Overview of chronic diarrhea caused by functional neuroendocrine neoplasms

Eight different neoplastic disorders can cause chronic diarrhea attributable to humoral-mediated diarrhea. These include pancreatic endocrine tumor (PET) syndromes (gastrinomas, VIPomas, glucagonomas, somatostatinomas, PET's releasing calcitonin), carcinoid syndrome, medullary thyroid cancer, and systemic mastocytosis. Because these disorders are an uncommon cause of all chronic diarrheas (<1%), they are not often considered in the differential diagnosis, leading to a delay in diagnosis. This is problematic not only because all are treatable, but also because the neoplasm is frequently malignant. In this article, the characteristics and pathogenesis of the diarrhea, important clinical and diagnostic laboratory features, and treatment of each disorder are briefly reviewed, with an emphasis on recent insights.