Usefulness of the desmopressin test in the postoperative evaluation of patients with Cushing's disease

OBJECTIVE: To evaluate the plasma ACTH and serum cortisol responses to desmopressin in patients with Cushing's disease either before or after pituitary adenomectomy during long-term follow-up, and to compare the results with those obtained after corticotrophin-releasing hormone (CRH) testing. DESIGN: Plasma ACTH and serum cortisol concentrations were evaluated after the administration of desmopressin (10 microg i.v.) or CRH (1 microg/kg i. v.) in 34 patients with Cushing's disease. Twenty-four patients with active Cushing's disease were evaluated both before and after transsphenoidal pituitary surgery (TSS); these patients were followed up for 1-36 months. Ten patients were studied only after a long-term period (1-19 years, median 4 years) after TSS (six patients), TSS plus external pituitary irradiation (three patients) and TSS plus radiosurgery (one patient). RESULTS: In 24 patients with active Cushing's disease a significant ACTH/cortisol response (P<0.001) was induced by either desmopressin (ACTH from a baseline of 15.3+/-2.7 pmol/l to a peak of 40.9+/-7.3 pmol/l; cortisol from 673+/-59 nmol/l to 1171+/-90 nmol/l) or CRH (ACTH from a basal of 14. 2+/-2.5 pmol/l to a peak of 47.2+/-7.7 pmol/l; cortisol from 672+/-50 nmol/l to 1192+/- 80 nmol/l). In all patients a positive cortisol response to desmopressin was found. After pituitary adenomectomy the 14 'cured' patients were followed up for 1-36 months; desmopressin administration never induced ACTH or cortisol responsiveness in any patient. In contrast, a progressive recovery of ACTH and cortisol responses after CRH was observed at different intervals of time in all patients but one. Five patients, in whom the cortisol concentration only normalized after surgery, showed a persistent responsiveness to desmopressin, and two of them relapsed 12 and 24 months later. In five patients who were not cured, the hormonal responsiveness to either CRH or desmopressin was similar before and after operation. Of 10 patients studied only after long-term follow-up, six were cured and a normal response to CRH was present, whereas no changes in ACTH/cortisol concentrations were induced by desmopressin. The other four unsuccessfully operated patients underwent pituitary irradiation and showed different and equivocal hormonal responses to desmopressin and to CRH. CONCLUSIONS: During the postoperative follow-up of patients with Cushing's disease, the maintenance or the disappearance of the hormonal response may be related to the persistence or the complete removal of adenomatous corticotrophs, respectively. It is suggested that desmopressin test should be performed in the preoperative evaluation and follow-up of patients with ACTH-dependent Cushing's syndrome.