Desmopressin stimulation test before and after pituitary surgery in patients with Cushing's disease

Abstract

Objective: The desmopressin test has been proposed as a useful tool for the differential diagnosis of Cushing's disease. The aim of our study was to investigate, in a large series of patients with Cushing's disease, the incidence of a positive ACTH and cortisol response to desmopressin. Moreover, we repeated the test soon after surgery to verify its usefulness in the assessment of early and late surgical results.

Patients and methods: One hundred and seven consecutive patients with Cushing's disease, 89 female and 18 male patients, with a mean age of 37.2 +/- 1.3 years, were studied. All patients, except three, repeated the test 5-6 days after surgery. Desmopressin (10 microg) was injected i.v. and blood samples were drawn 15, 30, 45 and 60 minutes thereafter. Plasma ACTH and serum cortisol were measured in duplicate by commercially available immunoassays. A positive response to desmopressin was considered to be a plasma ACTH and serum cortisol increment of at least 30% and 20% above baseline, respectively.

Results: Mean basal plasma ACTH level was 17.3 +/- 1.7 pmol/l and rose to a peak level of 42.7 +/- 4.9 pmol/l at 15 minutes Mean basal serum cortisol level was 574 +/- 19 nmol/l and rose to a peak level of 814 +/- 28 nmol/l at 45 minutes. ACTH and cortisol incremental changes were inversely correlated with their respective basal levels. Ninety patients (84.1%) had an ACTH and 84 patients (78.5%) had a cortisol response to desmopressin. Several clinical and demographic characteristics were not significantly different among desmopressin responders and non responders, except that basal ACTH and cortisol levels were significantly higher in desmopressin non responders (27.2 +/- 8.3 pmol/l, 781 +/- 86 nmol/l) than in desmopressin responders (15.4 +/- 1.2 pmol/l, 535 +/- 14 nmol/l). Disappearance of the ACTH and cortisol response to desmopressin after surgery occurred in 50 of 87 (57%) ACTH responders and in 57 of 81 (70.4%) cortisol responders, respectively. However, concordance between the desmopressin test and surgical outcome was not complete. Indeed, 18 patients considered in remission still showed an ACTH increase after desmopressin and, on the contrary, four patients with disappearance of the ACTH response had persistence of hypercortisolism. During follow-up monitoring, three patients, who had persistence of the ACTH response to desmopressin, relapsed 24, 38 and 54 months after surgery.

Conclusions: Desmopressin administration elicits a significant rise in ACTH and cortisol levels in the majority but not all patients with Cushing's disease. There is a good, but not complete, concordance between the response to the desmopressin test and the surgical outcome. Our preliminary data show that persistence of the ACTH response to desmopressin in the early postoperative period might be associated with a higher risk of late relapse.