Background <p>Pituitary tumor apoplexy [PTA] and Rathke’s Cleft Cyst apoplexy (RCCA) are uncommon disorders causing hypopituitarism.</p> Objective <p>Examine the value of perioperative hormonal alterations in predicting recovery of impaired function in patients with PTA and RCCA.</p> Methods <p>Consecutive PTA (N = 97) and RCCA (N = 41) patients who had emergent surgery received dexamethasone until surgery. Perioperative HPA function and prolactin levels were frequently assessed while hydrocortisone therapy was provided to those exhibiting clinical or biochemical evidence [cortisol &lt;10 ug/dL; &lt;276 nmol/L] for insufficiency. Patients with multiple perioperative cortisol levels ≥15 ug/dL [414 nmol/L] were considered to have normal postoperative HPA function.</p> Results <p>Patients with PTA were more likely to be males, older, have more severe hormonal deficits and worse visual impairment than those with RCCA. Impaired HPA function and lower prolactin levels were more prevalent in patients with PTA than in those with RCCA. Perioperative recovery of HPA function was demonstrated by a brisk increase in ACTH followed by a rise in two ACTH-dependent adrenal steroids: cortisol and DHEA-S in 23/59 [39%] patients with PTA and in 16/20 [80%] others with RCCA. The perioperative rise in ACTH was mirrored by a decline in prolactin levels. Patients recovering function had higher [P &lt; 0.01] preoperative prolactin levels than those with persistent deficit. Follow up HPA testing confirmed perioperative assessment.</p> Conclusions <p>Perioperative measurements of ACTH and its dependent adrenal steroid levels accurately predict recovery of HPA function and support previously postulated role of increased intrasellar pressure and stalk compression in the pathogenesis of hypopituitarism in this setting.</p>