Wednesday, June 3, 2009

A Combined Dexamethasone Desmopressin Test as an Early Marker of Postsurgical Recurrence in Cushing’s Disease


Frederic Castinetti, Monique Martinie, Isabelle Morange, Henry Dufour, Nathalie Sturm, Jean-Guy Passagia, Bernard Conte-Devolx, Olivier Chabre and Thierry Brue

Service d’Endocrinologie (F.C., I.M., B.C.-D., T.B.), Diabète et Maladies Métaboliques, et Centre de Reference des Maladies Rares d’Origine Hypophysaires DEFHY, Hôpital de la Timone, 13385 Marseille, France; Service d’Endocrinologie (M.M., O.C.), Hôpital Albert Michallon, 38043 Grenoble, France; Service de Neurochirurgie (H.D.), Hôpital de la Timone, 13385 Marseille, France; and Laboratoire de Pathologie Cellulaire (N.S.), and Service de Neurochirurgie (J.-G.P.), Hôpital Albert Michallon, 38043 Grenoble, France

Address all correspondence and requests for reprints to: Prof. T. Brue, Department of Endocrinology, Hôpital de la Timone, 264 rue St. Pierre, Cedex 5, 13385 Marseille, France. E-mail:

Context: Recurrence of Cushing’s disease (CD) after transsphenoidal surgery (TSS) occurs in about 25% of cases. Twenty percent of patients with immediate postsurgical corticotroph deficiency will present late recurrence.

Objective: The aim of the study was to evaluate a coupled dexamethasone desmopressin test (CDDT) as a predictor of recurrence of CD.

Design: We conducted a prospective bicenter study (Marseille and Grenoble, France).

Patients: We studied 38 patients treated by TSS for CD with a mean follow-up of 60 months.

Intervention(s): We evaluated 24-h urinary free cortisol, ACTH, and cortisol plasmatic levels and performed low-dose dexamethasone suppression test and CDDT 3 to 6 months after surgery and then yearly.

Main Outcome Measures: After CDDT, ACTH ratio (ACTHr) was defined as (PeakACTH – BaseACTH)/BaseACTH. Cortisol ratio (Cortisolr) was defined as (PeakCortisol – BaseCortisol)/BaseCortisol. Basal values were observed after low-dose dexamethasone suppression test. Receiver operator characteristics curve defined ACTHr and Cortisolr giving the best sensitivity and specificity associated with recurrence.

Results: Ten patients presented recurrence. ACTHr and Cortisolr were superior or equal to 0.5 in all patients with recurrence and in three of 28 patients in remission (100% sensitivity, 89% specificity). The test became positive in eight of 10 patients with recurrence 6–60 months before classical markers of hypercortisolism. Six patients with immediate postsurgical corticotroph deficiency presented recurrence. All of them presented CDDT positivity during the 3 yr after surgery, and recurrence 6 to 60 months after CDDT positivity.

Conclusions: CDDT is an early predictor of recurrence of CD and could be of particular interest in the first 3 yr after surgery, by selecting patients at high risk of recurrence despite falsely reassuring classical hormonal markers.

Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2008-2234
The Journal of Clinical Endocrinology & Metabolism Vol. 94, No. 6 1897-1903
Copyright © 2009 by The Endocrine Society