0.001), HGHG by 18.0% (OR=0.820, 95%CI:0.748–0.899, p< 0.001), and hypothyroidism by 24.9% (OR=0.751, 95%CI:0.675–0.836, p< 0.001). In this context, POD2 AM cortisol significantly predicts overall AI (AUC=0.990, p< 0.001) and permanent AI (AUC=0.987, p=0.005) with a cut-off of 4.95 µg/dL (sensitivity: 100%, specificity: 96.1%) and also demonstrated significant predictive ability for HGHG and hypothyroidism.

Conclusion : POD2 AM cortisol is a strong predictor of new AI and other long-term endocrine disorders when used as additional confirmatory testing in the context of POD1 results. Collection of POD2 AM cortisol may improve postoperative risk stratification and guide timely intervention in this patient subset following PA resection.