Delayed Remission after Transsphenoidal Surgery in Patients with Cushing's Disease

Elena Valassi, Beverly M. K. Biller, Brooke Swearingen, Francesca Pecori Giraldi, Marco Losa, Pietro Mortini, Douglas Hayden, Francesco Cavagnini,  and Anne Klibanski*

Neuroendocrine Unit (E.V., B.M.K.B., A.K.) and Department of Neurosurgery (B.S.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Chair of Endocrinology (E.V., F.P.G., F.C.), Universita' di Milano, Ospedale San Luca, Istituto Auxologico Italiano, Istituto di Ricovero e Cura a Carattere Scientifico, 20149 Milan, Italy; Department of Neurosurgery (M.L., P.M.), Universita' Vita-Salute, Istituto Scientifico San Raffaele, 20132 Milan, Italy; and Biostatistics Center (D.H.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114

* To whom correspondence should be addressed. E-mail: aklibanski@partners.org.

Background: Transsphenoidal surgery (TSS) is the treatment of choice for Cushing's disease (CD). Postoperative hypercortisolemia mandates further therapy.

Objective: The aim of the study was to characterize patients without immediate postoperative remission who have a delayed decrease to normal or low cortisol levels without further therapy.

Design and Setting: A retrospective case series was conducted at three tertiary care centers.

Patients and Intervention: We reviewed the records of 620 patients (512 females, 108 males; mean age, 38 ± 13 yr) who underwent transsphenoidal pituitary surgery for CD between 1982 and 2007.

Results: Outcomes were classified into the following three groups based upon the postoperative pattern of cortisol testing: group IC (immediate control) included 437 of the 620 patients (70.5%) with hypocortisolism and/or cortisol normalization throughout the postoperative follow-up; group NC (no control) included 148 of 620 patients (23.9%) with persistent hypercortisolism; and group DC (delayed control) included 35 of 620 patients (5.6%) who had early elevated or normal UFC levels and developed a delayed and persistent cortisol decrease after an average of 38 ± 50 postoperative days. The total rate of recurrence was 13% at a median follow-up time of 66 months after TSS; the cumulative rate of recurrence at 4.5 yr was significantly higher in group DC vs. group IC (43 vs. 14%; P = 0.02).

Conclusions: Hormonal assessment in the immediate postoperative period after TSS for CD may be misleading because delayed remission can occur in a subset of patients. Expectant management and retesting may spare some patients from unnecessary further treatment. Optimal timing to determine the need for further therapy after TSS remains to be determined.

From http://jcem.endojournals.org/cgi/content/abstract/jc.2009-1672v1