Primary hypoparathyroidism in dogs and cats: Physiology, clinical signs, and initial diagnostic tests

To understand this rare condition, you must be familiar with the physiology of calcium regulation. The net effect of a low PTH concentration is hypocalcemia, and the severity of the clinical signs and the timing of their onset are a reflection of the duration and magnitude of the hypocalcemia.
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Jan 01, 2007

Primary hypoparathyroidism is rarely diagnosed in dogs and even less frequently in cats.1-4 It is most commonly caused by the destruction or removal of the parathyroid glands. In dogs, hypoparathyroidism most often results from immune-mediated destruction of the parathyroid glands, but in cats the condition occurs secondary to bilateral thyroidectomy, in which the parathyroid glands were inadvertently removed.1,3,5,6

Animals with primary hypoparathyroidism have decreased production of parathyroid hormone (PTH).3 PTH maintains normal serum calcium and, to some extent, phosphorus concentrations. A lack of PTH results in severe hypocalcemia and mild to moderate hyperphosphatemia through several mechanisms, including decreased bone resorption, decreased renal excretion of phosphate, decreased serum calcitriol (1,25-dihydroxycholecalciferol, or vitamin D3), decreased intestinal absorption of calcium, and increased renal excretion of calcium.1

The neurologic and neuromuscular clinical signs of hypocalcemia do not vary with its cause and are merely supportive in diagnosing hypoparathyroidism.1 While hypocalcemia is not an uncommon laboratory abnormality, hypoparathyroidism is an uncommon cause, so other causes of hypocalcemia must be considered.1,5

SERUM CALCIUM REGULATION

About 99% of the body's total calcium is within the skeleton, about 1% is intracellular, and 0.1% is in the extracellular fluid (i.e. in the plasma).7 In plasma, calcium exists in three forms: about 50% to 60% is ionized (the physiologically active form), about 35% is protein-bound (particularly albumin), and about 10% is complexed (i.e. bound to phosphate, bicarbonate, sulfate, citrate, or lactate).1,7,8 The control of the total serum calcium concentration is so precise that in a healthy animal, the setpoint ranges between 10.5 and 11.5 mg/dl, and the ionized calcium varies less than 0.1 mmol/L in either direction from its setpoint.1,2 The serum calcium concentration is controlled by the interaction among PTH, calcitriol, and calcitonin and their influence on calcium absorption from the intestine, calcium excretion by the kidneys, and uptake and release of calcium from the bone.7,8 PTH is the most important factor in serum calcium regulation.2,9

Because calcium plays an important role in stabilizing the permeability of cell membranes to sodium, hypocalcemia can cause progressive excitation of the nervous system.4,10 Calcium is also essential for normal contraction of skeletal, cardiac, and smooth muscle.7,11 Additionally, precise control of the serum ionized calcium concentration is critical because of calcium's role as an intracellular second messenger, in regulating mitochondrial metabolism, and as a cofactor in the coagulation cascade.4,11

Parathyroid hormone

The only biologically active product of the parathyroid glands is PTH, which is produced by specialized cells called chief cells.1,7 The other cell type in the gland, the oxyphil cell, is rare in carnivores and produces no known active substance.7,12 A pair of parathyroid glands are in close association with each thyroid gland.1,2 In cats, half of each parathyroid pair is embedded within the capsule of the thyroid gland or within the thyroid gland itself.12

PTH is first formed as a preprohormone on the ribosomes of the chief cells.7,9 Within the endoplasmic reticulum and Golgi apparatus, the molecule is cleaved sequentially to the prohormone and then to PTH.7,9 PTH is subsequently packaged into secretory granules within the cytoplasm.7 Within the chief cells of the parathyroid gland, a calcium-sensing receptor enables the chief cells to act as sensors of the extracellular calcium concentration.9 The serum ionized calcium provides proportional feedback, inhibiting or stimulating the release of PTH.1,2,7,9,12 Although less physiologically important, calcitriol also inhibits the production and release of PTH.9