Non-parathyroid hypercalcemia

Abstract

Hypercalcemia is one of the most commonly found disorders in clinical practice. Calcium is involved in countless organic processes, such as the coagulation cascade, enzymatic reactions, and neuromuscular transmission, and it is thus important to maintain its homeostasis. As it is involved in so many vital processes, its concentration in serum is well controlled, presenting minimal variations in normal circumstances. There is around 1-2 kg of calcium in the average adult, of which about 99 % is concentrated in the skeleton. The remainder is situated in intra- and extracellular fluids. The distribution of calcium in the blood occurs in the following manner: around 50 % in diffusible form (ionizable calcium and calcium in the form of complexes with organic anions: bicarbonate, citrate, phosphate, lactate, and sulfate) and the rest, which is nondiffusible, linked to plasmatic proteins. The portion of calcium linked to albumin represents 40 % of the total, at a proportion of 0.8 mg/dl of calcium for every 1 g/dl of albumin (Berne and Levy, Fisiologia 3ed;199:823-41). A decrease in serum levels of albumin thus causes alterations in the concentration of total serum calcium. However, in hypoalbuminemic states, as in critical patients, the corrected calcium has to be calculated, or rather, ionizable calcium measured in such a way as not to be influenced by the albumin levels. On the other hand, dehydration or the movement of fluids out of the vascular system, owing to a tight tourniquet, for example, may produce an increase in albumin levels, causing pseudohypercalcemia. Pseudohypercalcemia can also be found in cases of multiple myeloma, owing to the high-affinity association between calcium and the monoclonal protein of myeloma, giving rise to a marked increase in serum concentrations of calcium (Elizabeth et al. Diagnostic approach to hypercalcemia. http:// www.uptodate.com, 2012). The formula for calculating corrected calcium is corrected calcium = total calcium + (4-albumin) x 0.8. The ionizable portion of calcium is regulated by parathormone (PTH) and vitamin D. It may vary with blood pH, as acidosis increases the concentration of ionizable calcium and reduces alkalosis. A change of 0.1 in serum pH modifies the protein-calcium link by 0.12 mg/dl (Hauache, Braz J Med Biol Res 34(5):577-84, 2000). In adults, around 20-30 % of calcium in element form is absorbed and the remainder is eliminated in the stool. Calcium is absorbed in the small intestine, the duodenum being the most efficient portion, although most is absorbed in the distal portion of the small intestine, owing to the greater contact time and surface area for absorption. The transport of calcium through the intestine occurs in various stages, all of which are regulated by 1.25(OH)2D3 (Berne and Levy, Fisiologia 3ed;199:823-41). Hypercalcemia is defined as an increase in ionizable calcium or the concentration of total calcium corrected for albumin. It may be classified as mild (total calcium between 10.3 and 11.9 mg/dl), moderate (calcium between 12 and 13.5), or severe (total calcium >13.5).