Risk factors are previous CS, elevated 5-hydroxy-indolacetic acid (5-HIAA) and/or Chromogranin A, high tumor burden, metastatic disease (mainly hepatic), carcinoid heart disease, advanced patient age, and the use of drugs that cause histamine release such as sympathomimetic and β2 agonist bronchodilators [26,27,28,29,31,32]. This evidence concerns the gene CHGA and Cowden syndrome 1.