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Dynamics of Serum Cortisol Levels after Transsphenoidal Surgery in a Cohort of Patients with Cushing’s Disease

Division of Endocrinology (G.A.F.S.R., M.J., J.L.G., M.A.C.), Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil CEP 90035-003; Hospital São José (N.P.F.), Irmandade da Santa Casa de Misericórdia, Porto Alegre, Brazil CEP 90020-090; and Graduate Program in Endocrinology (G.A.F.S.R., M.J., J.L.G., M.A.C.), School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil CEP 90022-003

Address all correspondence and requests for reprints to: Professor Dr. Mauro A. Czepielewski, Serviço de Endocrinologia, Hospital de Clínicas de Porto Alegre, Avenue Ramiro Barcelos, 2350/Prédio 12, 4 andar; CEP 90035-003, Porto Alegre, Brazil. E-mail: maurocze{at}terra.com.br.

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 µg/dl (610 ± 213.3 nmol/liter) and 25.2 ± 19 µg/dl (695.2 ± 524.4 nmol/liter)] and surgical failure patients [23.6 ± 6.95 µg/dl (651.4 ± 161.8 nmol/liter) and 37.5 ± 18.1 µg/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 µg/dl (343.3 ± 367.1 nmol/liter) and 4.72 ± 6.72 µg/dl (130.3 ± 185.5 nmol/liter) in the remission group and 26.3 ± 7.06 µg/dl (725.9 ± 194.8 nmol/liter) and 23.5 ± 6.86 µg/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 µg/dl (69.5 ± 91.6 nmol/liter) in the remission group and 24.9 ± 13.3 µg/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 µg/dl (193.2 nmol/liter) or less] and the failure groups [cortisol, 8.0 µg/dl (220.8 nmol/liter) or more]. Glucocorticoid should be administered only after laboratory and/or clinical evidence of adrenal insufficiency.

This work was supported in part by a grant from the Hospital de Clínicas de Porto Alegre.

Abbreviations: CD, Cushing’s disease; DDAVP, 1-disamino-ß-D- arginine vasopressin; TSS, transsphenoidal pituitary surgery; UFC, urinary free cortisol.

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