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

Neuroendocrinology. 2021;111(7):639-649. doi: 10.1159/000509092. Epub 2020 Jun 3.

Abstract

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).

Keywords: Adrenal insufficiency; Neurosurgery; Pituitary surgery; Pituitary tumors; Pituitary-adrenal system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Insufficiency / blood*
  • Adrenal Insufficiency / diagnosis*
  • Aged
  • Female
  • Humans
  • Hydrocortisone / blood*
  • Male
  • Middle Aged
  • Natural Orifice Endoscopic Surgery
  • Neurosurgical Procedures
  • Pituitary Diseases / surgery*
  • Prospective Studies
  • Sphenoid Sinus
  • Time Factors

Substances

  • Hydrocortisone