Use of desmopressin in bilateral and simultaneous inferior petrosal sinus sampling for differential diagnosis of ACTH-dependent Cushing's syndrome

In a substantial proportion of patients with Cushing's syndrome, conflicting dynamic tests and the absence of radiological images make the diagnosis of an ACTH-producing source difficult. In these circumstances, the role of bilateral and simultaneous inferior petrosal sinus sampling (IPSS) for ACTH determination already is well established. This method was used in 18 patients with Cushing's syndrome to establish the source of ACTH secretion. The diagnosis of Cushing's syndrome was confirmed by elevated urinary cortisol excretion and resistance of serum cortisol to dexa-methasone suppression (2 mg/day/orally). ACTH dependency was established by a positive response to desmopressin, metyrapone, and high-dose dexamethasone suppression (8 mg/day). IPSS was carried out before and after the administration of desmopressin (DDAVP 10 mu g IV), and the gradient between petrosal sinus and peripheral venous ACTH levels was determined. Of 17 patients with evidence of Cushing's disease, 14 had a petrosal sinus to peripheral venous ACTH gradient greater than or equal to 2.0 that increased dramatically after stimulation with desmopressin, 10 mu g IV. In two of three patients with a basal gradient <2, stimulation with desmopressin increased the petrosal sinus to peripheral gradient, allowing the diagnosis of pituitary disease. Lateralization of the pituitary lesion by the interpetrosal sinus gradient was correct in only nine patients. A significant gradient was noted in two cases of corticotrope hyperplasia. IPSS with stimulation by DDAVP, like corticotropin-releasing hormone, can be used to increase the central to peripheral gradient and to improve the diagnostic power of the procedure.