What is carcinoid syndrome?

Carcinoid syndrome is a group of symptoms some patients may present when they have a specific type of cancer called a neuroendocrine tumor, or NET. NETs are a rare, slow-growing type of cancer – they only represent about 1% of all cancers – and can occur in any number of places in the body, most often in the digestive tract.

Not all neuroendocrine tumors cause carcinoid syndrome, but it commonly develops if the NET spreads from the small bowel (or other locations) to the liver. In these cases, the hormones the NET secretes cannot be filtered out by the liver as they normally would, so they get into the body’s circulatory system and cause the symptoms of carcinoid syndrome.1

A Doctor's Voice

Providing hope and options for people seeking therapies for rare diseases has been my passion for over 15 years. My experience with medicine and drug development is aligned with Crinetics' remarkable insights and expertise in rare endocrine diseases. We mutually share a long-term commitment to serving patients experiencing these diseases and developing life-saving products to meet their needs.

— Hjalmar Lagast, MD

Pathophysiology


Seventy percent of NETs are found in the digestive tract and 25% originate in the lungs. Other possible locations include the pancreas, adrenal glands, ovaries, testes, and kidneys.

NETs derive from enterochromaffin cells (ECCs), which are found in the digestive tract, primarily in the small intestine, colon, and appendix.2  ECCs play a large role in gastrointestinal regulation, intestinal motility, and secretion.3  The substances they secrete are called humoral factors (meaning they are transported by the circulatory system), and include about 40 different polypeptides, biogenic amines, and prostaglandines. The most common of these are serotonin, histamine, tachykinins, kallikrein, and PG (prostaglandin).4

As most NETs originate in the gastrointestinal (GI) tract, substances produced by these tumors have to pass through the liver to reach the systemic circulation. In the liver, most of these substances are broken down and inactivated. For this reason, NETs originating in the GI tract do not present with carcinoid syndrome. When it does occur, the substances causing the carcinoid syndrome are produced not by the original tumor but by metastasis, that bypass the liver filtration.

Epidemiology


Prevalence (U.S.)

About 33,000 patients8

Survival

5-year survival of 30-70% (grade 1 and 2 NETs) 8

Perspective

Most studies: 10% of NETs result in carcinoid syndrome1
One major study reported up to 19%.10

About Carcinoid Syndrome


Flushing

This is the clinical hallmark of carcinoid syndrome and occurs in 85% of NETs patients5 who experience symptoms of carcinoid syndrome. Flushing is a sudden, intense  reddening of the skin with a warming and/or burning sensation of the face, head, and upper chest. These episodes occur spontaneously and can last anywhere from 30 seconds to 30 minutes, but they can also be provoked by eating, drinking alcohol, coffee, spices, or experiencing an emotional event. Severe flushes are accompanied by a fall in blood pressure and a rise in pulse rate. Many people experience excessive tearing. As the disease progresses, these episodes may last longer and become more diffuse.

Timely diagnosis of carcinoid syndrome is often difficult. Frequent diarrhea usually sends patients to a gastroenterologist. When a patient wheezes and gasps for air, they will go to a pulmonologist. Someone may see a variety of specialists over the course of several years before finally getting a proper diagnosis.

As with any rare disease, awareness is the starting point in reaching the correct diagnosis soon. The occurrence of episodic facial flushing and/or chronic diarrhea not diagnosed by standard tests as being a result of more common causes should lead to suspicion of carcinoid syndrome. Definitive diagnosis, however, is best achieved with a multimodality approach, which may include any of the following.

Many of the major symptoms of carcinoid syndrome tend to be on the dramatic side. Spontaneous-onset of flushing episodes, during which some patients report “feeling on fire.” Frequent diarrhea that can hit anytime, anywhere. Difficulty breathing, which as any asthma sufferer can attest, induces a panicked feeling.

These daily challenges often cause a great deal of stress for patients. Not knowing where, why, or when the next episode will hit can severely inhibit social interaction, which can lead to a sense of isolation. In undiagnosed patients, these episodes can cause alarm for one’s health, and can lead to frustration if not recognized for what they are.

Because it is so rare, carcinoid syndrome is often not detected or even suspected when someone presents with symptoms. Keeping it in mind as a possibility will go a long way to getting patients the treatment they need, sooner. Access to treatment is also critical, and marked by successive steps which are followed according to the efficacy of each option.

