Carcinoid Syndrome

Introduction

Carcinoid syndrome is a complication of neuroendocrine tumours which mostly occur in some parts of the gut or in the lungs. These cancers can secrete substances like serotonin and histamine, causing a constellation of symptoms that I remember with the rhyme squeeze, wheeze, flush and faeces. This reminds me that the syndrome often causes issues with our squeezing heart, it can present with a persistent respiratory wheeze as well as skin flushing and diarrhoea.

Neuroendocrine tumours come from cells that normally function as a part of both the nervous and endocrine system. They respond to signalling neurons by releasing things like serotonin in the blood.

As most of these tumours occur in the gut, the secretions usually enter the portal venous system. This is important because they would typically get metabolised by the liver. Here serotonin gets converted into the inactivated version, 5-hydroxyindoleacetic acid or 5HIAA. This is then excreted in the urine just so you can conveniently send it to a lab as a quick way to investigate carcinoid syndrome.

To investigate for carcinoid syndrome, think about bedside tests, bloods, and imaging. At the bedside, a urinary 5-HIAA can be performed. This is usually as a 24-hour collection and would be high.

In reality, blood tests are often unhelpful. For example, serotonin concentrations are not recommended routinely as false positives are frequent. However, UECs and CMPs are great to screen for electrolytes imbalances from the diarrhoea.

A number of imaging tests are available to help you detect for metastatic lesions. In particular, somatostatin receptor scintigraphy is a great investigation. Somatostatin is an inhibitory hormone that binds to neuroendocrine tumours, telling them to switch off production. This is great because it helps us identify the location of tumours and it gives us a clever way to treat the syndrome.

Firstly, if the cancer is surgically operable, then you can just cut it out with curative intent. However, neuroendocrine tumours are mostly metastatic which means this is often not an option.

Symptomatic management can be achieved with the drug octreotide, which is a somatostatin analogue. Similarly, interferon alpha is another drug that not only decreases symptoms but also has an anti-proliferative effects.

Finally, chemotherapy can help to decrease tumour burden but often this is minimally effective for symptoms.

To rationalise the clinical features in carcinoid syndrome, let’s imagine the neuroendocrine tumour has metastasised somewhere like the liver or maybe it’s just started in the lungs. These secretions wouldn’t get metabolised, meaning they can start to work their bad magic while they are hormonally active.

Now serotonin stimulates intestinal secretion and increases motility, that’s why people get diarrhoea. It also stimulates fibrosis which leads to cardiac valvular issues.

Don’t forget though, neuroendocrine tumours produce other substances like histamine, which causes vasodilation and pruritis. This is why people suffer from facial flushing. Finally, these cancers also often produce prostaglandins which might explain a patient’s wheeze.

My mnemonic to remember all of this, is the carcinoid comic. This stands for Cut, octreotide management, interferon alpha and chemotherapy.