Diagnostic Threshold for Postoperative Secondary Adrenal Insufficiency After Transsphenoidal Resection of Pituitary Adenomas

Transsphenoidal surgery (TSS) is the first line treatment for pituitary adenomas. A well-known complication of TSS is secondary adrenal insufficiency with a reported risk of 4-9% after TSS. Currently, glucocorticoid replacement is recommended if postoperative AM cortisol is < 3 ug/dL. Postoperative adrenal insufficiency is ruled out if AM cortisol is > 15 ug/dL. However, further evaluation of the adrenal axis with ACTH stimulation test is recommended for intermediate cortisol levels 3-15 ug/dL. Other studies have proposed postoperative cortisol threshold of < 4-14 ug/dL for glucocorticoid replacement. Retrospective analysis of all patients undergoing TSS at a tertiary center from January 2013 through April 2016 was performed. ACTH producing adenomas (Cushing’s disease) were excluded. Of the 97 patients included, 17.5% (n=17) had secondary adrenal insufficiency requiring glucocorticoid replacement at 1 year post operatively. Mean age at presentation was 56 ± 16 years and 52% were female. Mean adenoma size was 25.3 ± 11.3 mm. Factors associated with adrenal insufficiency at 1 year post operatively were preoperative secondary adrenal insufficiency (AM cortisol 4.5 ± 1.9 vs 11.0 ± 1.0 µg/dL; p = 0.03), and preoperative adenoma contact with optic chiasm (15.7% vs 2.1%; p = 0.01). Day 1-7 postoperative cortisol was lower in the group with adrenal insufficiency at 1 year (5.6 µg/dL (IQR 1.9-11.5) vs 19.8 µg/dL (IQR 12.75-43.2); p=0.02). Age, gender, adenoma size, and cavernous sinus involvement were not associated with adrenal insufficiency at 1 year. A day 1-7 postoperative cortisol concentration of ≥8.0 µg/dL had a sensitivity of 75% and specificity of 92% in predicting adrenal insufficiency at 1 year. In patients with secondary adrenal insufficiency at 1 year (n=17), there was a higher frequency of concomitant loss of other pituitary hormone function at 1 year: secondary hypothyroidism 82% (n=14), secondary hypogonadism 70.6% (n=12) and diabetes insipidus 17.7% (n=3). A lower postoperative cortisol threshold of 8 µg/dL can be adopted for glucocorticoid replacement on discharge after TSS.