When poorly controlled carcinoid syndrome is suspected, especially when diarrhea is the predominant symptom, the very first step is to make sure that the diarrhea is, in fact, from carcinoid syndrome. Many patients with carcinoid syndrome undergo terminal ileal resection, as the terminal ileum is a common site for the primary neuroendocrine tumors that can lead to carcinoid syndrome, and this procedure can result in bile acid diarrhea. It is fairly simple to measure the bile acids or to give bile acid sequestrant therapy (eg, cholestyramine) empirically. Additionally, patients who have had an ileocecectomy, with removal of the ileocecal valve, are also at risk for small bowel bacterial overgrowth as a mechanism for worsening diarrhea, in which case antibiotic therapy may be helpful. And some individuals may develop exocrine pancreatic insufficiency and steatorrhea from the SSAs themselves. These are all relatively common masqueraders of worsening carcinoid syndrome.

Clinical clues can help to differentiate between these entities. Symptoms that worsen within the first few days or during the first week of SSA therapy and later resolve may suggest that pancreatic enzyme replacement therapy could be appropriate. In contrast, worsening symptoms 3 to 4 weeks after the long-acting SSA injection suggest that the therapeutic effect is not lasting the entire 4-week interval between the SSA doses and that carcinoid syndrome symptom control is therefore waning.

There are several strategies for improving carcinoid syndrome symptom control. Maximizing simple supportive care (eg, with loperamide or diphenoxylate-plus-atropine therapy) can sometimes improve the patient's diarrhea. If the problem is related to the duration of control month to month with long-acting SSA therapy, then it may be possible to either decrease the dosing interval of the long-acting SSA to every 3 weeks or give short-acting octreotide up to 3 times per day during that final week to provide better control. Short-acting octreotide can also be used to supplement long-acting octreotide as a management strategy on an ongoing basis. Further, it is reasonable to try telotristat in combination with SSAs. Telotristat can be quite helpful at times and is less helpful for other patients.

Despite these relatively simple interventions, some patients with carcinoid syndrome continue to have a significant symptom burden. In patients who have significant disease bulk in the liver and uncontrolled carcinoid syndrome, some type of liver-directed therapy, whether it be surgery or an arterial embolic therapy, can often be quite helpful. Some individuals may be candidates for surgical procedures to remove a significant amount of metastatic disease in the liver, which can improve symptoms dramatically. It is hoped that this may also lead to improved overall survival, although no randomized trial can be done to prove this. Hepatic arterial embolic therapy can often improve carcinoid syndrome symptoms as well. Finally, peptide receptor radionuclide therapy with lutetium-177–DOTATATE is another option to consider in patients with somatostatin receptor–positive neuroendocrine tumors and carcinoid syndrome.