Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about or that we otherwise haven’t been able to report on very often.
Eyes front and ears open. Class is now in session.
The disease that we will be learning about today is:
Also known as carcinoid apudoma or Thorson-Bioerck syndrome.
What is Carcinoid Syndrome?
- Carcinoid syndrome occurs when a rare cancerous tumor called a carcinoid tumor secretes certain chemicals into your bloodstream, causing a variety of signs and symptoms. Carcinoid tumors occur most commonly in the gastrointestinal tract or lungs.
- In 1888 Lubarsch first described a carcinoid tumor, but Oberndorfer called a group of small, benign-appearing tumors karzinoide tumoren (carcinoid) for the first time in 1907.
- The name was chosen to separate these tumors from ordinary malignancies (carcinomas), but by the 1950s, the fact that carcinoids could be malignant was obvious, thanks to Erspamer and Asero (1952), who identified serotonin production by carcinoid tumors.
- Carcinoid syndrome is a group of symptoms in people with neuroendocrine tumors (NETs). The symptoms are caused by too much serotonin in the gut. Carcinoid tumors are a slow-growing form of neuroendocrine tumor.
- Some of the most common symptoms of carcinoid cyndrome are diarrhea, facial flushing, and tissue fibrosis or heart valve damage. This can lead to carcinoid heart disease, which is a condition similar to heart failure in people with neuroendocrine tumors.
- Metastatic carcinoid tumors can go undiagnosed for years. It may take anywhere from 5 to 7 years before an accurate diagnosis is determined. These types of tumors are very hard to find and, sometimes, a doctor will actually discover a carcinoid tumor by accident during an appendectomy (removal of the appendix) or a routine GI endoscopy (a procedure to examine the inside of the digestive tract).
- Carcinoid syndrome affects about 1 in every 10 patients who have a carcinoid tumor, or about 14,000 Americans.
- Epidemiologic studies have reported incidences of carcinoid tumors ranging from 0.79 to 1.88 per 100,000 population; a study from the Netherlands found an incidence of 1.95 per 100,000 population. These numbers are probably underestimates, because a large number of affected individuals do not develop the related syndrome. A Swedish autopsy study reported an incidence of 8.4 cases per 100,000 population. Carcinoid tumors are discovered in approximately 1-2 appendectomy cases per 200-300 per year.
How Do You Get It?
- Carcinoid tumors occur most commonly in your gastrointestinal tract, including your stomach, small intestine, appendix, colon and rectum, or in your lungs.
- Carcinoid syndrome is caused by a carcinoid tumor that secretes serotonin or other chemicals into your bloodstream. Only a small percentage of carcinoid tumors secrete the chemicals that cause carcinoid syndrome. In most cases, the liver effectively neutralizes the chemicals before they have a chance to travel through your body and cause symptoms.
- What causes the appearance of carcinoid tumors remains unclear.
- Risk factors for carcinoid syndrome include:
- Age: Carcinoids occur most frequently in patients aged 50-70 years, though it is possible to develop them outside of this age range
- Smoking: May increase the risk of getting a carcinoid tumor of the small intestine, according to some research. But further studies are needed to confirm this.
- Multiple endocrine neoplasia type I
- This is a rare condition caused by inherited defects in the gene MEN1. People with this syndrome have a very high risk of getting tumors of 3 glands: the pituitary, parathyroid, and pancreas. They also have an increased risk of carcinoid tumors.
- Neurofibromatosis type 1
- This disease often runs in families and is characterized by many neurofibromas (benign tumors that form in nerves under the skin and in other parts of the body). It is caused by defects in the NF1 gene. Some people with this condition also develop neuroendocrine tumors of the small intestines.
What Are The Symptoms?
- It’s important to learn the signs of carcinoid syndrome, since it can sometimes be tricky to diagnose and may be confused with more common medical issues, such as IBS or menopause. Symptoms can also vary from person to person, but the most common include:
- Rapid heartbeat/damaged heart valves. Your heart feels like it’s racing, even if you’re inactive. Other symptoms can include facial lesions or rashes, difficulty breathing, joint pain, stomach pain, low blood pressure, night sweats, persistent fatigue and unexplained weight loss.
