TABLE 2.
Paraneoplastic syndromes with their associated antibodies
| Paraneoplastic syndrome | System | Incidence | Causative protein or antibody | Clinical features | Diagnosis |
|---|---|---|---|---|---|
| Hypercalcaemia | Endocrine | 10% | PTHrP binds to PTH receptors in the bone, kidneys and influences Ca–phosphorous regulation | Polydipsia, polyuria, hypertonia, renal failure, vomiting, altered sensorium | Elevated Ca Elevated PTHrP Decreased PTH |
| SIADH | Endocrine | 10–45% | Ectopic ADH secretion by cancer cells which inhibits free water excretion in the distal tubule of the kidney | Nausea, vomiting, cramps, depressed mood, irritability, personality changes (aggression), seizures, stupor or coma | Hyponatraemia; rule out other causes such as drug-induced, excess fluids, low intake of sodium due to cachexia |
| Ectopic Cushing syndrome | Endocrine | 5% | Cancer cells express POMC precursor gene which is translated into a prohormone later cleaved into ACTH | In carcinoids: typical cushingoid features like centripetal fat distribution, proximal myopathy, hypertension In SCLC: less cushingoid features, hyperglycaemia, weight gain due to water retention |
High serum ACTH, hypercortisolism, i.e. increased 24 UFC or salivary cortisol; 1 mg dexamethasone suppression test |
| Carcinoid syndrome | Endocrine | 1–5% | Serotonin release by cancer cells | Acute: prolonged flushing in the upper torso, bronchospasm, diarrhoea Chronic: fibrosis of right heart valves, retroperitoneum Rare: hypotension and cardiac arrest |
24 h urine 5-HIAA Radiolabelled octreotide |
| Lambert–Eaton myasthenic syndrome | Neurological | 3% | Anti-VGCC | Proximal muscle weakness, typically improving with repetitive action | EMG, anti-VGCC antibodies |
| Paraneoplastic cerebellar degeneration | Neurological | <1% | Anti-Yo, anti-Hu, anti-VGCC, anti-Tr, anti-Ri | Rapid onset of truncal and appendicular ataxia, imbalance, dizziness, nausea, diplopia, dysphagia, nystagmus | Paraneoplastic antibody assay, MRI, rapid onset of ataxia |
| Limbic encephalitis | Neurological | <1% | Anti-Hu, anti-Ma2, anti-Ri | Subacute onset of mental status changes, memory deficits, behavioural changes, emotional lability, insomnia, seizures | Clinical symptoms, EEG, MRI, anti-Hu antibodies |
| Paraneoplastic opsoclonus- myoclonus | Neurological | <1% | Anti-Hu, anti-Ri, anti-Ma2, anti-amphiphysin | Large amplitude ocular saccades and other abnormal eye movements alone or in combination with myoclonus; hypotonia, irritability, ataxia and encephalopathy | Physical examination for abnormal eye movement, MRI, anti-Hu antibodies |
| Autonomic neuropathy | Neurological | <1% | Anti-Hu, anti-gAChR | Orthostatic hypotension, arrhythmias, impotence, intestinal pseudo-obstruction | Clinical symptoms, anti-Hu antibodies |
| Hypercoagulability | Vascular | <1% | Unknown | Trousseau syndrome, deep venous thrombosis, disseminated intravascular coagulopathy | Clinical symptoms, coagulation panel, d- dimers |
PTH: parathyroid hormone; PTHrP:- parathyroid hormone-related protein; SIADH: syndrome of inappropriate antidiuretic hormone; ADH: antidiuretic hormone; Ca: calcium; ACTH: adrenocorticotropic hormone; UFC: urine free cortisol; 5-HIAA: 5-hydroxyindoleacetic acid; EMG: electromyography; VGCC: voltage gated calcium channel; EEG: electroencephalogram; MRI: magnetic resonance imaging.