The relationship between early post‐operative ACTH / cortisol following pituitary surgery and long‐term glucocorticoid requirement – Do ultradian rhythms matter?

Objective To determine whether early (4‐8h) post‐operative ACTH after trans‐sphenoidal surgery (TSS) predicts long‐term hypothalamic–pituitary–adrenal (HPA) axis function and to investigate early morning day 1 ACTH/cortisol variability using rapid sampling. Design Prospective observational study. Methods Participants undergoing TSS were included; those treated with glucocorticoids pre‐operatively received 100 mg intravenous hydrocortisone on anaesthetic induction. ACTH and cortisol were measured post‐operatively at + 4h and + 8h after induction and on day 1 every 10 minutes between 0700h and 0900h. Primary outcome: glucocorticoid requirement at 6 months. Results Nineteen participants (10F, 9M): 6/19 (32%) were treated with replacement glucocorticoids pre‐operatively; 4 had ceased by 6 weeks post‐operatively. One patient developed new hypopituitarism post‐operatively meaning 3/19 (16%) required glucocorticoids at 6 months. Post‐operative + 4h ACTH < 14.3 pmol/L (65 ng/L) predicted secondary adrenal insufficiency (SAI) (sensitivity 100%, specificity 75%), whilst no participant with a post‐operative + 4h ACTH ≥ 14.3 pmol/L (65 ng/L) required glucocorticoids at 6 months. Day 1 ACTH and cortisol showed a significant circadian fall between 0700h‐0900h; ACTH 4.2 pmol/L (IQR 2.9‐5.9) to 3.7 pmol/L (IQR 2.9‐5.1) P  = .006 and cortisol 549 nmol/L (IQR 337‐618) to 439 nmol/L (IQR 315‐606) P  < .001, with clinically insignificant ultradian secretory pulses. Conclusions No participant with a post‐operative + 4h ACTH ≥ 14.3 pmol/L (65 ng/L) required glucocorticoids at 6 months; however, given only 3/19 participants had the primary outcome of interest, this must be confirmed in a larger cohort. The timing of a day 1 morning cortisol between 0700h and 0900h influences the accuracy of a single cut‐off to diagnose SAI after pituitary surgery.