The application of a combined stimulation with CRH and desmopressin duringbilateral inferior petrosal sinus sampling in patients with Cushing's syndrome

BACKGROUND Bilateral inferior petrosal sinus sampling (BIPSS) is a useful i nvestigative technique in the differential diagnosis of ACTH-dependent Cush ing's syndrome (CS). The diagnostic sensitivity of this procedure is improv ed by the administration of CRH to stimulate ACTH secretion. It has been re ported recently that the combined administration of CRH and desmopressin is a more potent stimulus for ACTH release from corticotroph adenomas. We the refore hypothesized that the combined stimulation of ACTH secretion with CR H plus desmopressin may further improve the diagnostic outcome of this proc edure. AIMS To report our experience of the application of combined stimulation wi th CRH and desmopressin during BIPSS in patients with ACTH-dependent Cushin g's syndrome, and to compare these results to those obtained in patients wh o have undergone BIPSS with CRH stimulation alone. PATIENTS We studied 34 patients with ACTH-dependent CS: 30 with Cushing's d isease (CD) and four with occult ectopic ACTH syndrome (oEAS). A combined s timulation with CRH (100 mu g i.v.) plus desmopressin (10 mu g i.v.) during BIPSS was performed in 15 patients with CD, while in a different group of 15 patients with CD, BIPSS was performed with CRH stimulation alone (100 mu g i.v.). In the patients with oEAS, BIPSS was performed with CRH stimulati on in three and CRH plus desmopressin in one patient. RESULTS In patients with CD the mean peak ACTH levels from the dominant pet rosal sinus samples were significantly higher in the group given a combined stimulus than in the group who had only CRH stimulation (mean +/- SD: 1649 +/- 938 vs. 692 +/- 561 ng/l, P < 0.05). Dominant inferior petrosal sinus/ peripheral (IPS/P) ACTH ratios greater than 2 were observed in 15/15 (100%) patients following the combined stimulation with CRH and desmopressin and 13/15 (87%) patients undergoing stimulation with CRH alone. No patient with oEAS had an IPS/P ratio greater than 2. It is of note that the single pati ent with oEAS studied following a combined stimulation during BIPSS had a I PS/P ratio of less than 2, despite a significant peripheral ACTH and cortis ol response. CONCLUSIONS A combined stimulus using CRH and desmopressin appears to induc e a higher ACTH output from pituitary corticotroph adenomas during BIPSS, w hich may improve the diagnostic sensitivity of this procedure.