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Could His Anxiety Be Carcinoid Syndrome?

Carlos was a 62 year old man who had a long history of treated anxiety. He had been taking fluoxetine 20mg daily for years and although he had occasional relapses, he could generally cope with them. In the last six months, however, he had noted his irritable bowel syndrome had worsened and the pattern was changing. He now had diarrhoea most days first thing in the morning, but now without alternating constipation. His last colonoscopy was normal two years ago. Carlos had also noted facial flushing that was worse with stress, if there were a heat source nearby, and with exercise. He did not suffer any skin conditions normally. He was a lifelong non-smoker and had no history of cardiorespiratory disease but now, intermittently, he felt short of breath with exercise. His wife felt he had been generally a lot more stressed in the last few months over work and that this was likely to be the cause, but Carlos said he felt stressed because something was wrong. Who was correct?

The GP took a further history. There was no weight loss or change in appetite. Carlos had for a long time suffered what had been diagnosed as psychological impotence but took no medication for this. His physical examination was normal but Carlos appeared clearly anxious. His blood pressure was 155/94 mmHg and his pulse rate was 78 beats per minute and regular. In particular, there was no periorbital oedema, facial telangectasia or flushing.

Malignant carcinoid syndrome is the triad of facial flushing, significant diarrhoea (many times daily despite fasting) and bronchospasm (this occurs in relation to the flushing). Other symptoms include fatigue, palpitation, hypotension and aesthenia, and rarely irritability, myopathy and arthralgia. Gastrointestinal bleeding is not a typical association with carcinoid tumours but pain, cramping and occasionally bowel obstruction can occur. The syndrome is rare, occurring in approximately one to two patients in one hundred thousand (although many more have an asymptomatic carcinoid tumour). The syndrome is due to tumour tachykinins from the metastases (with the exception of ovarian carcinoid, as this can produce the syndrome without having metastasised).

Less than 10% of patients who have a carcinoid tumour develop malignant carcinoid syndrome. The prognosis depends on the size of the tumour and whether it has metastasised; this is much more common in tumours over 2cm in size and much less common in tumours under 1cm in size. Mortality is linked to cardiac complications, most commonly right heart failure from triscuspid stenosis and endocardial thickening affecting the chordae, papillary muscles, valves and ventricular function due to the serotonin output. Liver disease from the tumour burden and complications related to the syndrome are other causes of demise.

This tumour is of neuroendocrine origin and produces vasoactive hormones, such as 5-hydroxytryptamine and histamine. It is most common in the sixth and seventh decade of life. One third of carcinoid tumours are multiple and one third occur in the small bowel (90% from the distal ileum and appendix). The other two commonest places for these tumours to occur are the bronchi and the rectum. Rarely, they are found in the pancreas, gallbladder, liver, larynx, testes and ovaries; tumours occurring outside the small bowel carry a poorer prognosis due to increased risk of metastasis.

Lung carcinoids may secrete adrenocorticotropic hormone, histamine, gastrin and serotonin. Gastric carcinoids are associated with hypochlorhydria and pernicious anaemia (50% of cases have this). Colonic carcinoid tumours tend to be associated with weight loss and anorexia and are often larger and multiple at diagnosis. One third of carcinoid tumours are associated with another malignancy elsewhere, and one third of these tumours will metastasise, usually to local nodes, the liver, and then to skin and essentially any organ.

The differential diagnosis of malignant carcinoid syndrome includes anaphylaxis, urticaria, anxiety, niacin deficiency (pellagra), angioedema, coeliac disease and irritable bowel syndrome. Investigation involves the identification of vasoactive hormones in blood and urine (a 24-hour urinary collection of 5-H1AA). Scinitgraphy with DTPA is also often suggested. For interest, a complete list of the huge number of hormonally active substances produced by carcinoid tumours may be found at the reference below. Imaging (multiphasic CT or MRI of the chest, abdomen and pelvis) is suggested to identify the origin of the tumour and colonoscopy and upper endoscopy is usual. A cardiac echo is also indicated if the diagnosis is confirmed.

Surgery is the best management when possible and octreotide is the usual medical management. However, antihistamines (cyproheptadine, ranitidine), clonidine, serotonin antagonists and colonic antispasmodics may also be symptomatically useful. High dose steroids have been used for severe malignant carcinoid syndrome. Radiotherapy is less successful with these tumours and conventional chemotherapy does not improve survival. High protein, high calorie diets are recommended as patients have a tendency to weight loss from malabsoption; stress, alcohol and adrenaline-like medications should be avoided, and exercise should be restricted to mild activities in patients with malignant carcinoid syndrome.

As it turned out, after a full investigation, Carlos did not have malignant carcinoid syndrome. It was, however, an important differential diagnosis as the signs and symptoms often begin gradually and insidiously.


1. Santacroce, L. Malignant Carcinoid Syndrome. Medscape, March 2016.