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Persistent Adrenocorticotropin Response to Desmopressin in the Early Postoperative Period Predicts Recurrence of Cushing’s Disease

Pituitary Unit of the Department of Neurosurgery, Istituto Scientifico San Raffaele, Università Vita-Salute, 20132 Milano, Italy

Address all correspondence and requests for reprints to: Marco Losa, M.D., Department of Neurosurgery, Istituto Scientifico San Raffaele, Via Olgettina 60, 20132 Milano, Italy. E-mail: losa.marco{at}hsr.it.

Context: Patients with Cushing’s disease (CD) often show an ACTH and cortisol response to desmopressin (DDAVP).

Objective: We tested whether persistence of a positive response to DDAVP after successful surgery identifies patients at risk of CD recurrence.

Design: We prospectively included all CD patients who had a positive response to DDAVP before successful surgery from 1995 through 2007.

Setting: The study was performed at a university hospital.

Patients: One hundred seventy-four patients with CD, 148 women and 26 men, mean age 36.1 ± 0.8 yr, were studied. The median follow-up after surgery was 58 months (interquartile range 22–93 months).

Intervention: DDAVP test was performed immediately before and after surgery.

Main Outcome Measure: An ACTH and cortisol increment of at least 30 and 20% above baseline, respectively, were considered as a positive response to DDAVP. The risk of CD recurrence was analyzed according to the postoperative hormonal response to DDAVP.

Results: Recurrence of CD occurred in 19 patients (10.9%). The recurrence-free survival at 5 yr was 89.8% [95% confidence interval (CI) 84.2–95.4]. Patients with a positive ACTH response had a 5-yr recurrence-free survival of 82.6% (95% CI 70.6–94.6%) as compared with 94.0% (95% CI 88.2–99.8%; P < 0.01) in patients without it. Multivariate analysis showed that persistence of a positive ACTH response to DDAVP was significantly associated with CD recurrence.

Conclusion: Positive ACTH response to DDAVP after surgery is associated with an increased risk of CD recurrence. However, the specificity and predictive value of this finding are low.