Abstract
We report a 63-year-old man who presented with breathlessness and weight loss and was diagnosed on echocardiography to have carcinoid heart disease. It was later transpired that he underwent surgical removal of an ileal carcinoid tumour 19 years previously.
Case report
A 63-year-old man presented to his general practitioner with a three-month history of dyspnoea on exertion and weight loss. On examination he had central cyanosis and a precordial pansystolic murmur. Past medical history included a right hemicolectomy for bowel cancer 19 years previously.
He was referred to cardiology, but worsening breathlessness precipitated urgent admission to hospital. Chest X-ray and electrocardiogram were unremarkable. He was initially treated for pulmonary emboli, but these were excluded following computed tomography (CT) pulmonary angiography. A subsequent echocardiogram (ECHO) demonstrated severe tricuspid regurgitation with thickened valves and restricted cusp motion, moderate pulmonary regurgitation, and enlargement of the right atrium and ventricle but normal left heart size and function. This prompted suspicion of carcinoid heart disease, which was confirmed with elevated 24 h urine 5-hydroxyindole acetic acid (5HIAA) excretion of 1478 μmol (0–50), plasma chromogranin A (CgA) of >1000 pmol/L (<60) and plasma chromogranin B (CgB) of 279 pmol/L (<150). CT of the abdomen revealed liver metastases and CT of the chest confirmed right heart enlargement. Routine clinical biochemistry and haematology investigations were within reference limits as were serum/plasma calcium, parathyroid hormone, thyroid function tests, prolactin, calcitonin, alphafetoprotein, carcinoembryonic antigen, β-human chorionic gonadotropin, gastrin, pancreatic polypepetide, vasoactive intestinal peptide, glucagon, neurotensin and somatostatin. Tumour markers were measured as recommended in Guideline for the Management of Gastroentropancreatic Neuroendocrine (including carcinoid) Tumours. 1 Histology from his hemicolectomy 19 years ago was eventually recovered, confirming a well-differentiated carcinoid tumour 4 cm in diameter, in the terminal ileum with two positive lymph nodes.
He was commenced on somatostatin analogues and referred for cardiac surgery as dyspnoea was his most pressing and disabling problem. Preoperative cardiac investigations confirmed right ventricular dysfunction, tricuspid and pulmonary incompetence but normal left ventricular function and coronary arteries. He underwent successful tricuspid and pulmonary valve replacement but developed postoperative heart block which was treated with a cardiac pacemaker. Two years following cardiac surgery he remains well and shows no evidence of breathlessness following exertion.
Discussion
Carcinoid heart disease is seen in almost 50–70% of patients with carcinoid syndrome. 2,3 However, up to 20% of patients with carcinoid syndrome present with carcinoid heart disease at diagnosis. 2 This case, however, is remarkable because the diagnosis of carcinoid heart disease was made on echocardiography in the absence of other typical clinical features of carcinoid syndrome and knowledge of a previous carcinoid tumour. It has been suggested that flushing, diarrhoea and bronchospasm in patients with right-sided heart disease should suggest the possibility of carcinoid heart disease and indeed it is very rare for carcinoid heart disease to present as isolated right-sided heart failure. 3
Carcinoid heart disease manifests itself mostly as right-sided heart disease with endocardial plaques of fibrous tissue developing on the valves and cardiac chambers. The tricuspid valve is the most commonly affected valve with a thickened appearance and incomplete coaptation resulting in moderate to severe regurgitation. The pulmonary valve is less commonly involved but may also show some thickening and retraction resulting in regurgitation and less commonly stenosis. 3 These echocardiographic features are pathognomonic of carcinoid heart in the absence of exposure to drugs like ergot-derived dopamine agonists, ergot alkaloids and appetite suppressants like fenfluramine. 2,4
There is growing evidence that serotonin plays a major role in the development of carcinoid heart disease. It increases the synthesis of transforming growth factor-β1 and connective tissue growth factor increasing collagen production by the interstitial cells in the heart valve. 5 Serotonin is metabolized in pulmonary parenchyma; therefore left-sided heart lesions are rarely seen. Exceptions are in cases of patent foramen ovale with right to left shunt; bronchial carcinoid or extensive liver metastasis leading to very high level of circulating vasoactive amines. 2
Biochemical confirmation of carcinoid syndrome includes demonstration of an elevated 24 h excretion of urinary 5HIAA (a metabolite of serotonin) and increased concentrations of plasma chromogranins. In highly selected populations, the reported sensitivity of 5HIAA is 35% while its specificity is almost 100%. 6 False-positive 5HIAA excretion may occur with drugs including paracetamol and naproxen as well as diets rich in bananas, nuts, pineapple, plums, kiwi, avocado and caffeine. 1 Chromogranin A (CgA) and chromogranin B (CgB) are general neuroendocrine tumour markers. However, CgA is considered the best marker for detecting carcinoid tumours and for monitoring disease activity. In highly selected populations, elevated CgA has a specificity of 96–84% and a sensitivity of 55–85% depending on cut-off values. 6,7 Carcinoid tumours may be associated with type 1 multiple endocrine neoplasia or other gastroentropancreatic neuroendocrine tumours.
Tumour localization and the extent of the disease are evaluated by radiological investigations including ultrasound, CT, magnetic resonance imaging and radionucleotide scanning. Carcinoid tumours have somatostatin receptors, and scanning with indium-labelled Octreotide is positive in >90% of patients with carcinoid and predicts which tumours are suitable for Octreotide therapy. 1 Cardiac involvement is best assessed by transthoracic echocardiography. 3 However, cardiac MRI may be useful when echocardiography is technically difficult. 2
The presence of carcinoid syndrome is usually indicative of extensive metastatic disease and management focuses on symptomatic relief rather than cure. This involves reducing serotonin secretion either medically with somatostatin analogues or in those resistant to medical treatment by debulking hepatic metastases with surgery, radiofrequency ablation or hepatic artery embolization. Symptoms of right heart failure are medically managed with diuretics. Patients with carcinoid heart disease have a 31% survival rate over three years. 3 In appropriate patients, however, valvular surgery improves cardiac symptoms and life-expectancy, and early surgical intervention is recommended, as worsening right heart failure increases risks of surgery. 2
Summary
In summary, we report recurrent carcinoid disease, 19 years after diagnosis of an ileal carcinoid, presenting as dyspnoea on exertion due to carcinoid heart disease picked up on astute echocardiography.
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