Second day morning cortisol levels after transsphenoidal surgery are accurate predictors of secondary adrenal insufficiency with diagnostic cut-offs similar to non-stressed conditions.

BACKGROUND: Multiple studies tried to identify cortisol cut-offs after pituitary surgery able to assess accurately hypothalamic-pituitary-adrenal 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 perioperative. Definitive diagnosis of secondary adrenal insufficiency was obtained with re-evaluation three months after transsphenoidal surgery and clinical follow-up of at least one year.

RESULTS: 10 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 (Se 88.9%, 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 in 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).