What initial investigations should I perform for a patient suspected of having a neuroendocrine tumour?

For a patient suspected of having a neuroendocrine tumour (NET), the initial investigations should include a comprehensive clinical assessment and targeted biochemical and imaging tests to identify the tumour and guide further management. Initial clinical evaluation involves a detailed history and physical examination, including assessment of symptoms such as weight loss, abdominal pain, diarrhoea, or new-onset diabetes, which may suggest pancreatic or gastrointestinal NETs. Basic blood tests should include full blood count, liver function tests, renal function, calcium, and lactate dehydrogenase to assess general health and organ function. Specific tumour markers relevant to NETs include chromogranin A and 5-hydroxyindoleacetic acid (5-HIAA) in urine, although these are not routinely recommended in the initial phase unless clinical suspicion is high or symptoms suggest carcinoid syndrome. Imaging should start with cross-sectional imaging such as a contrast-enhanced computed tomography (CT) scan of the chest, abdomen, and pelvis to localise the primary tumour and detect metastases. If CT is inconclusive or further characterisation is needed, magnetic resonance imaging (MRI) or somatostatin receptor-based imaging (e.g., 68Ga-DOTATATE PET-CT) may be considered, especially for well-differentiated NETs. Histological confirmation via biopsy with immunohistochemistry is essential to confirm diagnosis and differentiate NETs from other malignancies. Endoscopic ultrasound (EUS) with fine-needle aspiration may be particularly useful for pancreatic NETs. These investigations align with the UK guidelines for metastatic malignant disease of unknown primary origin, which recommend symptom-directed imaging and biopsy with immunohistochemistry, and with literature emphasizing the role of biochemical markers and advanced imaging techniques in NET diagnosis Metz & Jensen 2008Elkelany et al. 2023 NICE CG104 Metz & Jensen 2008 Elkelany et al. 2023.