Small cell lung cancer and its paraneoplastic syndromes
Small cell lung cancer classically causes SIADH (syndrome of inappropriate antidiuretic hormone secretion), where excess hormone makes the kidneys retain water and the sodium level falls.
Remember
In a smoker with a lung mass, a low sodium with inappropriately concentrated urine should make you think of small cell lung cancer, because its classic effect is SIADH. A raised calcium makes squamous cell carcinoma (a non-small cell type) the one to think of instead.
Memory aid
small cell holds on to water, so think SIADH, while squamous raises calcium and adenocarcinoma gets clubbed fingers
It pairs each lung cancer type with its classic paraneoplastic effect: water retention with SIADH, a raised calcium, or clubbed fingers.
A paraneoplastic syndrome is an effect of a cancer that comes from substances the tumour makes, such as hormones or antibodies that attack normal tissue, rather than from the size of the tumour or its spread. Small cell lung cancer is a neuroendocrine tumour, meaning that its cells are hormone-producing and nerve-like, so it is especially prone to such effects.
In small cell lung cancer the classic case is ectopic ADH, which means the hormone is made at an unusual site. ADH (antidiuretic hormone) normally comes from the posterior pituitary gland and makes the kidneys hold on to water. Too much of it causes SIADH. The kidneys keep too much water, so the blood becomes dilute and the sodium level falls (dilutional hyponatraemia, meaning a low sodium level that is a dilution effect), yet the urine stays inappropriately concentrated. Brain cells swell in dilute blood, which gives headache, nausea and confusion, and in severe cases seizures.
The tumour is typically central (near the main airways), grows rapidly and spreads early: about 70 to 80% of patients already have metastatic disease (spread of the cancer) at diagnosis. It almost always occurs in smokers.
Other small cell effects are ectopic ACTH, causing increased release of cortisol and so Cushing's syndrome (excess cortisol), and Lambert-Eaton syndrome, an autoimmune condition of the neuromuscular junction (where nerve meets muscle) causing proximal muscle weakness. Squamous cell carcinoma, a non-small cell type, can release parathyroid hormone related peptide (PTHrP), which mimics parathyroid hormone and raises the blood calcium (hypercalcaemia). Adenocarcinoma, another non-small cell type, goes with hypertrophic pulmonary osteoarthropathy, a triad of finger clubbing, new bone formation along the long bones and painful large joints.
Key facts
- Classic hormone
- ectopic ADH, causing SIADH, is the classic paraneoplastic effect of small cell lung cancer.
- SIADH picture
- a low sodium with low plasma osmolality (dilute blood), urine that is inappropriately concentrated, normal fluid status and no diuretic to explain it.
- Other small cell syndromes
- ectopic ACTH causing Cushing's syndrome, and Lambert-Eaton syndrome.
- Squamous cell carcinoma
- can release PTHrP, which raises the blood calcium.
- Adenocarcinoma
- hypertrophic pulmonary osteoarthropathy, with clubbing.
- Behaviour
- rapid growth and early metastasis, with about 70 to 80% of patients already having metastatic disease at diagnosis.
- Smoking
- small cell lung cancer almost always occurs in smokers.
Exam traps
- Parathyroid hormone related peptide (PTHrP) does not point to small cell lung cancer, because it is the classic product of squamous cell lung cancer, where it causes a high calcium.
- Hypertrophic pulmonary osteoarthropathy is not the classic small cell syndrome, because it is most common with non-small cell lung cancer and is often linked to adenocarcinoma.
- Myasthenia gravis (an autoimmune weakness disorder) is not a classic small cell paraneoplastic syndrome; the related neuromuscular junction disorder that is, is Lambert-Eaton syndrome.
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