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
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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.