Neuroendocrine Tumours
Developments in Digestive Tract Neuroendocrine Tumours and Pheochromocytomas/Paragangliomas – A Narrative Review
Ioannis Ilias1 and Karel Pacak2
1. Endocrinologist, Department of Endocrinology, E Venizelou Hospital, Athens; 2. Chief and Senior Investigator, Section on Medical Neuroendocrinology, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health
Abstract
Digestive neuroendocrine tumours (carcinoids) derive from serotonin-producing enterochromaffin cells. Biochemical screening (and follow-up) is performed with measurements of 5-hydroxyindoloacetic acid in urine. Other markers are also useful. Most digestive neuroendocrine tumours are better localised with functional imaging, i.e. nuclear medicine, compared with other modalities. The treatment of choice is surgical; non-resectable tumours are treated with somatostatin analogues (unlabelled and for more advanced disease radiolabelled) or chemotherapy. Most pheochromocytomas/paragangliomas are sporadic, however, and genetically caused tumours are much more common than previously thought. Biochemical proof of disease is best carried out with measurement of plasma metadrenaline. Imaging with computed tomography or magnetic resonance imaging (MRI) should be followed by functional imaging. Chromaffin tumour-specific methods are preferred. 18F-fluoro-deoxyglucose positron emission tomography (18F-DOPA PET) should be used in patients with succinate-dehydrogenase-B-related metastatic pheochromocytoma/paraganglioma. 18F-DOPA PET may become a modality of choice for the localisation of head and neck paragangliomas. If possible, treatment is surgical. For non-operable disease, other options are available and new drugs are under investigation or in clinical trials.
Keywords
Digestive neuroendocrine tumours, pheochromocytomas, paragangliomas, metadrenaline, radionuclide imaging, succinate dehydrogenase complex
Disclosure: The authors have no conflicts of interests to declare. Acknowledgement: The writing of this article was supported by the Intramural Research Program of The Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health (Bethesda, Maryland, US). Received: 22 July 2010 Accepted: 15 September 2010 Citation: European Endocrinology, 2010;6(2):59–64 Correspondence: Ioannis Ilias, Department of Endocrinology, E Venizelou Hospital, 2 E Venizelou Sq, Athens GR-11521, Greece. E:
iiliasmd@yahoo.com
Digestive Neuroendocrine Tumours Digestive neuroendocrine tumours (carcinoids) derive from serotonin- producing enterochromaffin cells. The digestive neuroendocrine tumours are classified as:
• •
foregut – originating from the oesophagus to the pancreas;
midgut – ‘classic’; presenting with the carcinoid syndrome that includes flushing, diarrhoea and hypotension. They originate from the jejunum to the right colon and gonads; or
• hindgut – ‘silent’; originating from the transverse colon to the rectum.
More than half of digestive neuroendocrine tumours originate in the gastrointestinal tract (with half of these in the small intestine) and the remaining from the lungs/bronchi. The overall incidence of digestive neuroendocrine tumours is estimated to be one to five per million population.1
Patients with midgut digestive neuroendocrine tumours may complain of vague abdominal symptoms for a long time (approximately nine years) before classic symptoms and signs, such as flushing and excess gastrointestinal motility are observed.2,3
At
this time, the disease has metastasised in 90% of symptomatic patients.2,3
More than half of patients with digestive neuroendocrine tumours – via mechanisms that are not clearly understood – suffer © TOUCH BRIEFINGS 2010
from irreversible carcinoid heart disease. The endocardium shows fibrous thickening and the tricuspid and pulmonary valves are fixated.2,4
Genetics
Ten per cent of individuals with multiple endocrine neoplasia (MEN) type 1 have digestive neuroendocrine tumours. MEN1 is an autosomal dominant disorder caused by deletion of the MEN1 suppressor gene on chromosome 11q13. Forty to 80% of patients with sporadic digestive neuroendocrine tumours also show loss of heterozygozity in chromosome 11 or deletion of the MEN1 gene.2,5
Pulmonary
neuroendocrine tumours are associated with mutations in the p53 suppressor gene and variability in B-cell lymphoma 2 (Bcl-2) expression.2
Studies of polymorphisms of the nuclear factor-kappaB
(NFκB) transcription factor tentatively point to differences in the genetics of digestive neuroendocrine tumours vis-à-vis pancreatic neuroendocrine tumours.6
Biochemical Diagnosis
Digestive neuroendocrine tumours in the fore- and midgut metabolise tryptophan to 5-hydroxytryptophan and synthesise and secrete serotonin. The measurement of the latter’s major metabolite 5-hydroxyindoloacetic acid (5-HIAA) in urine is proposed by most experts as the biochemical screening (and follow-up) test of choice.7,8
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