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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.