Second-Day Morning Cortisol Levels after Transsphenoidal Surgery Are Accurate Predictors of Secondary Adrenal Insufficiency with Diagnostic Cut-Offs Similar to Those in Non-Stressed Conditions

Introduction: Multiple studies tried to identify cortisol cut-offs after pituitary surgery that could accurately assess hypothalamic-pituitary-adrenal (HPA) axis function; however, there is no consensus nowadays. This study aimed to evaluate the accuracy of morning cortisol after transsphenoidal surgery in predicting long-term secondary adrenal insufficiency. Methods: In our tertiary center, we prospectively determined first- and second-day cortisol after transsphenoidal surgery in 92 patients without preoperative adrenal -insufficiency and not treated with glucocorticoids perioperatively. Definitive diagnosis of secondary adrenal insufficiency was obtained with re-evaluation 3 months after trans-sphenoidal surgery and clinical follow-up of at least 1 year. Results: Ten patients (10.8%) developed long-term postoperative secondary adrenal insufficiency. The ROC curves demonstrated that first-day cortisol had a moderate diagnostic accuracy, while a second-day cortisol ≤9.3 μg/dL (257 nmol/L) showed the best performance in predicting adrenal insufficiency (sensitivity [Se] 88.9%, specificity [Sp] 86.9%, AUC 0.921). Moreover, a second-day cortisol ≤3.2 μg/dL (89 nmol/L) was able to diagnose adrenal insufficiency in 100% of cases (Se 22.2%, Sp 100%) and >14 μg/dL (386 nmol/L) was able to exclude ACTH deficiency (Se 100%, Sp 57.4%). Conclusions: Adrenal function can be carefully studied on the second day after pituitary surgery, using cut-off values that international guidelines suggested for non-stressed conditions. In fact, second-day cortisol levels ≤3.2 μg/dL (89 nmol/L) and >14 μg/dL (386 nmol/L) are diagnostic of secondary adrenal insufficiency and normal function, respectively. We also suggest performing a definitive re-evaluation with an HPA axis stimulation test when second-day cortisol values are between 3.3 and 14 μg/dL (90-386 nmol/L).