Question #309
An apparently healthy woman is noted to have a low serum calcium and a low phosphate. This is consistent with:
Parathyroid hormone (PTH) and 1,25dihydroxycholecalciferol (1,25dihydroxy-vitaminD) both have key roles in calcium homeostasis. PTH acts both on bone and on the kidney. Its actions on bone include osteoclast activation, ultimately resulting in calcium resorption: severe PTH excess in the setting of renal failure may result in profound renal bone disease (osteitis fibrosa cystic). Its predominate action on the kidney is to increase calcium reabsorption in the distal convoluted tubule and collecting duct. While PTH does, to an extent, promote phosphate reabsorption in the kidney, this is not an important effect. Hypoparathyroidism is therefore with a low calcium but a near-normal phosphate.
1,25dihydroxycholecalciferol exerts its effects on bone, synergistically with PTH, on the gut, increasing calcium and phosphase absorption, and on the kidney, increasing calcium and phosphate reabsorption. 1alpha-hydroxylation of vitamin D, the first step in its activation, requires UVB radiation, i.e. sunlight. Deficiency is common in the elderly, may receive little sun exposure, and in those who cover their skin. Deficiency results in combined hypocalcaemia and hypophosphataemia. In children it results in rickets, in adults in osteomalacia.
Hypothyroidism is not associated with altered calcium or phosphate homeostasis, other than when the parathyroid glands are damaged in surgery to correct hyperthyroidism.
Calcitonin, secreted by parafollicular C cells in the thyroid and which acts to lower serum calcium, does not play a particular important role in calcium or phosphate homeostasis in adult humans. Deficiency occurring post-thyroidectomy has been shown to impair recovery for experimentally-induced hypercalcaemia, however.
Breast and other cancers may be associated with hypercalcaemia, both as a result of bone destruction by metastases and are a result of secretion of PTH-related peptide by the tumour. Cancers may also be associated with hyperphosphataemia, a marker of increased cell turn over.