6.5 Associated conditions
Carcinoid syndrome
When GEP-NETs metastasise, the most common site for metastatic tumours (‘secondaries’) is the liver. Other areas of spread can include the bones, the lungs and the lymphatic system. Many metastatic NETs can cause symptoms due to over-production of hormones. The most common is carcinoid syndrome, which can occur in approximately 10 per cent of patients and is caused when an excess of hormones such as serotonin, histamine and somatostatin are produced (NORD 2021). The symptoms of carcinoid syndrome vary and can often be highly individual.
Typical symptoms include (NECA 2020a):
- flushing
- diarrhoea
- faecal urgency
- wheezing
- abdominal pain
- pellagra (niacin deficiency). Although rare, pellagra presents as a rash, dark pigmentation on the skin, a swollen mouth and a bright red tongue.
Patients can experience vomiting and diarrhoea, headache, fatigue, depression, disorientation, confusion or memory loss.
Carcinoid crisis
Sometimes patients with functioning NETs may suffer a particularly severe episode of carcinoid syndrome triggered by stressors, general anaesthetic or treatments. Early recognition of a carcinoid crisis enables preventative measures. Symptoms include (NECA 2020a):
- intense flushing
- diarrhoea
- abdominal pain
- wheezing
- palpitations
- low or high blood pressure
- altered mental state and, in extreme cases, coma.
Without treatment, the complications can be life-threatening, but if the patient is having any procedures the NET specialist should ensure the patient is comprehensively monitored and may give an infusion of an SSA (octreotide) as a preventative measure as per institutions policy.
NeuroEndocrine Cancer Australia provides a fact sheet named Carcinoid Crisis and Anaesthesia , and a wallet card for patients, which gives advice on treatment in the event of carcinoid crisis.
Carcinoid heart disease
Up to 20 per cent of patients with carcinoid syndrome present with carcinoid heart disease and, without treatment, can develop right heart failure (NECA 2020b). With SSAs, the progression of carcinoid heart disease is significantly slowed and other symptoms of heart failure may be managed with diuretics. Some patients with carcinoid heart disease may be suitable for cardiac surgery to replace the leaking valves (NECA 2020b). ECG and chest x-ray may provide clues to the diagnosis of carcinoid heart disease, but the most sensitive test is echocardiography of the heart. Echocardiography should be performed regularly to monitor the function of the heart in patients with functional neuroendocrine cancers (NECA 2020b). Urinary 5HIAA is a useful companion biomarker that measures serotonin excretion and also ProBNP (Grozinsky-Glasberg et al. 2015). While early valvular replacement can be complex, this should be managed in a specialist centre with experience in managing carcinoid valvular disease.