Local effects of tumours

The local growth of a tumour can cause a wide range of abnormalities in commonly requested biochemical tests. This may be a consequence of obstruction of blood vessels or ducts, e.g. the blockage of bile ducts by carcinoma of head of pancreas causes elevated serum alkaline phosphatase and sometimes jaundice. The symptoms that result from such local effects may be the first sign to the patient that something is wrong, but there may be no initial suspicion that there is an underlying malignancy.

The liver is often the site of metastatic spread of a tumour. An isolated increase in the serum alkaline phosphatase or γGT is a common finding when this occurs. Even with significant liver involvement, there may be no biochemical abnormalities. Modest increases in the aminotransferases, ALT and AST, are observed if the rate of cell destruction is high.

Metastatic spread of a tumour to an important site may precipitate complete system failure. For example, destruction of the adrenal cortex by tumour causes impaired aldosterone and cortisol secretion, with potentially fatal consequences.

Rapid tumour growth gives rise to abnormal biochemistry. Leukaemia and lymphoma are often associated with elevated serum urate concentrations due to the rapid cell turnover. Serum lactate dehydrogenase is often elevated in these patients, reflecting the high concentration of the enzyme in the tumour and the cellular turnover, and may be a sign of intravascular haemolysis. Large tumours may not have an extensive blood supply and the tumour cells meet their energy needs via anaerobic glycolysis. This may result in the generation of a lactic acidosis.

Renal failure may occur in patients with malignancy for the following reasons:

Cancer cachexia

Cancer cachexia describes the characteristic wasting often seen in cancer patients. The features include anorexia, lethargy, weight loss, muscle weakness, anaemia and pyrexia. The development of cancer cachexia is due to many factors and is incompletely understood. Certainly, there is an imbalance between dietary calorie intake and body energy requirements. This results from a combination of factors:

Tumour spread may cause infection, dysphagia, persistent vomiting and diarrhoea, all of which may contribute to the overall picture seen in cancer cachexia. The observation that small tumours can have a profound effect on host metabolism suggests that cancer cells secrete or cause the release of humoral agents that mediate the metabolic changes of cancer cachexia. Some of these, such as tumour necrosis factor, have been identified. This cytokine is secreted by activated macrophages and acts on a variety of tissues including muscle, adipose tissue and liver.

Ectopic hormones

It is a characteristic feature of some cancers that they secrete hormones, even though the tumour has not arisen from an endocrine organ. Referred to as ectopic hormone production, hormone secretion by tumours has frequently been invoked but rarely proven (Fig 69.2). Small cell carcinomas are the most aggressive of the lung cancers and are the most likely to be associated with ectopic hormone production. Ectopic ACTH secretion causing Cushing’s syndrome is the most common. However, the classic clinical features of Cushing’s syndrome are not usually apparent in the rapidly progressing ectopic ACTH disorder. Biochemical features include hypokalaemia and metabolic alkalosis and these may be the sole indicators of the problem.

Not infrequently, patients with malignancy develop the syndrome of inappropriate antidiuresis (SIAD). Water is retained and patients present with hyponatraemia. This is probably the commonest biochemical abnormality seen in patients with cancer and is almost invariably due to pituitary AVP secretion in response to non-osmotic stimuli. SIAD is often, incorrectly, attributed to ectopic AVP secretion, which is in fact very rare.

Some cancers may cause hypercalcaemia. In many cases this is due to the secretion of parathyroid hormone related protein, PTHrP, so called because of its relationship with PTH both in its structure and function.

Consequences of cancer treatment

Anti-tumour therapy can have serious effects. Gonadal failure arising from radiotherapy or chemotherapy is frequently encountered, as is osteopenia. Hypomagnesaemia and hypokalaemia may be a consequence of the use of the cytotoxic drug cisplatin. Patients treated with methotrexate may become folate deficient.

Hyperuricaemia is a consequence of the massive cell death that occurs in the treatment of some tumours with cytotoxic drugs, particularly lymphomas and some leukaemias, and is known as tumour lysis syndrome.