Feline idiopathic hypercalcemia (Proceedings)


Feline idiopathic hypercalcemia (Proceedings)

Nov 01, 2010

Calcium in circulation occurs in three forms: calcium bound to proteins (approximately 40%), calcium complexed to various anions such as citrate and phosphate (8%), and ionized calcium (iCa, approximately 52%. The latter is the biologically active form of calcium and clinically-relevant hypercalcemia only exists when the ionized fraction of calcium is elevated. Total calcium (bound + complexed + ionized), which is reported on serum biochemical profiles, is influenced by serum protein concentrations, additional circulating complexes (as occurs in CKD), and acid-base status. Formulas to "correct" for serum protein concentrations have been shown to increase diagnostic discordance in both dogs and cats. In the clinically normal animal serum ionized calcium is typically proportional to the level of total calcium. However in the diseased animal serum ionized calcium is not proportional to total serum calcium and total serum calcium measurement cannot be used to predict serum ionized calcium concentration. Ionized calcium measurements are essential to make a diagnosis of hypercalcemia that is dangerous to the patient.

Calcium Homeostasis

The majority of calcium in the body is stored in the bone (>99%) with less than 1% in the extracellular fluid. Ionized calcium must be tightly regulated as it impacts numerous metabolic functions. Parathyroid hormone (PTH), calcitonin, and activated vitamin D (calcitriol) are the major hormonal regulators of calcium uptake, excretion, and storage. The main role of PTH is to increase serum calcium concentration which is achieved mainly by increasing osteoclast activity and release of calcium from bone. PTH also increased renal reabsorption of calcium and promotes phosphorous excretion. PTH also promotes the hydroxylation of 25-hydroxycholecalciferol to 1,25-hydroxycholecalciferol (calcitriol) and a calcitriol deficiency will increase release of PTH. PTH is stimulated by both decreased iCa and increased phosphorous. Calcitonin is released in response to increased iCa. It inhibits osteoclast activity and increases renal excretion of calcium. Calcitonin has limited biological potency. Vitamin D is obtained from food as cholecalciferol and has little biologic activity. It is hydroxylated first in the liver then in the kidney to 1,25-hydroxycholecalciferol (calcitriol), the most biologically active form. Hydroxylation in the kidney is limited by renal α 1 hydroxylase activity. This enzyme is stimulated by PTH and inhibited by hyperphosphatemia and less so by hypercalcemia. Calcitriol promotes intestinal absorption of calcium and phosphorous and at physiologic levels promotes bone calcification. In excessive amounts calcitriol promotes bone reabsorption. Other factors that impact calcium homeostasis include renal, hepatic, and GI function, adrenocortical hormones, thyroid hormone, serum sodium, phosphate, and magnesium concentrations. Bone contains exchangeable calcium for immediate buffering in addition to major storage capacity. The interplay of these systems is complex and complete understanding of calcium homeostasis is still deficient.

Idiopathic Hypercalcemia

Idiopathic hypercalcemia describes cats with hypercalcemia for which no underlying cause can be identified. Many causes of have been speculated including dietary factors (dietary acidification and metabolic acidosis, dietary magnesium restriction, hypervitaminosis D, hypervitaminosis A, and others), a genetic susceptibility, aluminum intoxication, hypoadrenocorticism, an abnormality in the calcium sensing receptor (on the parathyroid gland and the renal collecting tubule), a PTH mimetic, a vitamin D mimetic, a promoter of bone resorption, a stimulator of intestinal calcium absorption, etc and future studies are needed. This syndrome emerged in the early 1990's and has become, in the last decade, the most common cause of ionized hypercalcemia in cats in the United States.

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