Carcinoid Syndrome and Carcinoid Crisis

Although no consensus definition has been reached, carcinoid crisis is a dreaded phenomenon of life-threatening hemodynamic instability that can occur during times of tumor manipulation, most commonly intraoperatively, although also during other invasive procedures. Due to the known production of vasoactive substances by neuroendocrine tumors, carcinoid crisis was historically thought to be an extension of carcinoid syndrome, which is thought to occur due to the release of vasoactive amines and peptides that are able to bypass portal circulation via hepatic metastases, drain directly into systemic circulation via ovarian or pulmonary metastases, or overwhelm the portal degradation system by sheer volume. However, recent studies have questioned this paradigm by showing that crisis can occur in patients without carcinoid syndrome or hepatic metastases, and in the only prospective study of crisis, there was no spike of hormones seen during crises. As such, the use of octreotide (a somatostatin analogue that causes inhibition of hormone release) for the prevention and treatment of carcinoid crises has become controversial. In addition, the use of β-adrenergic agonists was historically thought to cause precipitation of secondary carcinoid crisis, but this has also been disproven. Very few studies exist on this topic, with current recommendations from specialty societies relying on expert opinion and recognizing that this is an area of uncertainty. Our current recommendation is to recognize that all patients with carcinoid tumors are at risk of crisis, and to be ready to treat these crises with rapid infusion of intravenous fluids, vasopressin, phenylephrine, and β-adrenergic agonists. Much remains to be learned about the treatment of carcinoid crisis, and we also recommend future studies on the pathophysiology of this unique and rare endocrine emergency.