"If the usual diagnostic tests [for IBS or other common GI disorders]—such as colonoscopy and upper endoscopy with the relevant biopsies—are unrevealing, this should raise the possibility of carcinoid syndrome, although it must be remembered that IBS is far more common than carcinoid syndrome." –Dr David C Metz
Carcinoid syndrome is believed to be caused by neurohormonal products, including serotonin, substance P, corticotrophin, histamine, dopamine, neurotensin, prostaglandins, kallikrein, and tachykinins, which can be released by an underlying tumor.2 It occurs in approximately 8% to 35% of patients with NETs.1 The most common signs and symptoms of carcinoid syndrome are flushing, diarrhea, abdominal cramping, and cardiac disease caused by valvular heart lesions.3 Some experts suggest that symptoms may be exacerbated by The 5 E's: eating, epinephrine, emotion, ethanol, and exercise.4,5
Adapted from Creutzfeldt W. World J Surg. 1996;20(2):126-131.
Focus: Four key symptoms of carcinoid syndrome
Chronic diarrhea and carcinoid syndrome
Chronic diarrhea is present in up to 80% of patients with carcinoid syndrome.3,6 There are many causes of chronic diarrhea7; however, certain characteristics may help associate this symptom with carcinoid syndrome and aid in a differential diagnosis.
The stools in diarrhea associated with carcinoid syndrome are watery and result from intestinal hypermotility and hypersecretion.3 The increase in gut motility in patients with carcinoid syndrome is likely to be caused by serotonin, which is released by certain types of NETs8 and stimulates small bowel and colonic secretions and motility.9,10
"A clue to carcinoid syndrome is that fasting does not reduce the diarrhea, because the increased motility and increased secretion are independent of intake." –Dr David C Metz
Another clue is that diarrhea may be nocturnal. Nocturnal diarrhea may be observed in other conditions (eg, IBD), but it is typically not seen in IBS.7 If IBD is suspected clinically, the patient can be evaluated endoscopically and/or radiologically. Note that there is limited information available in the literature on nocturnal diarrhea in carcinoid syndrome.11
Abdominal pain and carcinoid syndrome
Abdominal pain is a nonspecific symptom with many different potential causes. Diagnosing abdominal pain associated with carcinoid syndrome is difficult because there are no real distinguishing factors. In carcinoid syndrome, abdominal pain or discomfort may be due to gut hypermotility, obstructive-type symptoms or, rarely, intussusception of the neoplasm. Pain may also be due to serosal involvement of the neoplasm or stretching of the liver capsule because of large hepatic metastases.
Abdominal pain in carcinoid syndrome is intermittent12 and crampy,3 and occurs in approximately 40% to 51% of patients.3,8 Pain associated with diarrhea in carcinoid syndrome may be colicky9,13 and may not be relieved with defecation.14
Flushing and carcinoid syndrome
Flushing is the most common symptom of carcinoid syndrome and occurs in more than 90% of patients.9 Usually pink to red in color, flushing typically affects the face, neck, and upper trunk.8,9 Flushing in carcinoid syndrome is characteristically dry15—in women, this helps distinguish it from menopausal hot flashes, which are often associated with perspiration.16 The specific cause of flushing in carcinoid syndrome is unknown, although it has been shown to be preceded by a rise in substance P.17
Transient hypotension, headache, and bronchoconstriction may coincide with flushing in patients with carcinoid syndrome, particularly in those with foregut NETs.8 Physicians should consider that menopausal hot flashes are not associated with a fall in blood pressure.17
Cardiac disease and carcinoid syndrome
Cardiac disease is one of the most serious aspects of this disease, occurring in approximately two-thirds of patients with carcinoid syndrome.18
Cardiac manifestations usually develop late in neuroendocrine disease,9 when the right side of the heart is exposed to high levels of serotonin and other vasoactive substances released from hepatic metastases.19 This exposure is believed to result in fibrotic damage of the right heart endocardium and pulmonary and tricuspid valves.1,19,20
Left-sided heart disease is infrequent but has been observed in some patients.1,19
Carcinoid heart disease has been shown to be associated with increased levels of urinary 5-HIAA21,22 and can be detected with 2-dimensional echocardiographic and Doppler examinations.22
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