Paraneoplastic syndromes: the table to know !
- Topic
Some cancers cause symptoms far from the tumour, through hormones they make or antibodies the body makes against them.
Updated 2026-11-01
What it is
Paraneoplastic syndromes are signs and symptoms that cannot be explained by the local growth of the tumour or its metastases. They arise from hormones or cytokines made by the tumour (ectopic ACTH, ADH, PTH-related peptide) or from antibodies against tumour antigens that cross-react with normal tissue, mainly nerves and muscle. They matter because they may be the first sign of a hidden cancer and can themselves be life-threatening.
Key facts
- Small cell lung carcinoma, of neuroendocrine origin, causes the most paraneoplastic syndromes (ACTH, ADH, Lambert–Eaton, anti-Hu encephalomyelitis).
- Hypercalcaemia is the most common paraneoplastic syndrome; PTHrP-mediated hypercalcaemia has low PTH.
- Neurological examples: anti-Yo cerebellar degeneration (ovary, breast) and anti-NMDA receptor encephalitis (ovarian teratoma).
- Carcinoid syndrome is usually a sign of liver metastases from a gut neuroendocrine tumour.
Step by step
- The tumour expresses a protein that its tissue of origin would not normally make in excess.
- Endocrine route: the protein is a hormone (ACTH, ADH, PTHrP, erythropoietin) secreted into the blood.
- It acts on distant target organs, producing a hormonal syndrome without the normal feedback control.
- Immune route: the tumour expresses an antigen shared with neurons or muscle (an onconeural antigen).
- Antibodies and T cells directed at the tumour also attack the normal tissue (synapse, cerebellum, muscle).
- Treating the tumour often improves endocrine syndromes; immune damage to neurons may persist.
Paraneoplastic syndromes to know
| Syndrome | Mechanism | Typical tumours |
|---|---|---|
| Hypercalcaemia | PTH-related peptide (PTHrP); less often calcitriol or bone metastases | Squamous cell lung carcinoma, breast, kidney, head and neck; calcitriol in lymphomas |
| SIADH (hyponatraemia) | Ectopic ADH | Small cell lung carcinoma |
| Cushing syndrome | Ectopic ACTH | Small cell lung carcinoma, carcinoid tumours, pancreatic neuroendocrine tumours |
| Lambert–Eaton myasthenic syndrome | Antibodies against presynaptic voltage-gated calcium channels | Small cell lung carcinoma |
| Myasthenia gravis | Antibodies against the acetylcholine receptor | Thymoma |
| Polycythaemia | Erythropoietin | Renal cell carcinoma, hepatocellular carcinoma, cerebellar haemangioblastoma |
| Hypoglycaemia | Insulin-like growth factor 2 or insulin | Large mesenchymal tumours, hepatocellular carcinoma; insulinoma |
| Migratory thrombophlebitis (Trousseau) | Mucins and tissue factor activate coagulation | Pancreatic and other mucin-producing adenocarcinomas |
| Dermatomyositis and acanthosis nigricans | Immune or growth factor mediated | Ovary, lung, stomach (acanthosis: gastric adenocarcinoma) |
| Hypertrophic osteoarthropathy (clubbing) | Unclear (growth factors, platelets) | Lung carcinoma |
Clinical notes
- An unexplained hypercalcaemia, hyponatraemia, rapid-onset Cushing syndrome or Lambert–Eaton weakness should start a search for cancer.
- Lambert–Eaton weakness improves with repeated effort, unlike myasthenia gravis.
- An unexplained venous thrombosis, especially recurrent or migratory, may precede a pancreatic or other adenocarcinoma.
- Paraneoplastic syndromes can be fatal on their own (severe hypercalcaemia or hyponatraemia).
Test yourself
Think of the answer, then tap the question to see it.
Which paraneoplastic hormone causes hypercalcaemia in squamous cell lung carcinoma, and what happens to PTH?
PTH-related peptide (PTHrP); the patient's own PTH is suppressed (low).
Which lung tumour causes ectopic ACTH, SIADH and Lambert–Eaton syndrome?
Small cell lung carcinoma, a neuroendocrine tumour.
What is the target of the antibodies in Lambert–Eaton syndrome?
Presynaptic voltage-gated calcium channels at the neuromuscular junction, which reduces acetylcholine release.
Which tumours classically cause polycythaemia through erythropoietin?
Renal cell carcinoma, hepatocellular carcinoma and cerebellar haemangioblastoma.
Related
- Local effects of tumours and cancer cachexia
- Tumour markers: serum and tissue, and what each one is for
- Hypercoagulable states: inherited and acquired
- Naming tumours: -oma, carcinoma, sarcoma, and the misleading names
Related conditions
- Paraneoplastic syndromes
- Lung cancer
- Renal cell carcinoma
- Hepatocellular carcinoma
- Hypercalcaemia of malignancy
- Hypercalcaemia
- Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
- Lambert-Eaton myasthenic syndrome
- Cushing syndrome
- Myasthenia gravis
- Inflammatory myopathies (dermatomyositis, polymyositis)
- Acanthosis nigricans
- Hypertrophic osteoarthropathy and digital clubbing
- Carcinoid syndrome
- Pancreatic cancer
Elsewhere in DurgiPedia
- Calcium regulation: PTH, vitamin D and calcitonin
- ADH, thirst and water balance
- Erythropoiesis and erythropoietin
- Actions of cortisol
- Tumor immunology and checkpoint inhibitors
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Small Cell Lung Cancer (StatPearls (NCBI Bookshelf), 2024); Parathyroid hormone-related protein blood test: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Syndrome of inappropriate antidiuretic hormone secretion: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Hypercortisolism (Cushing Syndrome) (StatPearls (NCBI Bookshelf), 2024).
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Representative model, for educational purposes only.