Cancer can manifest as signs and symptoms that may not be directly related to the cancer itself. These are known collectively as paraneoplastic syndromes and they exert a wide range of effects via depletion of normal factors, production of ectopic substances, or a host immunological response to the tumour.
Ectopic hormone production
In some cases, the first presentation of cancer is with a metabolic abnormality due to ectopic production of hormones by tumour cells, including insulin, ACTH, ADH, FGF23, erythropoietin, PTHrP and gonadotrophins (Table 11.1). If the cancer is successfully treated, the ectopic production is stopped and the metabolic abnormality resolves.
Cushing’s syndrome can result from a pituitary adenoma (Cushing’s disease), exogenous steroids, or an adrenal adenoma, but 20% of cases result from ectopic ACTH production. Patients can often present with the clinical features of hypercortisolism and hypokalaemic metabolic alkalosis with muscle weakness, hypertension, oedema, confusion, glucose intolerance and weight gain. Diagnosis can be confirmed by demonstrating a high 24-hour urinary free cortisol, high serum ACTH (>200 pg/mL) and failure to suppress ACTH production following a high-dose dexamethasone suppression test. Most cases (>50%) are associated with small cell lung cancer and neuroendocrine tumours (15%), such as phaeochromocytoma, carcinoid tumours, neuroblastoma and medullary cell carcinoma of the thyroid.
Carcinoid syndrome results from the production of serotonin, typically from the enterochromaffin cells in the gastrointestinal tract, pancreas and lungs. The serotonin and kinins are normally secreted into the portal circulation and undergo first-pass metabolism in the liver, and therefore none reaches the systemic circulation to cause symptoms. However, if the primary site is outside the portal circulation, or the patient has developed metastasis to the liver, then the release will be directly into the systemic circulation. This produces symptoms of vasomotor flushing, diarrhoea, wheezing, fever and abdominal pain. Chronic complications include tricuspid incompetence, cirrhosis, arthropathy and pellagra due to tryptophan deficiency. Diagnosis is by collection of 24-hour urine samples for 5-hydroxyindoleacetic acid (5-HIAA), which is a metabolite of 5-HT.
Neurological manifestations
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