| Ch 16 | Page 10 / 16 | |
| Cancer emergencies |
Metabolic emergencies (1) | |
Hypercalcaemia is a common manifestation among cancer sufferers: 20 – 40 % of multiple myeloma, 35% of lung cancers, 24% of kidney cancers, 8-10% of breast cancer. Hypercalcaemia generally underlines the poor prognosis of cancer, although new therapies may offer longer patient survival.
There are two different circumstances, whether osteolytic lesions are present or not.
If osteolytic lesions are present, then hypercalcaemia is generally a late phenomenon underlining poor prognosis. Hypercalcaemia induces symptoms that should be corrected with efficient palliative care.
Many hypercalcaemia appear without any osteolytic lesions and are therefore true paraneoplastic syndromes possibly due to several mechanisms:
- Production of proteins which bind to the parathormone receptor (PTH-like): in the tumour DNA, a gene expresses a polypeptide (PTH-RP or parathormone related protein) with 70% homology with normal parathormone. This gene is normally expressed in mammary tissue during lactation.
- Myeloma tumour cells produce a factor that stimulates osteoclasts (or OAF: Osteoclast Activating factor) which can be produced by in vitro stimulated normal leukocytes. OAF is one member of a larger family of factors called lymphokines, with lymphotoxine (produced by activated lymphocytes) and TNF (tumor necrosis factor or cachectine) produced by normal monocytes. Both factors stimulate osteoclasts.
- Several lymphoma, bone tumours or sarcoma can induce hypercalcaemia by transforming normal 25-hydroxy-vitamine D into 1,25 – dydroxy- vitamine D (the final active metabolite of vitamine D).
There is no clear relationship between the presence of bone metastases and the elevation of serum calcium: some diffuse metastases, with major mechanical complications, never produce hypercalcaemia, whereas some very evolutive hypercalcaemia, difficult to reduce, have normal imaging even with gammagraphy and RMI.
The main symptoms of hypercalcaemia are:
- Anorexia, thirst, constipation or even occlusion,
- Consciousness disorders: fatigue, somnolence, lethargy, coma
- More or less intense dehydration, initially extra-cellular then intra-cellular.
Diagnosis is made by calcaemic dosage which should systematically be requested in the case of doubt.
Untreated hypercalcaemia leads to severe dehydration and possibly to patient death by cardiac rhythm disorders.
Malignant hypercalcaemia is easy to distinguish from other forms of hypercalcaemia: generally blood phosphorus is normal or elevated (as opposed to hyperparathyroidism).
Several treatment modalities have been proposed depending on the clinical severity of hypercalcaemia.
However, diphosphonates (in particular intravenous forms) have totally modified such modalities allowing ambulatory treatment over several weeks, with prolonged survival and good quality of life.
The only major point to ensure is correct patient rehydration, if necessary intravenously. Corticosteroids are still useful if hypercalcaemia is very high.
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