5. carcinoid tumour biochemical and radiological testing
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Carcinoid TumourBiochemical and Radiological
Testing
Gillian Harris 4th year MBBS
Carcinoid Tumour-background
• Rare, slow growing• Derived from resident neuroendocrine cells• Most often found in GIT (2/3) and lung • Secrete various substances including
-Serotonin -Histamine-Bradykinin -Prostaglandins-Kallikrein -Adrenocorticotropic
hormone-Neuropeptide K -Gastrin-Neurokinins A & B -Calcitonin-Substance P -Growth hormone
• Carcinoid syndrome
Biochemical Markers• 5-hydroxy-indole-acetic acid (5-HIAA)
– End product of serotonin metabolism– Measured in 24 hour urinary collection– Sensitivity 75% Specificity 100%
• Chromogranin A (CgA)– In wall of synaptic vesicles that store
serotonin and glucagons– Levels correlate with tumour bulk– Elevated in 85-100% pts with carcinoid
tumour– Sensitivity 67.9% Specificity 85.7%
5-hydroxy-indole-acetic acid (5-HIAA)
• End product of serotonin metabolism
• Normal rate of excretion 2-8mg/day
• Sensitivity of 73%
• Specificity of 100%
Serotonin overproduction
• Increased values of Urinary 5-HIAA secretion occur with:– Malabsorption syndromes – Ingestion of tryptophan-rich foods (eg
bananas and avocadoes)– Certain drugs
Other methods for measuring serotonin overproduction
• Urinary Serotonin
• Platelet concentration of serotonin
Chromogranin A(CgA)
• Found in the wall of secretory vesicles of neuroendocrine cells
• Widely distributed throughout the neuroendocrine system
• Immunohistochemical staining can detect the presence of CgA in the circulation
• CgA is elevated in 85-100% pts with carcinoid tumour
• Specificity 85.7%
• Sensitivity 67.9%
for neuroendocrine tumours
Other causes of increased serum CgA
• Renal impairment
• Liver Failure
• Atrophic Gastritis
• Irritable bowel disease
• Proton pump inhibitors
• Physical Stress
Diagnostic Imaging• Neuroendocrine tumours express:
– Neuroamine uptake mechanisms– Specific receptors (eg. Somatostatin receptors)
• Radiolabelled amines/peptides bound to suitable ligands target specific cells
• Gamma camera visualises uptake
• Improved localisation with simultaneous conventional imaging (eg. CT/MRI)
111In-Pentetreotide Scintigraphy
• 111In-labelled somatostatin analogue• Concentrates in neuroendocrine and some non-
neuroendocrine tumours containing somatostatin receptor subtypes 2 and 5
• 80-90% sensitivity for carcinoid tumours (10)• Identifies lesions not visualised on conventional
imaging– 1/3-2/3 patients had additional localisations– 65 extra lesions found per 100 patients
(11) Van der Lely; De Herder. Carcinoid Syndrome: diagnosis and medical management Arq Bras Endocrinol Metab. 2005: 49:5
Meta-iodobenzylguanidine (MIBG) Scintigraphy
• Guanidine derivative• Utilises Type 1 amine uptake mechanism of cell• Found in carcinoid and other neuroendocrine
tumours • Uses 123I- or 131I-labelled MIBG• 123I-labelled MIBG has a superior image quality• Useful for tumours which do not have
somatostatin receptors• Select patients for MIBG therapy
Conventional Imaging Modalities
• CT
• MRI
• Transabdominal ultrasound
• Endoscopy
• Endoscopic ultrasound
• Selective mesenteric angiography
Tumour type Imaging (12)
Foregut Chest radiography-occasionally detects lesions
CT/MRI-identification of primary tumour, lymph nodes, facilitates biopsy diagnosis
Octreotide Scintigraphy-negative in 30% but most specific
Midgut Octreotide Scintigraphy-staging and identification of primary lesion. 83% diagnostic accuracy, 100% PPV
Transabdominal Ultrasound-1/3 Small bowel carcinoids, 2/3 liver metastases
CT/MRI-to monitor responsiveness to treatment, only detect 50% primary tumours
Double contrast barium studies-to assess for imminent obstruction
Hindgut Octreotide scintigraphy-highest sensitivity
MIBG-when negative scan
Endoscopic ultrasound-90% accuracy for localisation and staging of colorectal carcinoids
MRI
Positron Emission Tomography (PET)
• Carcinoids are slow growing, well differentiated tumours
• FDG has detection rates 25-73%
• Newer tracers:– 11C-5-HTP– 68Ga coupled to octreotide
• More evidence necessary
Summary
• Biochemical Markers– 5-hydroxy-indole-acetic acid (5-HIAA)– Chromogranin A (CgA)
• Radiological Imaging– 111In-Pentetreotide Scintigraphy– Meta-iodobenzylguanidine (MIBG)
Scintigraphy– Conventional Imaging (CT/MRI/Ultrasound)– PET
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