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Shifting Paradigms in the Pathophysiology and Treatment of Carcinoid Crisis

  • Endocrine Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Carcinoid crisis is a potentially fatal condition characterized by various symptoms, including hemodynamic instability, flushing, and diarrhea. The incidence of carcinoid crisis is unknown, in part due to inconsistency in definitions across studies. Triggers of carcinoid crisis include general anesthesia and surgical procedures, but drug-induced and spontaneous cases have also been reported. Patients with neuroendocrine tumors (NETs) and carcinoid syndrome are at risk for carcinoid crisis. The pathophysiology of carcinoid crisis has been attributed to secretion of bioactive substances, such as serotonin, histamine, bradykinin, and kallikrein by NETs. The somatostatin analog octreotide has been considered the standard of care for carcinoid crisis due to its inhibitory effect on hormone release and relatively fast resolution of carcinoid crisis symptoms in several case studies. However, octreotide’s efficacy in the treatment of carcinoid crisis has been questioned. This is due to a lack of a common definition for carcinoid crisis, the heterogeneity in clinical presentation, the paucity of prospective studies assessing octreotide efficacy in carcinoid crisis, and the lack of understanding of the pathophysiology of carcinoid crisis. These issues challenge the classical physiologic model of carcinoid crisis and its common etiology with carcinoid syndrome and raise questions regarding the utility of somatostatin analogs in its treatment. As surgical procedures and invasive liver-directed therapies remain important treatment modalities in patients with NETs, the pathophysiology of carcinoid crisis, potential benefits of octreotide, and efficacy of alternative treatment modalities must be studied prospectively to develop an effective evidence-based treatment strategy for carcinoid crisis.

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Fig. 1

adapted from Ferrari et al. 114 under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0/)

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Funding

Professional medical writing and editing assistance was provided by Stephanie Agbu, PhD, of ApotheCom (Yardley, PA, USA); this support was funded by Lexicon Pharmaceuticals, Inc. (The Woodlands, TX, USA) and TerSera Therapeutics, LLC (Deerfield, IL, USA).

Author information

Authors and Affiliations

  1. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Jessica E. Maxwell MD, MBA

  2. Banner MD Anderson Cancer Center, Phoenix, AZ, USA

    Boris Naraev MD, PhD & Michael A. Choti MD

  3. Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Daniel M. Halperin MD

  4. Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA

    Thorvardur R. Halfdanarson MD

  5. Mayo Clinic Cancer Center, Rochester, MN, USA

    Thorvardur R. Halfdanarson MD

Authors
  1. Jessica E. Maxwell MD, MBA
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  2. Boris Naraev MD, PhD
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  3. Daniel M. Halperin MD
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  4. Michael A. Choti MD
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  5. Thorvardur R. Halfdanarson MD
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Corresponding author

Correspondence to Thorvardur R. Halfdanarson MD.

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Disclosure

Jessica E. Maxwell has served as a consultant for Ipsen Biopharmaceuticals. Boris Naraev has served as a consultant for Advanced Accelerator Applications, a Novartis Company; Ipsen Biopharmaceuticals; Lexicon Pharmaceuticals, Inc.; Novocure; and Sun Pharma. Daniel M. Halperin has served as a consultant for Advanced Accelerator Applications, a Novartis Company; Curium; Ipsen; Isotopen Technologien München AG; and Lexicon Pharmaceuticals, Inc.; and has received research support from Advanced Accelerator Applications, a Novartis Company; Incyte; Roche/Genentech; Tarveda Therapeutics; TerSera Therapeutics, LLC; and ThermoFisher Scientific. Michael A. Choti reports nothing to disclose. Thorvardur R. Halfdanarson has served as a consultant for Advanced Accelerator Applications, a Novartis Company; Curium; Isotopen Technologien München AG; Ipsen Biopharmaceuticals; Lexicon Pharmaceuticals, Inc; and Terumo; and has received research support from Advanced Accelerator Applications, a Novartis Company; Ipsen Biopharmaceuticals; and ThermoFisher Scientific.

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Maxwell, J.E., Naraev, B., Halperin, D.M. et al. Shifting Paradigms in the Pathophysiology and Treatment of Carcinoid Crisis. Ann Surg Oncol 29, 3072–3084 (2022). https://doi.org/10.1245/s10434-022-11371-0

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