Crinetics is developing paltusotine for the treatment of NETs and carcinoid syndrome. Paltusotine establishes a new class of oral, selective, nonpeptide, somatostatin receptor type 2 (SST2) agonists. This once-daily oral investigational treatment is the first agent in its class with reported clinical trial results for the treatment of acromegaly. It is well-tolerated in acromegaly patients to date, with side effects similar to SSA therapies.

Crinetics is intently focused on empowering patients with carcinoid syndrome who are eager to be heard and who are seeking better treatment options, as well as all healthcare practitioners, to recognize the symptoms of carcinoid syndrome, diagnosis this rare disease, and implement the best course of treatment to control it.

We encourage you to establish connection with the following organizations to continue raising your awareness so that these vastly underserved patients can realize brighter futures. And, by all means, tell them Crinetics sent you.

The Final Word


Carcinoid syndrome is complex, rare disease that warrants greater awareness, and Crinetics is dedicated to making that happen. Your reading this web page is the first step in reaching our goal. If you’ve come this far, we appreciate you and we have a few final asks:

Keep carcinoid syndrome in your mental Rolodex of possible diagnoses. If you’re a patient, tell your doctor everything you’re experiencing.

Listen to patients who present with the telltale symptoms. Patients should be forthright with all of their healthcare providers.

Be the one who diagnoses it because you knew.

Prescribe your patients the treatments that can help them feel better.

Spread the word about this disease’s signs and symptoms.

Connect with medical associations and patient groups to keep on top of the latest treatments. If you suffer from carcinoid syndrome, you can tap into a support network with helpful resources.

Let’s work together to ensure underserved patients benefit from Better therapies for Better lives.

Contact


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    1. NORD; National Organization for Rare Disorders
    2. Graeme-Cook, Fiona (2009). “Neuroendocrine Tumors of the GI Tract and Appendix”. In Odze, Robert D.; Goldblum, John R. (eds.). Surgical Pathology of the GI Tract, Liver, Biliary Tract, and Pancreas. pp. 653–80. doi:10.1016/B978-141604059-0.50028-XISBN 978-1-4160-4059-0.
    3. Bertrand, Paul P.; Bertrand, Rebecca L. (2010). “Serotonin release and uptake in the gastrointestinal tract”Autonomic Neuroscience153 (1–2): 47–57. doi:10.1016/j.autneu.2009.08.002PMID 19729349S2CID 25355291.
    4. Current status of gastrointestinal carcinoids. Modlin IM, Kidd M, Latich I, Zikusoka MN, Shapiro MD. Gastroenterology. 2005;128(6):1717.
    5. Up To Date; Clinical features of carcinoid syndrome; Jonathan R. Strosberg, MD, April 15, 2019.
    6. Clinical presentation and prognosis of gastrointestinal carcinoid tumours. Sjöblom SM. Scand J Gastroenterol. 1988;23(7):779.
    7. Up To Date; Treatment of the carcinoid syndrome; Jonathan R. Strosberg, MD, March 1, 2020.
    8. Arvind Dasari, MD, MS; Chan Shen, PhD; Daniel Halperin, MD; Bo Zhao, MS; Shouhao Zhou, PhD; Ying Xu, MD; Tina Shih, PhD; James C. Yao, MD (2017). “Trends in the Incidence, Prevalence, and Survival Outcomes in Patients With Neuroendocrine Tumors in the United States”. JAMA Oncology
    9. Tetsuhide Ito, Lingaku Lee, Robert T. Jensen (2017). “Carcinoid syndrome: recent advances, current status and controversies”. Wolters Kluwer Health, Inc.
    10. Halperin DM, Shen C, Dasari A, et al. Frequency of carcinoid syndrome at neuroendocrine tumour diagnosis: a population-based study. Lancet Oncol 2017; 18:e300.
    11. Kvois LK, Moertel CG, O’Connell MJ, Schutt AJ, Rubin J, Hahn RG. “Treatment of the malignant carcinoid syndrome. Evaluation of a long-acting somatostatin analogue.” N Engl  Med. 1986,315(11):;663.
    12. Vinik AI, Woltering EA, Warner RR et al. NANETS consensus guidelines for the diagnosis of neuroendocrine tumor. Pancreas 2010; 39(6):713-734.
    13. Modlin IM, Pavel M, Kidd M, Gustafsson BI. Review article: somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine (carcinoid) tumours. Aliment Pharmacol Ther 2010; 31(2):169-188.