Cushing's syndrome in patients with the Zollinger-Ellison syndrome

Reports of Cushing's syndrome in patients with the Zollinger-Ellison syndrome are rare, although up to 30 percent of gastrinomas contain ACTH-like immunoreactivity. We prospectively examined 75 patients with the Zollinger-Ellison syndrome for Cushing's syndrome. Three of 59 patients (5 percent) with the sporadic form of the Zollinger-Ellison syndrome had Cushing's syndrome, with severe symptoms due to ectopic production of ACTH. Each of these patients had metastatic gastrinoma, responded poorly to chemotherapy, and died within three years of the diagnosis of both syndromes. Three of 16 patients (19 percent) with the Zollinger-Ellison syndrome and multiple endocrine neoplasia type 1 had Cushing's syndrome due to pituitary production of ACTH, and their symptoms were mild. The gastrinoma in these patients was localized, and the prognosis was excellent. Thus, Cushing's syndrome is more common in patients with the Zollinger-Ellison syndrome than was previously reported, occurring in 8 percent of all cases. Furthermore, Cushing's syndrome in patients with sporadic Zollinger-Ellison syndrome and in those with multiple endocrine neoplasia type 1 differ in incidence, cause, clinical severity, extent of gastrinoma, the need for therapy, and prognosis. All patients with the Zollinger-Ellison syndrome and all patients with multiple endocrine neoplasia type 1 should be screened for Cushing's syndrome.