Case Study: Hyperparathyroidism in the Keeshond

The skeleton contains approximately 98% of total body calcium. The remaining 2% circulate throughout the body. Calcium is regulated in the healthy mammalian body between approximately 2.20 and 2.60 mmol/L or 9-llmg/dl. A complex relationship exists between the gastrointestinal uptake of calcium, calcium clearance by the kidney and calcium translocation from the small pool in the serum to the large storage area in the bone. Several factors are thought to be important in the regulation of serum calcium. Parathyroid Hormone (PTH) is an 84 amino acid polypeptide produced in the parathyroid glands. PTH secretion is controlled mostly by the level of serum ionized Ca2+. With decreased concentrations of serum Ca2+, PTH secretion is increased. With increased serum Ca2+ concentrations, PTH secretion is decreased. Increased vitamin D concentrations also inhibit PTH secretion. PTH-rp (PTH related peptide) is a PTH like factor with 139-173 amino acids. The N-terminus resembles that ofPTH and is able to bind to PTH receptors in bone and kidney cells. PTH -rp is a normal fetal hormone but is also secreted by neoplastic lymphocytes, carcinoma (anal sac, mammary) and others in humans, dogs and cats. Thus PTH-rp plays an important role in hypercalcemia of malignancy. Vitamin D is a steroid hormone that is obtained through the diet or produced by the action of sunlight on vitamin D precursors in the skin. Calcitriol, the active form of vitamin D, is derived by hydroxylation of the precursor cholecalciferol, first in the liver (25-hydroxylation) and then in the kidney (lhydroxylation). The principal target organ for vitamin D is the gut, where it markedly increases absorption of calcium and phosphorus. It also exerts negative feedback on PTH secretion. Calcitonin is a 32 amino acid hormone produced by the parafollicular C cells of the thyroid. Calcitonin is a weak inhibitor of osteoclastic activity and has some activity in apposing the effects of PTH on the kidney increasing calcium excretion. It is not clear how important these effects are and how efficient calcitonin really is in decreasing serum calcium during hypercalcemia.