Clinical Presentation of Carcinoid Tumors and Pancreatic Neuroendocrine Tumors
Overall, neuroendocrine tumors (NET) are biologically and clinically heterogeneous tumors.1 The clinical presentation of carcinoid tumors and pancreatic NET (PNET) can be nonspecific and depends on the location and clinical function of the primary tumor as well as the secretion of specific hormones.1 In general, the natural history of NET consists of a long period of vague abdominal symptoms and frequent visits to the primary care practitioner.2
Hormones associated with the clinical presentation of carcinoid tumors and functional PNET include serotonin, adrenocorticotropic hormone (ACTH), insulin, glucagon, vasoactive intestinal peptide (VIP), gastrin, somatostatin, and histamine3 (Table 4). The associated signs and symptoms of functional PNET and carcinoid tumors of the foregut, midgut, and hindgut are also included in Table 4.
|Table 4. Characteristics of Secretory NET4–7|
|Origin||Organ||Hormones||Clinical Manifestations Triggered by Excess Secretion of Hormones|
Carcinoid syndrome may occur when vast quantities of hormones are released from the carcinoid when it metastases to the liver or from a non-gastrointestinal (GI) primary tumor.4 The classic "carcinoid triad" associated with the syndrome includes flushing, diarrhea, and cardiac involvement 4 (Figure 4). The hormones largely responsible for the symptoms of carcinoid syndrome are serotonin, tachykinins, and vasoactive peptides.4,5 Carcinoid tumors located in the foregut (stomach), jejunum, ileum, appendix, and right colon can present with a carcinoid syndrome.4,5,8 Patients with longstanding uncontrolled or poorly controlled carcinoid syndrome can develop symptoms of niacin deficiency, which include diarrhea, dementia, and dermatitis.9
Figure 4. Carcinoid Syndrome 5
There are 2 variants of carcinoid syndrome: gastric and bronchial.4 Gastric carcinoid syndrome presents with well-demarcated cherry-red flushing, no diarrhea, no cardiac lesions, and the increased secretion of histamine.4 Patients often present with symptoms of peptic ulcer disease.4 In bronchial carcinoid syndrome, flushing lasts hours to days.4 The patient is often disoriented, anxious, tachycardic, hypotensive, and presents with nausea, vomiting, difficulty breathing, hemoptysis, cough, and pleuritic pain.4,10
As shown in Figure 4, flushing and diarrhea are the 2 most common signs of carcinoid syndrome.
Flushing is the most common symptom of carcinoid syndrome and occurs in more than 90% of patients.4 The initial flush experienced by patients with carcinoid tumors and PNET lasts only a few minutes but extends to hours with disease progression.4 The typical flush is described as the sudden appearance of erythema in the face and neck4 (Figure 5). Flushing may be aggravated by alcohol, stress, and increased tyramine intake (red wine, chocolate).4 The presentation of flushing also varies by location of the tumor and hormonal secretion.8 Bronchial flushing is diffuse with a cyanotic coloration, and gastric flushing is reddish with a patchy distribution over the face and neck.8
Figure 5. Patient with Flushing
Image courtesy of Rodney F. Pommier, MD, Division of Surgical Oncology, Oregon Health & Science University, Portland, OR.
Diarrhea occurs in 78% of patients with carcinoid syndrome and may be accompanied by colicky abdominal pain.4,5 The diarrhea can be severe and debilitating with up to 30 episodes of loose stools per day having been reported.4,5 Steatorrhea occurs in 67% of patients.8 Increased GI motility due to excess serotonin secretion, tumor-related partial small-bowel obstruction, short-gut syndrome due to tumor resection, intestinal ischemia, and GI malabsorption are all multiple causes of diarrhea in patients with carcinoid syndrome.4 The diarrhea of carcinoid syndrome occurs independently of flushing.4
Carcinoid Heart Disease
Carcinoid heart disease occurs in approximately two-thirds of patients with carcinoid syndrome.11 Ten percent to 30% of patients with carcinoid syndrome develop cardiac complications, such as tricuspid regurgitation or pulmonary stenosis.3 Ten percent to 20% of patients with carcinoid syndrome already have heart disease at presentation.1
The occurrence of carcinoid heart disease is directly related to circulating levels of serotonin and 5-hydroxyindoleacetic acid (5-HIAA).12 Plasma serotonin levels have been shown to be >2-fold higher and urinary 5-HIAA levels almost 4-fold higher in patients with carcinoid heart disease.12