Dynamics of serum cortisol levels after transsphenoidal surgery in a cohort of patients with Cushing's disease

Transsphenoidal pituitary surgery is the treatment of choice for Cushing's disease (CD). Despite the widespread acceptance of this procedure, there is no agreement regarding the definition of successful treatment. We prospectively studied postoperative serum cortisol dynamics in 41 patients with CD ( including a total of 45 surgeries). The mean postoperative follow-up period was 4.8 yr. Remission was defined as clinical and laboratory signs of adrenal insufficiency, glucocorticoid dependence, and serum cortisol suppression on overnight oral 1-mg dexamethasone suppression test. Serum cortisol was measured preoperatively and postoperatively at 6, 12, and 24 h ( 28 surgeries) and at 10 - 12 d ( 45 surgeries). No statistical difference was detected in mean preoperative and 6-h postoperative cortisol levels between surgically induced remission patients [22.1 +/- 7.73 mug/dl (610 +/- 213.3 nmol/liter) and 25.2 +/- 19 mug/dl (695.2 +/- 524.4 nmol/liter)] and surgical failure patients [23.6 +/- 6.95 mug/dl (651.4 +/- 161.8 nmol/liter) and 37.5 +/- 18.1 mug/dl (1035 +/- 499.6 nmol/liter); P = 0.50 and P = 0.17]. At 12 and 24 h after surgery, the difference was significant (P = 0.009 and P < 0.0001). Mean cortisol levels were 12.44 +/- 13.3 mu g/dl (343.3 +/- 367.1 nmol/liter) and 4.72 +/- 6.72 mu g/dl (130.3 +/- 185.5 nmol/liter) in the remission group and 26.3 +/- 7.06 mu g/dl (725.9 +/- 194.8 nmol/liter) and 23.5 +/- 6.86 mu g/dl (648.6 +/- 189.3 nmol/liter) in the failure group ( P = 0.009; P< 0.0001). At 10 - 12 d after the procedure, the difference was also significant ( P < 0.0001): cortisol levels were 2.52 +/- 3.32 mu g/dl (69.5 +/- 91.6 nmol/ liter) in the remission group and 24.9 +/- 13.3 mu g/dl (687.2 +/- 367.1 nmol/ liter) in the failure group. In conclusion, in the immediate postoperative period of transsphenoidal surgery, remission of CD is not necessarily defined by undetectable serum cortisol. During the first 10 - 12 d after surgery, cortisol nadir correctly classified the remission [ cortisol, 7.0 mu g/dl (193.2 nmol/ liter) or less] and the failure groups [ cortisol, 8.0 mu g/dl (220.8 nmol/ liter) or more]. Glucocorticoid should be administered only after laboratory and/or clinical evidence of adrenal insufficiency.