Mr. LM, a 54-year-old gentleman with an essentially unremarkable history, presents with a one-month history of abdominal cramps, that he described as intermittent and not precipitated by food or activity. He denied symptoms of nausea, vomiting, abnormal bowel movements or urinary problems. He also denied experiencing fever, chills, night sweats, or weight loss.
He underwent an abdominal ultrasound for vague abdominal cramps, which revealed multiple hepatic lesions, possibly metastatic until proven otherwise. A CT scan of the abdomen confirmed numerous lesions in the liver consistent with metastases. No adenopathy or other lesions were noted in the kidneys or bowels. A CT scan of chest and head were unremarkable.
These findings led to an ultrasound-guided liver biopsy that showed a small deposit comprised of uniform epitheloid cells, but since limited specimen precluded further assessment, the pathologist recommended a repeat biopsy. Meanwhile, imaging studies failed to reveal a primary lesion.
The patient was then referred to a surgeon to undergo gastroscopy and colonoscopy. A prepyloric polypoid lesion and sigmoid diverticulosis was noted. The biopsy of the prepyloric lesion consisted of non-acid producing gastric mucosa showing acute and chronic inflammation with some atypia that was inconclusive but was positive for Helicobacter pylori.
Laboratory data was unremarkable with a normal hemoglobin of 138 g/L, white cell count of 7.1, BUN of 4.5, serum creatinine of 113, AST of 30, ALT of 51, ALP of 73, calcium of 2.37 and negative urinalysis.
On further questioning, our patient denied any specific gastrointestinal or genitourinary symptoms or any weight loss. He denied wheezing. He admitted to occasional episodes of transient flushing spells and light-headedness. He denied symptoms of chest pain, tightness or dyspnea.
His medications included omeprazole 20 mg a day and temazepam as required. He quit smoking 15 years ago and denied alcohol use. Physical examination was unremarkable.
Because of the history of flushing spells and the presence of unexplained hepatic metastases, 24-hour urinary 5-hydroxyindoleacetic acid [5-HIAA] was requested. The level was greatly elevated at 1,580 micromol/day (normal < 45 micromol/day). This confirmed our diagnosis.
What was it?
Mr. LM, whose case description appears on page 11, was diagnosed with carcinoid syndrome. Later, an octreotide scan showed multiple areas of focal uptake in the liver consistent with hepatic metastases. A small area of increased uptake was noted in left upper quadrant, but no obvious primary was revealed. Mr. LM was referred to an oncologist for further management.
Classic carcinoid syndrome, caused by the release of bioactive compounds secreted by a tumour into the systemic circulation, occurs in fewer than 10% of patients with carcinoid tumours. Most of these have a midgut carcinoid tumour. Many people with carcinoid tumours have no symptoms, or present with symptoms that have broad differential diagnoses. The small intestine is the most frequent location with two-thirds of carcinoid tumours occurring somewhere in the gastrointestinal system, followed by the lungs/bronchi. Carcinoid tumours are classified on the basis of their embryologic origin: foregut (lungs, bronchi, stomach); midgut (small intestine, appendix, proximal large bowel); and hindgut (distal large bowel, rectum). Tumours from each of these origins differ clinically, biochemically and histologically.
Carcinoid tumours secrete several bioactive compounds, including serotonin and bradykinin, and the secretory pattern varies depending on the location of the tumour. Most foregut carcinoid tumours secrete low levels of serotonin, being deficient in the enzyme needed to convert 5-hydroxytryptophan to serotonin. Midgut tumours secrete high levels of serotonin, whereas most hindgut tumours do not secrete 5-hydroxytryptophan or serotonin. These differences in secretory patterns are responsible for the various clinical manifestations and biochemical characteristics of these tumours.
The systemic effects of the bioactive compounds secreted by carcinoid tumours are responsible for carcinoid syndrome, which has features that can include bronchospasm (possibly mediated by serotonin or bradykinin), diarrhea (likely mediated by serotonin), cutaneous flushing (which has multiple possible mediators), and right-sided valvular heart lesions (possibly mediated by serotonin). However, the secretory products of midgut carcinoids are normally inactivated by enzymes in the liver before they enter the systemic circulation. Thus, patients with midgut carcinoid tumours develop the carcinoid syndrome only if they have hepatic metastases.
In contrast, those with foregut (bronchial and extraintestinal) carcinoids can present with carcinoid syndrome without hepatic metastases, since their secretory products normally bypass the liver and enter the systemic circulation directly. Hindgut tumours seldom produce this syndrome, since they don’t secrete these products.
The hallmark is cutaneous flushing that typically affects the face, neck and upper body and lasts from 30 seconds to 30 minutes. This can be unprovoked, but it’s often precipitated by foods (e.g. bananas, tomatoes, eggplant, kiwi, pineapple, cheese), by alcohol consumption, by exercise, by emotional stimuli or by anesthesia.
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