Carcinoid syndrome: update on the pathophysiology and treatment

Abstract

Approximately 30-40% of patients with well-differentiated neuroendocrine tumors present with carcinoid syndrome, which is a paraneoplastic syndrome associated with the secretion of several humoral factors. Carcinoid syndrome significantly and negatively affects patients' quality of life; increases costs compared with the costs of nonfunctioning neuroendocrine tumors; and results in changes in patients' lifestyle, such as diet, work, physical activity and social life. For several decades, patients with neuroendocrine tumors and carcinoid syndrome have been treated with somatostatin analogues as the first-line treatment. While these agents provide significant relief from carcinoid syndrome symptoms, there is inevitable clinical progression, and new therapeutic interventions are needed. More than 40 substances have been identified as being potentially related to carcinoid syndrome; however, their individual contributions in triggering different carcinoid symptoms or complications, such as carcinoid heart disease, remain unclear. These substances include serotonin (5-HT), which appears to be the primary marker associated with the syndrome, as well as histamine, kallikrein, prostaglandins, and tachykinins.Given the complexity involving the origin, diagnosis and management of patients with carcinoid syndrome, we have undertaken a comprehensive review to update information about the pathophysiology, diagnostic tools and treatment sequence of this syndrome, which currently comprises a multidisciplinary approach.

TELEPRO: Patient-Reported Carcinoid Syndrome Symptom Improvement Following Initiation of Telotristat Ethyl in the Real World

“…Since the 1980s, somatostatin analog (SSA) therapy has been the first‐line medical management approach for CS symptoms and CSD . Approximately 60% of patients may be responsive to initial SSA long‐acting release (LAR) treatment, but they have shown a loss of effect over time, resulting in refractory symptoms . Other treatment options with the potential to palliate CS or delay its progression include hepatic arterial embolization and peptide receptor radiotherapy, which are generally recommended for patients with radiographic progression rather than those with symptom progression in the setting of stable disease .…”

Incidental Diagnosis of Carcinoid Disease by Intraoperative Transesophageal Echocardiography and Subsequent Discovery of a Neuroendocrine Tumor during Cardiac Surgery

“…Carcinoid syndrome is caused by the secretion of hormones and vasoactive peptides such as serotonin, histamines, and bradykinins from NETs. 1 NETs often arise in the gastrointestinal tract or bronchi, and the liver inactivates the secretions, causing most patients to be asymptomatic. 1 However, when liver metastases occur, NET secretions enter the bloodstream, producing clinical manifestations known as carcinoid syndrome, which consists of flushing, bronchospasm, rash, diarrhea, and/or hypotension.…”

“…They can present in several different ways, including carcinoid syndrome, which consists of diarrhea and flushing, effects of tumor growth such as abdominal pain or hepatomegaly, or as an incidental finding on radiographic studies. 1 …”

Update on Pathophysiology, Treatment, and Complications of Carcinoid Syndrome

“…Fibrotic complications of secreting NEN such as carcinoid heart disease and mesenteric fibrosis are the result of increased fibrosis formation within the cardiac valves and mesentery [15,45]. One of the main factors driving fibrosis formation is thought to be serotonin since these complications occur mainly in patients with raised urine 5-HIAA, a breakdown product of serotonin [45][46][47]. Figure 1 summarizes the components and growth factors in the development of fibrosis formation.…”