Pathophysiology: PTH-rp

Many carcinomas are believed to cause hypercalcaemia by producing parathyroid hormone-related protein (PTH-rp) or by synthesising and releasing soluble factors that stimulate osteoclastic bone resorption.

Parathyroid hormone-related protein and cytokines appear to stimulate bone resorption [6] by increasing osteoclast formation and inhibiting bone formation. Osteoclasts are specialised bone cells that are responsible for bony destruction that generally results in calcium release from the bone into the blood stream. Thus increased stimulation of osteoclast function may lead to increased serum calcium concentrations. In addition to increasing osteoclast activity, PTH-rp increases calcium concentrations by enhancing renal tubular calcium reabsorption. It has been suggested that 1,25-dihydroxyvitamin D3 contributes to hypercalcaemia by increasing intestinal absorption of calcium.

Hypercalcemia also occurs due to ectopic production of PTH and PTH produced by Parathyroid carcinoma and due to Paraprotein binding 2