Hypothalamicpituitaryadrenal (HPA) axis function after trans-sphenoidal pituitary surgery is commonly assessed using post-operative morning cortisol. We performed a prospective study to determine the sensitivity and specificity of cortisol and ACTH measured within the first 24 h, in predicting glucocorticoid requirement at 6 months both in patients with pre-operative secondary adrenal insufficiency (SAI) and with normal pituitary function. Exclusion criteria included exogenous supraphysiological glucocorticoids, pregnancy and Cushings disease. ACTH and cortisol were measured at +4 h and +8 h after induction of anaesthesia on Day 0 and every 10 min between 0700 h and 0900 h on Day 1.
Results: Five of 19 participants had pre-operative SAI, of which 3 recovered post-operatively. One participant with normal HPA function pre-operatively developed symptomatic diabetes insipidus and SAI after Day 1. At 6 months, 3 participants required glucocorticoids (SAI) and 16 did not (normal HPA axis). ACTH on Day 0 at +4 h ≥65 ng/l predicted a normal HPA axis at 6 months (AUC:0.844, P=0.004, sensitivity:100%, specificity:75%), but not +8 h levels (P=0.697). Serial cortisol measured between 0700 h0900 h showed median difference between peak and trough concentrations of 172 nmol/l (IQR 121198). Day 1 ultradian cortisol peaks occurred at 0710 h and 0840 h and cortisol levels of ≥445 nmol/l (AUC:0.844, P=0.04, sensitivity:100%, specificity:69%) and ≥307 nmol/l (AUC:0.9, P<0.001, sensitivity:100%, specificity:80%) respectively, predicted normal HPA axis at 6 months. Combining Day 0 +4 h ACTH and Day 1 cortisol levels referenced to these peaks increased the specificity to 87.5% and 100%, respectively, whilst maintaining 100% sensitivity. Three Day 1 morning cortisol levels taken 30 min apart between 0700 and 0900 h, increased the probability of sampling an ultradian peak within 10 min to 100%.
Conclusion: Immediate post-operative +4 h ACTH and three Day 1 morning cortisol samples 30 min apart between 0700 and 0900 h predict a normal HPA axis at 6 months. Patients with new onset symptomatic SAI or pituitary dysfunction require further testing.