Pancreatic Neuroendocrine Tumor Symptoms and Side Effects 

Pancreatic neuroendocrine tumors can cause life-threatening symptoms from both hormone hypersecretion (over production) as well as tumor growth and invasion.

Pancreatic neuroendocrine tumors may be asymptomatic; however, as the tumors grow they can cause obstructive symptoms or symptoms from growth and invasion of surrounding tissue.

Obstructive Symptoms 

Individuals with pancreatic neuroendocrine tumors may experience symptoms such as abdominal pain, nausea, and vomiting, even though diagnostic scanning shows nothing. Many individuals diagnosed with liver metastases have reported having undiagnosed abdominal pain for several years prior to their diagnosis. 

Carcinoid Syndrome

Pancreatic neuroendocrine tumors can secrete a variety of hormones which can cause many clinical symptoms such as flushing and diarrhea.  Symptoms occurring together may be classified as a syndrome.

Typical Carcinoid Syndrome

Typical Carcinoid Syndrome is the most common form of Carcinoid Syndrome and is most often caused by midgut carcinoids that have metastasized to the liver.  Excess serotonin is the hormone most frequently related to Carcinoid Syndrome. The syndrome is characterized by brief episodes of flushing, diarrhea, cough, wheezing, shortness of breath, heart disease, and in rare cases, pellagra.  Flushing and diarrhea are the two main symptoms that are associated with Carcinoid Syndrome. Diarrhea can be mild to severe which may lead to weight loss and life style changes. The flushing may be light pink to a deep red and occurs in the face and in the nipple-line. It may be triggered by stress, alcohol, exercise and certain types of foods.

Carcinoid Crisis

Individuals with Carcinoid Syndrome can also experience Carcinoid Crisis which can occur spontaneously or be stress induced. A Carcinoid Crisis can be a life-threatening event that requires careful monitoring. Symptoms of a Carcinoid Crisis may include severe hypotension or hypertension, irregular and/or rapid heartbeat, wheezing, prolonged flushing, severe dyspnea (shortness of breath), and peripheral cyanosis (lack of oxygenated blood).

Carcinoid Heart Disease

Pancreatic neuroendocrine tumors can secrete a variety of hormones and vasoactive substances such as serotonin.  When these substances are released from liver metastases, the right side of the heart is exposed to them.  As a result, patients may experience Carcinoid Heart Disease characterized by plaque lesions in the right side of the heart.  Carcinoid Heart Disease can cause right-sided heart failure (Moller, Connolly, Rubin, Seward, Modesto, & Pellikka, 2003).  Carcinoid Heart Disease is most common on the right side of the heart but can also occur on the left side (Tomassetti, Migliori, Lalli, Campana, Tomasetti, Cordinaldesi, 2001).  While serotonin production is related to development of Carcinoid Heart Disease, there is evidence of increased cardiac lesions during somatostatin analog therapy (Moller et al., 2003).  All neuroendocrine tumor patients should be familiar with Carcinoid Heart Disease and discuss appropriate monitoring with their physician.  For more information on Carcinoid Heart Disease, please visit CFCF’s Expert Interview with Heidi Connolly.

Cushing’s Syndrome

Certain pancreatic neuroendocrine tumors can secrete adrenocorticotropic hormone (ACTH) causing Cushing’s Syndrome. Cushing’s Syndrome is characterized by excessive upper body weight gain, skin disorders (bruising and poor healing), baldness, and psychological disorders such as depression and anxiety. 

Zollinger-Ellison Syndrome

Gastrinomas hypersecrete (over produce) gastrin causing Zollinger-Ellison Syndrome. Symptoms of Zollinger-Ellison Syndrome include diarrhea and peptic-ulcers.  Patients with Zollinger-Ellison Syndrome may also develop gastric carcinoid as a result of prolonged gastrin hypersecretion.

Verner Morrison Syndrome 

VIPomas hypersecrete Vasoactive Intestinal Peptide (VIP) which causes Verner-Morrison Syndrome.  Symptoms of Verner-Morrison Syndrome include severe watery diarrhea, which can be life threatening.

Insulinoma Syndrome 

Insulinomas hypersecrete insulin and pro-insulin which causes confusion, sweating, dizziness, weakness and unconsciousness (Ramage, Ahmed, Ardill, Bax, Breen, Caplin, Corrie, Davar, Davies, Lewington, Meyer, Newell-Price, Poston, Reed, Rockall, Steward, Thakker, Toubanakis, Valle, Verbeke, Grossman, and UK and Ireland Neuroendocrine Tumor Society, 2012; Tomassetti et al., 2001).  Prolonged hypoglycemia (low blood sugar) can have permanent impact on brain function.

Glucagonoma Syndrome

Glucagonomas hypersecrete glucagon which causes skin rash, diabetes, and weight loss.

References

Kulke, M. H. (2007). Clinical Presentation and Management of Carcinoid Tumors. Hematology/Oncology Clinics of North America, 21, 433-455. Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/17548033. 

Moller, J. E., Connolly, H. M., Rubin, J., Seward, J. B., Modesto, K., Pellikka, P. A. (2003).  Factors associated with progression of carcinoid heart disease. New England Journal of Medicine, 13(348), 1005-1015. Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/12637610.

Ramage, J., Ahmed, A., Ardill, J., Bax, N., Breen, D.J, Caplin, M.E., Corrie, P., Davar, J., Davies, A.H., Lewington, V., Meyer, T., Newell-Price, J., Poston, G., Reed, N., Rockall, A., Steward, W., Thakker, R.V., Toubanakis, C., Valle, J., Verbeke, C., and Grossman, A.B., and UK and Ireland Neuroendocrine Tumor Society (2012) . Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs). Gut, 61(1):6-32. Retrieved from: www.ncbi.nlm.nih.gov/pubmed/22052063. 

Tomasseti, P., Migliori, M., Lalli, S., Campana, D., Tomassetti, V., Corinaldesi, R. (2001). Epidemiology, clinical features and diagnosis of gastroenteropancreatic endocrine tumours. Annals of Oncology, 12(2), S95-S99. Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/11762360.