Pathogenesis of hypercalcaemia of malignancy.
The hypercalcaemia of malignancy is multi-factorial, even within individual tumours. In most cases, hypercalcaemia is due to a combination of increased bone resorption associated with decreased renal capacity to excrete the increased extracellular fluid calcium. In solid tumours such as carcinoma of the lung, tumour-derived growth factors are probably primarily responsible for the increased bone resorption, and a separate family of factors which interact with some parathyroid hormone (PTH) receptors cause increased renal tubular calcium reabsorption. PTH production by non-parathyroid tumours rarely if ever occurs. In contrast, haematological malignancies such as myeloma and T-cell lymphomas produce locally acting bone resorbing lymphokines in excessive amounts. Some T-cell lymphomas in addition have the capacity to metabolize 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D. In myeloma, impaired glomerular filtration frequently contributes to the pathogenesis of hypercalcaemia by impairing renal compensatory mechanisms for maintaining normal serum calcium concentrations in the presence of increased bone resorption.
D001862:Bone Resorption; D001943:Breast Neoplasms / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D017977:Deltaretrovirus; D005110:Extracellular Space / Q000378:metabolism; D006133:Growth Substances / Q000096:biosynthesis; D006801:Humans; D006934:Hypercalcemia / Q000209:etiology* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism; D008223:Lymphoma / Q000378:metabolism; D009101:Multiple Myeloma / Q000378:metabolism; D009369:Neoplasms / Q000150:complications* / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism; D010452:Peptide Biosynthesis; D011956:Receptors, Cell Surface / Q000378:metabolism; D018016:Receptors, Parathyroid Hormone; D015291:Transforming Growth Factors
D006133:Growth Substances; D010281:Parathyroid Hormone; D011956:Receptors, Cell Surface; D018016:Receptors, Parathyroid Hormone; D015291:Transforming Growth Factors; D002118:Calcium