Case Report: Pancreatic neuroendocrine tumor with ectopic ACTH-production upon second recurrence

A 54-year-old woman suffered from diarrhoea, heartburn and unspecific abdominal pain. A tumor in caput pancreatis with metastases in lymphatic nodules was diagnosed and completely resected. The histological diagnosis was carcinoid. Fourteen months after surgery abdominal CT and somatostatin-receptor scintigraphy suggested relapse of the tumor. At this time the patient reported no symptoms. Laboratory values were all in the normal range. A second in toto resection was performed. Histological investigation confirmed relapse of the pancreas carcinoid without metastases. Eight months later the patient suffered from adynamia, mental disorder, muscle weakness, weight loss, plethora and developed diabetes mellitus. Further laboratory investigation showed hypokalemia, increased serum cortisol, 24h-urinary cortisol and ACTH. Subsequent endocrinological testing revealed no suppression of 8.00 a.m. serum cortisol after administration of low-dose dexamethasone as well as lack of suppression of 8.00 a.m. serum cortisol after high-dose dexamethasone. ACTH remained high and did not rise further after injection of CRH. Therefore an ectopic ACTH production was supposed. The search for a focus of ectopic ACTH production disclosed an intensive enhancement of the tracer ventro-medial of the left kidney in octreotid scintigraphy. In abdominal MRI a tumor of 3×4x5cm size lateral of the superior mesenteric artery was seen. A rest-pancreatectomy with splenectomy and left-side adrenalectomy was performed. The pathological diagnosis was a second relapse of the pancreatic neuroendocrine carcinoma without metastases. In contrast to the primary tumor and the first relapse, immunostaining of tissue for ACTH was strongly positive. This is to our knowledge the first case describing a pancreatic neuroendocrine tumor which started to produce ACTH de novo at the time of the second relapse after two complete tumor resections. The case underscores the importance of keeping in mind a possible hormone shift of neuroendocrine tumors even after complete tumor resection and in the absence of metastases.