a) A 62-year-old woman has been admitted to hospital for investigation, giving a history of episodic facial flushing and diarrhoea, and fatigue. You are called to review her on the ward because she is hypotensive. Your examination shows features of right heart failure, with a tricuspid regurgitant murmur.
- Normal LV size and systolic function.
- The right ventricle is dilated, with normal systolic function.
- Triscuspid valve leaflets are thickened, retracted, and relatively immobile.
- There is severe tricuspid regurgitation.
- Pulmonary valve leaflets are thickened.
- Mild pulmonary regurgitation.
- Other valves are normal.
i. What is the most likely diagnosis?
ii. What is the most useful investigation to confirm this diagnosis?
i. Diagnosis: Carcinoid syndrome with cardiac involvement
ii. Investigation: 24 hour urinary HIAA (5-hydroxyindoleacetic acid) OR Serum chromogranin-A
This sadistic question separates the wheat from the chaff.
Is there any wonder the pass rate was only 10%?
Carcinoid syndrome is freakishly rare. One ought to feel no remorse at knowing little about it, because in the course of one's medical practice one might never bump into one of these.
However, the facial flushing is a dead giveaway.
First described as a "unique syndrome" of facial flushing and elevated serotonin, carcinoid syndrome has become grouped together with all the other sorts of syndromes of malignant origin, particularly of neuroendocrine tumours. Carcinoid tumours are slowly growing neuroendocrine tumours of upper GI origin; indeed the term "carcinoid" refers to the fact that they are only carcinoma-like.
Additionally, the presence of facial flushing AND right heart valve damage is pathognomonic.
Its just a pattern one learns to recognise.
The damage is typically to the valve structures, and is typically a sclerosis, resulting in right heart failure. The mechanism is thought to be an effect of the vasoactive substances secreted by the tumour on the myocardium, resulting in fibrotic changes.
As for the diagnosis...
Twenty-four-hour measurement of urinary 5-hydroxyindole-3-acetic acid (5-HIAA), which is the degradation product of serotonin, is apparently 88% specific for serotonin-producing carcinoid tumours.
The MJA article cautions that tryptophan/serotonin-rich foods (bananas, avocados, plums, eggplants, tomatoes, plantains, pineapples and walnuts) can produce a falsely elevated 5-HIAA level.
Serum chromogranin-A is a much better test, because it is more reliable, does not require 24 hours of urine collection, and can be later used to monitor treatment.
Oates, John A., and Albert Sjoerdsma. "A unique syndrome associated with secretion of 5-hydroxytryptophan by metastatic gastric carcinoids." The American journal of medicine 32.3 (1962): 333-342.1
Lundin, L., et al. "Carcinoid heart disease: relationship of circulating vasoactive substances to ultrasound-detectable cardiac abnormalities." Circulation 77.2 (1988): 264-269.
Modlin, Irvin M., et al. "Gastrointestinal neuroendocrine (carcinoid) tumours: current diagnosis and management." Med J Aust 193.1 (2010): 46-52.
Stridsberg, Mats, et al. "Measurements of chromogranin A, chromogranin B (secretogranin I), chromogranin C (secretogranin II) and pancreastatin in plasma and urine from patients with carcinoid tumours and endocrine pancreatic tumours." Journal of Endocrinology 144.1 (1995): 49-59.