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Fibrosis and carcinoid syndrome: from causation to future therapy

Nature Reviews Endocrinology volume 5, pages 276–283 (2009)Cite this article

Abstract

Carcinoid tumors are part of a heterogeneous group of gastrointestinal and pancreatic endocrine tumors that are characterized by their capacity to produce and secrete hormones, 5-hydroxytryptamine, tachykinins and other mediators. These substances are thought to be responsible for the collection of symptoms, which include diarrhea, flushing and wheezing, that is known as carcinoid syndrome. Fibrosis that occurs either local to or distant from the primary tumor is one of the hallmarks of carcinoid tumors that originate from the midgut. The fibrotic process can occur in the mesentery as a desmoplastic response and may lead to obstruction of the small bowel, but it can also occur in the lungs, skin or retroperitoneum. Importantly, up to one-third of patients develop cardiac valvulopathy. One or more products that are secreted by the tumor and enter into the circulation are likely to have a role in this process. This Review discusses the incidence and prevalence of fibrosis in carcinoid syndrome and explores evidence to date for causative agents, in particular the roles of 5-hydroxytryptamine and elements of the downstream signaling pathway. Improved understanding of the etiology of carcinoid-tumor-related fibrosis may lead to better treatments for this condition than those we currently have.

Key Points

  • Fibrosis that develops either local to or distant from the primary tumor is a hallmark of carcinoid tumors that originate from the midgut

  • Fibrosis is an important clinical complication of carcinoid syndrome and is associated with ischemia and obstruction in the small bowel, and cardiac valvulopathy

  • The biology of carcinoid-syndrome-related fibrosis is not fully understood, but evidence suggests that 5-hydroxytryptamine and the 5-hydroxytryptamine 2B receptor both have a role

  • Other mediators, including TGF-β and growth factors, may also be important in the development of carcinoid-syndrome-related fibrosis

  • Improved understanding of the etiology of carcinoid-tumor-related fibrosis may lead to better treatments for this condition than those we currently have

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Figure 1: Axial CT image of a calcified mesenteric mass (arrow) with indrawing of the mesentery.
Figure 2: Axial CT image of a patient with a metastatic carcinoid tumor that demonstrates retroperitoneal thickening and fibrosis (arrow).
Figure 3: Axial CT image that shows calcified mesenteric mass (arrow) with indrawing of the mesentery and appearance of misty mesentery.
Figure 4: Axial CT image of a patient with a metastatic carcinoid tumor and marked calcification within the mesenteric mass (arrow).
Figure 5: MRI scans of a patient with metastatic carcinoid tumor.
Figure 6: Serotonin synthesis pathway.

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Acknowledgements

Charles P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.

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  1. Centre for Endocrinology, Barts and the London School of Medicine, London, UK

    Maralyn Druce & Ashley B. Grossman

  2. Department of Radiology, Barts and the London School of Medicine, London, UK

    Andrea Rockall

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Druce, M., Rockall, A. & Grossman, A. Fibrosis and carcinoid syndrome: from causation to future therapy. Nat Rev Endocrinol 5, 276–283 (2009). https://doi.org/10.1038/nrendo.2009.51

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