- Skin flushing. The skin—typically the face and upper torso, but sometimes the legs—develops a purplish or red hue and feels warm. It can last anywhere from a couple minutes to a few hours, and may be triggered without cause or due to stress, eating or alcohol.
- Diarrhea. Frequent (sometimes up to 20 times a day) watery stools, which may be accompanied by cramps.
- The diarrhea associated with carcinoid syndrome can have a big impact on quality of life. Patients can experience fairly profound secretory diarrhea and frequent bowel movements throughout the course of the day. It is not uncommon for people with carcinoid syndrome to have memorized the location of every rest stop along the drive from their home to the hospital.
- Diarrhea is one of the most common and life-disrupting symptoms of carcinoid syndrome. It affects nearly 80% of people with carcinoid syndrome. Even with somatostatin analog (SSA) treatment, some people continue to experience carcinoid syndrome diarrhea.
- Carcinoid syndrome diarrhea is caused by an overproduction of serotonin inside neuroendocrine tumor (NET) cells. Too much serotonin increases the amount of fluid in the gut. It also speeds up the function of the gut. This causes diarrhea, which can happen throughout the day. Short bowel syndrome, an overgrowth of bacteria in the gastrointestinal tract, and the use of SSA injections may also cause diarrhea.
How Is It Treated?
- Carcinoid syndrome is a chronic condition and a cure may not be possible, however, the symptoms can be treated with medication.
- When treating carcinoid tumors and carcinoid syndrome, your doctor is most concerned with preserving your overall health and lifestyle. The goals of treatment are to remove the carcinoid tumor or reduce its size, and to help manage its impact on you.
- Treatment options for carcinoid syndrome can include:
- Resection (removal) of primary lung carcinoids is often curative.
- For patients with hepatic metastases, surgical debulking, while not curative, may relieve symptoms and, in certain instances, prolong survival. In addition, locoregional therapies for liver metastases could include transarterial chemoembolization (TACE), bland embolization, radioembolization with yttrium-90 microspheres, and radiofrequency ablation.
- Radiation therapy is unsuccessful, in part because of the poor tolerance of normal hepatic tissue to radiation. No effective chemotherapeutic regimen has been established, but streptozocin with 5-fluorouracil is most widely used, sometimes with doxorubicin.
- Certain symptoms, including flushing, have been relieved by octreotide (which inhibits release of most hormones) without lowering urinary 5-HIAA or gastrin. Numerous studies have suggested good results with octreotide, a long-acting analog of somatostatin. Octreotide is the drug of choice for controlling diarrhea and flushing
- Case reports indicate that tamoxifen has been effective infrequently; leukocyte interferon (IFN-alpha) has temporarily relieved symptoms.
- Flushing also can be treated with phenothiazines (eg, prochlorperazine 5 to 10 mg or chlorpromazine 25 to 50 mg po q 6 h). Histamine type 2 (H2) blockers may also be used.
- Phentolamine (an alpha-blocker) 5 to 15 mg IV has prevented experimentally induced flushes. Corticosteroids (eg, prednisone 5 mg po q 6 h) may be useful for severe flushing caused by bronchial carcinoids.
- Diarrhea may be controlled by codeine 15 mg po q 4 to 6 h, tincture of opium 0.6 mL po q 6 h, loperamide 4 mg po as a loading dose and 2 mg after each loose bowel to a maximum of 16 mg/day, diphenoxylate 5 mg po qid, or peripheral serotonin antagonists such as cyproheptadine 4 to 8 mg po q 6 h.
- Niacin and adequate protein intake are needed to prevent pellagra because dietary tryptophan is diverted to serotonin by the tumor. Enzyme inhibitors that prevent the conversion of 5-hydroxytryptophanto serotonin include methyldopa 250 to 500 mg po q 6 h.