Recovery of the hypothalamo-pituitary-adrenal axis following trans-sphenoidal adenomectomy for non-ACTH secreting macroadenomas.

CONTEXT: Secondary adrenal insufficiency is a potential complication of trans-sphenoidal adenomectomy (TSA). Most centers test recovery of the hypothalamo-pituitary-adrenal (HPA) axis six weeks after TSA but there are no data predicting likelihood of recovery, or the frequency of later recovery of HPA function and hence need for re-testing. OBJECTIVE: To assess timing and predictors of hypothalamo-pituitary adrenal (HPA) axis recovery after TSA. DESIGN: Single-centre, retrospective analysis of consecutive pituitary surgeries performed on individuals between February 2015 and September 2018. PATIENTS: One hundred and nine patients were identified who had Short Synacthen Test (SST) data before and at sequential time points after TSA. MAIN OUTCOME MEASURES: Recovery of HPA axis function at 6-weeks, 3-months, 6-months and 9 to12-months post-TSA. RESULTS: 21.1% of the cohort failed the pre-op SST. Among these patients with pre-operative adrenal insufficiency, 34.8% recovered 6-weeks post-TSA. Among the 65.2% (n=15) remaining, 13.3% and 20% recovered at 3 months and 9 to 12 months respectively. Of the 29% of patients who failed the 6-week SST: 16%,12%,6% subsequently recovered at 3, 6 and 9-12 months respectively. Pre-op SST 30-minute cortisol, post-op day 8 cortisol and 6-week post-op SST baseline cortisol respectively above or below 430nmol/L(15.5μg/dL, AUC ROC=0.86), 160nmol/L(5.8μg/dL, AUC ROC=0.75) and 180nmol/L(6.5μg/dL, AUC ROC=0.88) were identified as cut-offs for predicting 6 weeks HPA recovery respectively. No patients with all three cut-offs below the threshold recovered within 12 months post-TSA whereas 92% with all cut-offs above the threshold recovered HPA function within 6 weeks (OR 12.200,95%CI 5.268-28.255). CONCLUSIONS: HPA axis recovery can occur as late as 9-12 months following TSA demonstrating the need for periodic reassessment of patients who initially 'fail' SST post-TSA. Cortisol levels from the SST before and after surgery can be used to guide which patients are likely to recover function and therefore avoid unnecessary lifelong glucocorticoid replacement.